Materiały źródłowe

• #1 Alkaptonuria (Black Urine Disease): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/941530-overview

  Alkaptonuria, also called black urine disease, alcaptonuria, and black bone disease, is one of 4 disorders originally defined as an inborn error of metabolism by Archibald Garrod in his Croonian Lectures of 1902. The earliest sign of the disorder is the tendency for diapers to stain black. Throughout childhood and most of early adulthood, an asymptomatic, slowly progressive deposition of pigmentlike polymer material into collagenous tissues occurs. […] In the fourth decade of life, external signs of pigment deposition, called ochronosis, begin to appear. The slate blue, gray, or black discoloration of sclerae and ear cartilage is indicative of widespread staining of the body tissues, particularly cartilage. The hips, knees, and intervertebral joints are affected most commonly and show clinical symptoms resembling rheumatoid arthritis.

• #2 Orphanet: Alkaptonuria

  https://www.orpha.net/en/disease/detail/56

  A rare disorder of phenylalanine and tyrosine metabolism characterized by the accumulation of homogentisic acid (HGA) and its oxidized product, benzoquinone acetic acid (BQA), in various tissues (e.g. cartilage, connective tissue) and body fluids (urine, sweat), causing urine to darken when exposed to air as well as grey-blue coloration of the sclera and ear helix (ochronosis), and a disabling joint disease involving both the axial and peripheral joints (ochronotic arthropathy). […] Many affected individuals are asymptomatic and unaware of their condition until adulthood, however, homogentisic aciduria may be recognized early in infancy by dark-stained diapers. After the third decade, unusual pigmentation of the sclera and the skin overlying cartilage begins to be observed, as well as muscular-skeletal symptoms such as back pain and stiffness. Involvement of the large peripheral joints usually occurs several years after spinal changes, often leading to end-stage joint disease. Ochronotic peripheral arthropathy is generally degenerative in nature. From the fourth decade, joint mobility diminishes. Ankylosis may be present. Fractures of the vertebrae and long bones are also possible. Other features may include genitourinary (e.g. renal, bladder, prostatic stones) and cardiac (mitral valvulitis, arrhythmias) complications as well as respiratory insufficiency due to musculoskeletal involvement.

• #3 Alkaptonuria | About the Disease | GARD

  https://rarediseases.info.nih.gov/diseases/5775/alkaptonuria

  Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air. The three major features of Alkaptonuria are the presence of dark urine, ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, and arthritis of the spine and larger joints. Other features of this condition can include heart problems, kidney stones, and prostate stones. […] Symptoms of this disease may start to appear as an Infant and as an Adult. […] The types of symptoms experienced, and their intensity, may vary among people with this disease. Your experience may be different from others. […] Symptoms may start to appear as an Infant and as an Adult.

• #4 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Alkaptonuria.aspx

  The three major features of alkaptonuria include: […] Homogentisic acid in the urine, which is oxidized by air to benzoquinoneacetate polymers and causes darkening of the urine on standing. This may be noticed in infants and leads to the diagnosis of this disorder in childhood in a fifth of cases. […] Ochronosis or bluish-black pigmentation of connective tissue occurs, usually after the age of 30, and is apparent as discoloration of the ears and eyes as well as of various body fluids. […] Arthritis involving the spine as well as large joints occurs, typically in the twenties, because of the deposition of the polymer within the cartilage and subchondral bone. This typically causes severe and progressive discoloration of the joint, which may lead to disability. […] Other features may also arise, including: Calcification or regurgitation of the mitral and aortic valve, aortic dilatation, renal calculi, and prostate stones.

• #5 Alkaptonuria

  https://www.nhs.uk/conditions/alkaptonuria/

  One of the earliest signs of the condition is dark-stained nappies, as homogentisic acid causes urine to turn black when exposed to air for a few hours. […] If this sign is missed or overlooked in a baby or child, the disorder may go unnoticed until adulthood, as there are usually no other noticeable symptoms until the person reaches their late 20s to early 30s. […] Over the course of many years, homogentisic acid slowly builds up in tissues throughout the body. […] When a person with alkaptonuria reaches their 30s, they may start to experience joint problems. […] Typically, they’ll have lower back pain and stiffness, followed by knee, hip and shoulder pain. […] Eventually, cartilage a tough, flexible tissue found throughout the body may become brittle and break, leading to joint and spinal damage.

• #6 Alkaptonuria: Causes, Symptoms and Diagnosis

  https://www.healthline.com/health/alkaptonuria

  Alkaptonuria is a lifelong condition, but there are many ways to help manage your symptoms. […] Symptoms become more obvious as you age. […] Your urine may turn dark brown or black when its exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis. […] For example, you may notice chronic stiffness or pain in your lower back or large joints. […] Other symptoms of alkaptonuria include: dark spots in the sclera (white) of your eyes, thickened and darkened cartilage in your ears, blue speckled discoloration of your skin, particularly around sweat glands, dark-colored sweat or sweat stains, black earwax, kidney stones and prostate stones, arthritis (especially hip and knee joints). […] Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. This can keep them from closing properly, resulting in aortic and mitral valve disorders.

• #7 What Happens in Alkaptonuria?

  https://www.medicinenet.com/what_happens_in_alkaptonuria/article.htm

  Alkaptonuria is a rare inherited disorder that prevents the body from fully breaking down two amino acids: tyrosine and phenylalanine. […] One of the earliest signs of this condition is dark-stained nappies because homogentisic acid causes the urine to turn black when exposed to air for a few hours. If this sign is missed or overlooked, the disorder may go unnoticed until adulthood because there are usually no other noticeable symptoms until the person reaches their late 20s to early 30s. Other signs and symptoms may include: […] Darkening of the ear (or other parts of the skin) (An obvious sign of alkaptonuria in adults is thickening and blue-black discoloration of the ear cartilage. This is called ochronosis. The earwax may also be black or reddish-brown.) […] Deposits of homogentisic acid around the heart valves can cause them to harden and turn brittle and black (The blood vessels can also stiffen and weaken, and this can lead to heart disease and may require heart valve replacements.)

• #8 Alkaptonuria and ochronosis

  https://dermnetnz.org/topics/alkaptonuria-and-ochronosis

  Alkaptonuria is a rare genetic disease that is characterised by passing urine that becomes black when left standing. The earliest sign of the condition is usually dark staining found in nappies or diapers of infants. […] The most obvious sign in adults is a thickening and blue-black discolouration of the ear cartilage. This blue-black discolouration of connective tissue (including bone, cartilage, and skin) caused by deposits of yellow or ochre-coloured pigment is called ochronosis. […] Most patients don’t have any symptoms throughout childhood or early adult life and it is not until they reach their 40’s that other signs of the disease start appearing. One of the earliest signs is thickening of the ear cartilage (the pinna feels noticeably thickened and flexible). In addition the skin turns a blue-black colour. Earwax is often reddish-brown or jet-black. Gradually patients will suffer sore joints, leading to arthropathy (joint disease characterised by swelling and enlarged bones). Many body parts become affected due to the build-up of pigment deposits in bones and cartilage.

• #9 Alkaptonuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/alkaptonuria/

  Alkaptonuria is an inherited condition that causes arthritis, kidney stones, spots of dark pigmentation, and dark urine. Ochronosis, a buildup of dark (blue-black) pigment in certain tissues, is a characteristic feature of alkaptonuria. The first symptom of alkaptonuria is often urine that turns black or very dark when it is exposed to air (oxidation). However, this color change may not occur immediately after urination. […] Ochronosis in the joints causes people with alkaptonuria to develop arthritis, typically in early adulthood. Arthritis usually affects the spine and large joints (such as the hips and knees). Many affected individuals require joint replacements later in life. […] Over time, the deposits of pigment can harden (calcify). Calcification in joints or ligaments causes them to become rigid and brittle, decreasing their flexibility and making them prone to damage.

• #10 Chromosome 3: gene associated with alkaptonuria, Matt Ridley :: CSHL DNA Learning Center

  https://dnalc.cshl.edu/view/15398-Chromosome-3-gene-associated-with-alkaptonuria-Matt-Ridley.html

  Mutations in the HGD gene can cause the rare disorder alkaptonuria. […] The homogentisic acid builds up and causes symptoms of alkaptonuria that include arthritis, black urine and reddish earwax. […] It’s a gene associated with a disease called alkaptonuria, which turns urine black and earwax red.

• #11

  https://byjus.com/neet/alkaptonuria-notes/

  Alkaptonuria is an inherited condition that does not develop symptoms until about 30 years. They are due to the chronic assemblage of homogentisic acid within the connective tissue, mainly the cartilage. […] The dark stains on a babys diaper are among the earliest signs of alkaptonuria and are present from birth. There are few other symptoms during childhood, which become more evident with age. […] Other symptoms of alkaptonuria include: Arthritis, Black earwax, Prostate and kidney stones, Signs of early-onset osteoarthritis, Dark spots in the sclera of the eyes, Dark-coloured sweat or sweat stains, Thickened and darkened cartilage in the ears, Chronic stiffness or pain in your lower back or large joints, Blue speckled discolouration of the skin, particularly around sweat glands, Shortness of breath or difficulty in breathing is caused due to the stiffness of bones and muscles around the lungs, and it prevents the chest from expanding.

• #12 Alkaptonuria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560571/

  Ochronosis commonly presents in the third or fourth decade, which develops as the deposition of benzoquinone acetate in both extra- and intra-cellularly connective tissue. Finally, ochronotic arthropathy develops as an accumulation of Homogentisinic acid polymer within hyaline articular cartilage. […] The pathological effects of ochronosis include arthritis, increased incidence of renal, prostatic, gall bladder stones, ruptures of muscle, tendons, and ligaments. […] This disorder does not seem to affect life expectancy. However, the significant impact is on the patient’s quality of life; for example, lots of people with AKU have experienced symptoms such as lack of sleep, pain, and difficulty breathing. These features begin in the fourth decade.

• #13 Alkaptonuria (Black Urine Disease): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/941530-overview

  Alkaptonuria, also called black urine disease, alcaptonuria, and black bone disease, is one of 4 disorders originally defined as an inborn error of metabolism by Archibald Garrod in his Croonian Lectures of 1902. The earliest sign of the disorder is the tendency for diapers to stain black. Throughout childhood and most of early adulthood, an asymptomatic, slowly progressive deposition of pigmentlike polymer material into collagenous tissues occurs. […] In the fourth decade of life, external signs of pigment deposition, called ochronosis, begin to appear. The slate blue, gray, or black discoloration of sclerae and ear cartilage is indicative of widespread staining of the body tissues, particularly cartilage. The hips, knees, and intervertebral joints are affected most commonly and show clinical symptoms resembling rheumatoid arthritis.

• #14 Alkaptonuria: Causes, Symptoms and Diagnosis

  https://www.healthline.com/health/alkaptonuria

  Alkaptonuria is a lifelong condition, but there are many ways to help manage your symptoms. […] Symptoms become more obvious as you age. […] Your urine may turn dark brown or black when its exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis. […] For example, you may notice chronic stiffness or pain in your lower back or large joints. […] Other symptoms of alkaptonuria include: dark spots in the sclera (white) of your eyes, thickened and darkened cartilage in your ears, blue speckled discoloration of your skin, particularly around sweat glands, dark-colored sweat or sweat stains, black earwax, kidney stones and prostate stones, arthritis (especially hip and knee joints). […] Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. This can keep them from closing properly, resulting in aortic and mitral valve disorders.

• #15 Alkaptonuria

  https://www.nhs.uk/conditions/alkaptonuria/

  Many people develop brown or black spots on the whites of their eyes. […] Another sign in many adults with alkaptonuria is thickening of ear cartilage. […] Alkaptonuria can result in discoloured sweat, which can stain clothes and cause some people to have blue or black speckled areas of skin. […] If the bones and muscles around the lungs become stiff, it can prevent the chest expanding and lead to shortness of breath or difficulty breathing. […] Deposits of homogentisic acid around heart valves can cause them to narrow, harden and turn brittle and black. […] This can lead to heart disease and may require heart valve replacements. […] Alkaptonuria is a lifelong condition. […] Painkillers and lifestyle changes may help you cope with the symptoms. […] People with alkaptonuria have a normal life expectancy. However, they will eventually experience symptoms, such as pain and loss of movement in the joints and spine, which can affect quality of life.

• #16 Alkaptonuria: Causes, Symptoms and Diagnosis

  https://www.healthline.com/health/alkaptonuria

  Alkaptonuria is a lifelong condition, but there are many ways to help manage your symptoms. […] Symptoms become more obvious as you age. […] Your urine may turn dark brown or black when its exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis. […] For example, you may notice chronic stiffness or pain in your lower back or large joints. […] Other symptoms of alkaptonuria include: dark spots in the sclera (white) of your eyes, thickened and darkened cartilage in your ears, blue speckled discoloration of your skin, particularly around sweat glands, dark-colored sweat or sweat stains, black earwax, kidney stones and prostate stones, arthritis (especially hip and knee joints). […] Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. This can keep them from closing properly, resulting in aortic and mitral valve disorders.

• #17 Alkaptonuria

  https://www.nhs.uk/conditions/alkaptonuria/

  Many people develop brown or black spots on the whites of their eyes. […] Another sign in many adults with alkaptonuria is thickening of ear cartilage. […] Alkaptonuria can result in discoloured sweat, which can stain clothes and cause some people to have blue or black speckled areas of skin. […] If the bones and muscles around the lungs become stiff, it can prevent the chest expanding and lead to shortness of breath or difficulty breathing. […] Deposits of homogentisic acid around heart valves can cause them to narrow, harden and turn brittle and black. […] This can lead to heart disease and may require heart valve replacements. […] Alkaptonuria is a lifelong condition. […] Painkillers and lifestyle changes may help you cope with the symptoms. […] People with alkaptonuria have a normal life expectancy. However, they will eventually experience symptoms, such as pain and loss of movement in the joints and spine, which can affect quality of life.

• #18 Alkaptonuria: Causes, Symptoms and Diagnosis

  https://www.healthline.com/health/alkaptonuria

  Alkaptonuria is a lifelong condition, but there are many ways to help manage your symptoms. […] Symptoms become more obvious as you age. […] Your urine may turn dark brown or black when its exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis. […] For example, you may notice chronic stiffness or pain in your lower back or large joints. […] Other symptoms of alkaptonuria include: dark spots in the sclera (white) of your eyes, thickened and darkened cartilage in your ears, blue speckled discoloration of your skin, particularly around sweat glands, dark-colored sweat or sweat stains, black earwax, kidney stones and prostate stones, arthritis (especially hip and knee joints). […] Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. This can keep them from closing properly, resulting in aortic and mitral valve disorders.

• #19 Alkaptonuria and ochronosis

  https://dermnetnz.org/topics/alkaptonuria-and-ochronosis

  Bones and cartilage of the lower back, knees, shoulders and hips are most affected. Firstly patients suffer low back pain with stiffness, followed by knee, shoulder and hip pain over the next 10 years. Cartilage becomes brittle and can break apart easily. In some cases this leads to spinal injuries such as prolapsed intervertebral discs. […] Deposits around the trachea (windpipe), larynx (voice box) and bronchi (air passages to the lungs) may cause shortness of breath and difficulty breathing. […] Deposits around the heart and blood vessels can calcify (harden) and lead to atherosclerotic plaques (hard spots in arteries). […] Pigmentation of the sclera of the eye usually occurs early on. This does not affect vision but appears as brown or grey deposits on the surface of the eye. […] Skin colour changes are most apparent on areas exposed to the sun and where sweat glands are found. Areas most affected include the cheeks, forehead, armpits and genital regions. The skin takes on a blue-black speckled discolouration. Sweat produced has been found to stain clothes. Sometimes nails can be affected and turn a distinct brown colour. […] Life expectancy is normal although patients may be at increased risk of heart conditions and may require surgical treatments for spine, hip, knee and shoulder joint problems.

• #20 Alkaptonuria: Causes, Symptoms and Diagnosis

  https://www.healthline.com/health/alkaptonuria

  Alkaptonuria is a lifelong condition, but there are many ways to help manage your symptoms. […] Symptoms become more obvious as you age. […] Your urine may turn dark brown or black when its exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis. […] For example, you may notice chronic stiffness or pain in your lower back or large joints. […] Other symptoms of alkaptonuria include: dark spots in the sclera (white) of your eyes, thickened and darkened cartilage in your ears, blue speckled discoloration of your skin, particularly around sweat glands, dark-colored sweat or sweat stains, black earwax, kidney stones and prostate stones, arthritis (especially hip and knee joints). […] Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. This can keep them from closing properly, resulting in aortic and mitral valve disorders.

• #21 Alkaptonuria

  https://www.nhs.uk/conditions/alkaptonuria/

  Many people develop brown or black spots on the whites of their eyes. […] Another sign in many adults with alkaptonuria is thickening of ear cartilage. […] Alkaptonuria can result in discoloured sweat, which can stain clothes and cause some people to have blue or black speckled areas of skin. […] If the bones and muscles around the lungs become stiff, it can prevent the chest expanding and lead to shortness of breath or difficulty breathing. […] Deposits of homogentisic acid around heart valves can cause them to narrow, harden and turn brittle and black. […] This can lead to heart disease and may require heart valve replacements. […] Alkaptonuria is a lifelong condition. […] Painkillers and lifestyle changes may help you cope with the symptoms. […] People with alkaptonuria have a normal life expectancy. However, they will eventually experience symptoms, such as pain and loss of movement in the joints and spine, which can affect quality of life.

• #22 Alkaptonuria and ochronosis

  https://dermnetnz.org/topics/alkaptonuria-and-ochronosis

  Bones and cartilage of the lower back, knees, shoulders and hips are most affected. Firstly patients suffer low back pain with stiffness, followed by knee, shoulder and hip pain over the next 10 years. Cartilage becomes brittle and can break apart easily. In some cases this leads to spinal injuries such as prolapsed intervertebral discs. […] Deposits around the trachea (windpipe), larynx (voice box) and bronchi (air passages to the lungs) may cause shortness of breath and difficulty breathing. […] Deposits around the heart and blood vessels can calcify (harden) and lead to atherosclerotic plaques (hard spots in arteries). […] Pigmentation of the sclera of the eye usually occurs early on. This does not affect vision but appears as brown or grey deposits on the surface of the eye. […] Skin colour changes are most apparent on areas exposed to the sun and where sweat glands are found. Areas most affected include the cheeks, forehead, armpits and genital regions. The skin takes on a blue-black speckled discolouration. Sweat produced has been found to stain clothes. Sometimes nails can be affected and turn a distinct brown colour. […] Life expectancy is normal although patients may be at increased risk of heart conditions and may require surgical treatments for spine, hip, knee and shoulder joint problems.

• #23 Alkaptonuria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560571/

  Ochronosis commonly presents in the third or fourth decade, which develops as the deposition of benzoquinone acetate in both extra- and intra-cellularly connective tissue. Finally, ochronotic arthropathy develops as an accumulation of Homogentisinic acid polymer within hyaline articular cartilage. […] The pathological effects of ochronosis include arthritis, increased incidence of renal, prostatic, gall bladder stones, ruptures of muscle, tendons, and ligaments. […] This disorder does not seem to affect life expectancy. However, the significant impact is on the patient’s quality of life; for example, lots of people with AKU have experienced symptoms such as lack of sleep, pain, and difficulty breathing. These features begin in the fourth decade.

• #24 Alkaptonuria: Causes, Symptoms

  https://www.brainkart.com/article/Alkaptonuria–Causes,-Symptoms_26717/

  Homogentisic acid accumulates in the tissues and blood and also appears in urine. Most striking clinical manifestation is occurrence of dark urine on standing in air. Homogentisic acid like many derivatives of tyrosine is readily oxidized to black pigments. These pigments are called as alkaptons. Urine in an exposed air slowly turns black from top to bottom. […] In long standing cases, deposition of homogentisic acid derivatives in cartilages of ears and other exposed places leading to generalized pigmentation of connective tissues and deposition in joints leading to arthritis, a condition is called ochronosis. This is due to the of oxidation homogentisate by polyphenol oxidase, forming benzoquinone acetate, which polymerizes and binds to connective tissue macromolecules.

• #25 Alkaptonuria: Causes, Symptoms

  https://www.brainkart.com/article/Alkaptonuria–Causes,-Symptoms_26717/

  Homogentisic acid accumulates in the tissues and blood and also appears in urine. Most striking clinical manifestation is occurrence of dark urine on standing in air. Homogentisic acid like many derivatives of tyrosine is readily oxidized to black pigments. These pigments are called as alkaptons. Urine in an exposed air slowly turns black from top to bottom. […] In long standing cases, deposition of homogentisic acid derivatives in cartilages of ears and other exposed places leading to generalized pigmentation of connective tissues and deposition in joints leading to arthritis, a condition is called ochronosis. This is due to the of oxidation homogentisate by polyphenol oxidase, forming benzoquinone acetate, which polymerizes and binds to connective tissue macromolecules.

• #26 Alkaptonuria

  https://www.nhs.uk/conditions/alkaptonuria/

  One of the earliest signs of the condition is dark-stained nappies, as homogentisic acid causes urine to turn black when exposed to air for a few hours. […] If this sign is missed or overlooked in a baby or child, the disorder may go unnoticed until adulthood, as there are usually no other noticeable symptoms until the person reaches their late 20s to early 30s. […] Over the course of many years, homogentisic acid slowly builds up in tissues throughout the body. […] When a person with alkaptonuria reaches their 30s, they may start to experience joint problems. […] Typically, they’ll have lower back pain and stiffness, followed by knee, hip and shoulder pain. […] Eventually, cartilage a tough, flexible tissue found throughout the body may become brittle and break, leading to joint and spinal damage.

• #27 Alkaptonuria: Causes, Symptoms and Diagnosis

  https://www.healthline.com/health/alkaptonuria

  Alkaptonuria is a lifelong condition, but there are many ways to help manage your symptoms. […] Symptoms become more obvious as you age. […] Your urine may turn dark brown or black when its exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis. […] For example, you may notice chronic stiffness or pain in your lower back or large joints. […] Other symptoms of alkaptonuria include: dark spots in the sclera (white) of your eyes, thickened and darkened cartilage in your ears, blue speckled discoloration of your skin, particularly around sweat glands, dark-colored sweat or sweat stains, black earwax, kidney stones and prostate stones, arthritis (especially hip and knee joints). […] Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. This can keep them from closing properly, resulting in aortic and mitral valve disorders.

• #28 Alkaptonuria: Causes, Symptoms & Treatment Options

  https://sehathub.com/alkaptonuria

  Long-term alkaptonuria notably brings on chronic joint pain and inflammation (arthritis), primarily affecting the spine and major joints, resulting in ochronotic arthropathy. Severe arthritis can be incapacitating. Common symptoms include low back pain and stiffness, which can occur before age 30. […] Ankylosis, which refers to the abnormal stiffening and immobility of a joint due to fusion of the bones, can occur in individuals with alkaptonuria. This condition often leads to lumbar discomfort and arthritis, resulting in joint effusions, reduced joint movement, and decreased spinal and thoracic mobility, which can cause significant disability. Additionally, osteopenia, or reduced bone density, increases the risk of fractures in affected individuals.

• #29 Alkaptonuria (Black Urine Disease) – Causes, Symptoms, Diagnosis, Treatment and Prognosis

  https://www.medindia.net/health/conditions/alkaptonuria.htm

  Kidney Prostate Stones: Kidney stones can develop in 50% of affected individuals over 64 years of age. Men with alkaptonuria may also develop prostate stones. Passage of these black stones can be extremely painful. […] Ochronotic Arthropathy: There can be chronic joint pain and inflammation (arthritis). When the spine and large joints such as the hips and knees are affected, it is technically termed as ochronotic arthropathy. […] Ankylosis Kyphosis: Intervertebral discs can flatten, calcify and eventually fuse. This can result in ankylosis, (a condition where the affected joints become stiff and immobile). Moreover, kyphosis or hunchback may occur, where there is an excessive convex curvature of the spine. […] Stiffening of Heart Valves: Accumulation of HGA within the aortic or mitral valves can cause thickening of the valves and narrowing (stenosis) of their openings due to calcification. In some cases, calcification of the coronary blood vessels may also occur.

• #30 Alkaptonuria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560571/

  Alkaptonuria is a rare genetic inborn error of protein metabolism. Most of the time, diagnosis is delayed as the patient remains asymptomatic during childhood. If treatment also delays, it leads to severe deformity of joints, spine, and organ dysfunction. Early diagnosis is the key to managing alkaptonuria effectively. […] The typical presentation of alkaptonuria is the darkening of the urine upon standing for longer time or dark urine stains on the diaper to the oxidation and polymerization of homogentisic acid; this could be the only feature suggestive of alkaptonuria in the pediatric age group. A significant amount of people with AKU may not present with black urine, which can be unreliable. The most frequent symptoms are one of the arthritic features confined mainly to the spine, hips, and knees. Practically all people with AKU eventually experience Arthritis. The onset of lumbar back pain, thoracic back pain, or both is frequent, especially around age 30. Progressive kyphoscoliosis, reduced disc space, spinal stenosis, and compressive myelopathy can occur with advancing age.

• #31 Alkaptonuria (Black Urine Disease): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/941530-overview

  Life expectancy is normal; however, associated morbidity can be significant. Early involvement of the intervertebral discs at the thoracic and lumbar levels is very common, occurring in approximately 50% of affected individuals. Typically, significant back pain begins from age 30 years. The large joints (knee, shoulder and hip) are very frequently involved; at least half of all patients undergo joint replacement by the middle of the sixth decade of life. […] Because alkaptonuria is a genetic disorder, the deficiency of the HGO enzyme is present from conception. Clinical symptoms, aside from dark-stained diapers, are generally present only after the third decade of life.

• #32 Alkaptonuria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560571/

  Alkaptonuria is a rare genetic inborn error of protein metabolism. Most of the time, diagnosis is delayed as the patient remains asymptomatic during childhood. If treatment also delays, it leads to severe deformity of joints, spine, and organ dysfunction. Early diagnosis is the key to managing alkaptonuria effectively. […] The typical presentation of alkaptonuria is the darkening of the urine upon standing for longer time or dark urine stains on the diaper to the oxidation and polymerization of homogentisic acid; this could be the only feature suggestive of alkaptonuria in the pediatric age group. A significant amount of people with AKU may not present with black urine, which can be unreliable. The most frequent symptoms are one of the arthritic features confined mainly to the spine, hips, and knees. Practically all people with AKU eventually experience Arthritis. The onset of lumbar back pain, thoracic back pain, or both is frequent, especially around age 30. Progressive kyphoscoliosis, reduced disc space, spinal stenosis, and compressive myelopathy can occur with advancing age.

• #33 Alkaptonuria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560571/

  Alkaptonuria is a rare genetic inborn error of protein metabolism. Most of the time, diagnosis is delayed as the patient remains asymptomatic during childhood. If treatment also delays, it leads to severe deformity of joints, spine, and organ dysfunction. Early diagnosis is the key to managing alkaptonuria effectively. […] The typical presentation of alkaptonuria is the darkening of the urine upon standing for longer time or dark urine stains on the diaper to the oxidation and polymerization of homogentisic acid; this could be the only feature suggestive of alkaptonuria in the pediatric age group. A significant amount of people with AKU may not present with black urine, which can be unreliable. The most frequent symptoms are one of the arthritic features confined mainly to the spine, hips, and knees. Practically all people with AKU eventually experience Arthritis. The onset of lumbar back pain, thoracic back pain, or both is frequent, especially around age 30. Progressive kyphoscoliosis, reduced disc space, spinal stenosis, and compressive myelopathy can occur with advancing age.

• #34 Alkaptonuria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560571/

  Alkaptonuria is a rare genetic inborn error of protein metabolism. Most of the time, diagnosis is delayed as the patient remains asymptomatic during childhood. If treatment also delays, it leads to severe deformity of joints, spine, and organ dysfunction. Early diagnosis is the key to managing alkaptonuria effectively. […] The typical presentation of alkaptonuria is the darkening of the urine upon standing for longer time or dark urine stains on the diaper to the oxidation and polymerization of homogentisic acid; this could be the only feature suggestive of alkaptonuria in the pediatric age group. A significant amount of people with AKU may not present with black urine, which can be unreliable. The most frequent symptoms are one of the arthritic features confined mainly to the spine, hips, and knees. Practically all people with AKU eventually experience Arthritis. The onset of lumbar back pain, thoracic back pain, or both is frequent, especially around age 30. Progressive kyphoscoliosis, reduced disc space, spinal stenosis, and compressive myelopathy can occur with advancing age.

• #35 Alkaptonuria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560571/

  Alkaptonuria is a rare genetic inborn error of protein metabolism. Most of the time, diagnosis is delayed as the patient remains asymptomatic during childhood. If treatment also delays, it leads to severe deformity of joints, spine, and organ dysfunction. Early diagnosis is the key to managing alkaptonuria effectively. […] The typical presentation of alkaptonuria is the darkening of the urine upon standing for longer time or dark urine stains on the diaper to the oxidation and polymerization of homogentisic acid; this could be the only feature suggestive of alkaptonuria in the pediatric age group. A significant amount of people with AKU may not present with black urine, which can be unreliable. The most frequent symptoms are one of the arthritic features confined mainly to the spine, hips, and knees. Practically all people with AKU eventually experience Arthritis. The onset of lumbar back pain, thoracic back pain, or both is frequent, especially around age 30. Progressive kyphoscoliosis, reduced disc space, spinal stenosis, and compressive myelopathy can occur with advancing age.

• #36 Alkaptonuria: Causes, Symptoms & Treatment Options

  https://sehathub.com/alkaptonuria

  Moreover, heart issues might potentially result from alkaptonuria. […] Grey discoloration may be found in the sclerae or ear cartilage. Calcifications may be palpable in the discolored areas, particularly in the cartilage of the ear. Joint mobility diminishes, as in osteoarthritis. Spontaneous fusion of one or more discs may occur, with consequent diminished spinal flexion. Joint effusions, particularly in the knee, are common, and the range of motion may be significantly diminished. […] Life expectancy is normal; however, associated morbidity can be significant. Early involvement of the intervertebral discs at the thoracic and lumbar levels is very common. Typically, significant back pain begins at the age of 30 years. It frequently involves the large joints (knee, shoulder, and hip); at least half of all patients undergo joint replacement by the middle of the sixth decade of life.

• #37 Alkaptonuria | Doctor

  https://patient.info/doctor/alkaptonuria.htm

  Symptoms of arthritis in the spine, hips and knees, starting around the age of 30 are common, if not universal. […] In the fourth decade of life, signs of pigment deposition called ochronosis begin. The slate blue, grey, or black discoloration of sclerae and ear cartilage is characteristic of widespread staining of the body tissues but, particularly, cartilage. Hips, knees and intervertebral discs are most affected and the disease may resemble rheumatoid arthritis (RA); however, calcification in these sites gives a radiological picture that is more consistent with osteoarthritis (OA). Calcification may be palpable, especially in the pinna. Joint mobility declines and ankylosis may occur, especially in the spine with fusion of one or more discs. Disc herniation may occur. Joint effusions, especially in the knee are common and range of movement is restricted. Pigmentation of joints and tendons may be noticed at operation. There may be disease of the mitral or aortic valves and calcification of coronary arteries. […] Life expectancy is normal but there is considerable morbidity, with significant pain beginning as early as the age of 30. Slow degeneration of the spinal discs and the large joints are the main problems, with subsequent loss of agility and mobility.

• #38 Alkaptonuria: Causes, Symptoms & Treatment Options

  https://sehathub.com/alkaptonuria

  Moreover, heart issues might potentially result from alkaptonuria. […] Grey discoloration may be found in the sclerae or ear cartilage. Calcifications may be palpable in the discolored areas, particularly in the cartilage of the ear. Joint mobility diminishes, as in osteoarthritis. Spontaneous fusion of one or more discs may occur, with consequent diminished spinal flexion. Joint effusions, particularly in the knee, are common, and the range of motion may be significantly diminished. […] Life expectancy is normal; however, associated morbidity can be significant. Early involvement of the intervertebral discs at the thoracic and lumbar levels is very common. Typically, significant back pain begins at the age of 30 years. It frequently involves the large joints (knee, shoulder, and hip); at least half of all patients undergo joint replacement by the middle of the sixth decade of life.

• #39 Alkaptonuria | Doctor

  https://patient.info/doctor/alkaptonuria.htm

  Symptoms of arthritis in the spine, hips and knees, starting around the age of 30 are common, if not universal. […] In the fourth decade of life, signs of pigment deposition called ochronosis begin. The slate blue, grey, or black discoloration of sclerae and ear cartilage is characteristic of widespread staining of the body tissues but, particularly, cartilage. Hips, knees and intervertebral discs are most affected and the disease may resemble rheumatoid arthritis (RA); however, calcification in these sites gives a radiological picture that is more consistent with osteoarthritis (OA). Calcification may be palpable, especially in the pinna. Joint mobility declines and ankylosis may occur, especially in the spine with fusion of one or more discs. Disc herniation may occur. Joint effusions, especially in the knee are common and range of movement is restricted. Pigmentation of joints and tendons may be noticed at operation. There may be disease of the mitral or aortic valves and calcification of coronary arteries. […] Life expectancy is normal but there is considerable morbidity, with significant pain beginning as early as the age of 30. Slow degeneration of the spinal discs and the large joints are the main problems, with subsequent loss of agility and mobility.

• #40 Alkaptonuria

  https://www.nhs.uk/conditions/alkaptonuria/

  One of the earliest signs of the condition is dark-stained nappies, as homogentisic acid causes urine to turn black when exposed to air for a few hours. […] If this sign is missed or overlooked in a baby or child, the disorder may go unnoticed until adulthood, as there are usually no other noticeable symptoms until the person reaches their late 20s to early 30s. […] Over the course of many years, homogentisic acid slowly builds up in tissues throughout the body. […] When a person with alkaptonuria reaches their 30s, they may start to experience joint problems. […] Typically, they’ll have lower back pain and stiffness, followed by knee, hip and shoulder pain. […] Eventually, cartilage a tough, flexible tissue found throughout the body may become brittle and break, leading to joint and spinal damage.

• #41 Alkaptonuria: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001200.htm

  Alkaptonuria is a rare condition in which a person’s urine turns a dark brownish-black color when exposed to air. […] Symptoms may include: […] Urine in an infant’s diaper may darken and can turn almost black after several hours. However, many people with this condition may not know they have it. The disease is most often discovered in mid-adulthood (around age 40), when joint and other problems occur. […] Arthritis (especially of the spine) that gets worse over time. […] Darkening of the ear. […] Dark spots on the white of the eye and cornea. […] The build-up of homogentisic acid in the cartilage causes arthritis in many adults with alkaptonuria.

• #42 Alkaptonuria (Black Urine Disease) – Causes, Symptoms, Diagnosis, Treatment and Prognosis

  https://www.medindia.net/health/conditions/alkaptonuria.htm

  Kidney Prostate Stones: Kidney stones can develop in 50% of affected individuals over 64 years of age. Men with alkaptonuria may also develop prostate stones. Passage of these black stones can be extremely painful. […] Ochronotic Arthropathy: There can be chronic joint pain and inflammation (arthritis). When the spine and large joints such as the hips and knees are affected, it is technically termed as ochronotic arthropathy. […] Ankylosis Kyphosis: Intervertebral discs can flatten, calcify and eventually fuse. This can result in ankylosis, (a condition where the affected joints become stiff and immobile). Moreover, kyphosis or hunchback may occur, where there is an excessive convex curvature of the spine. […] Stiffening of Heart Valves: Accumulation of HGA within the aortic or mitral valves can cause thickening of the valves and narrowing (stenosis) of their openings due to calcification. In some cases, calcification of the coronary blood vessels may also occur.

• #43 Alkaptonuria | Hereditary Ocular Diseases

  https://disorders.eyes.arizona.edu/disorders/alkaptonuria

  Ochronosis (dark pigmentation in connective tissue) as the result of homogentisic acid (HGA) accumulation is a useful sign but does not appear until the 4th decade. As a result the joint cartilage becomes fragile leading to disabling and chronic symptoms of arthritis especially in the spine and large joints. Symptoms usually begin in the third or fourth decade and the degeneration of the ochronotic intervertebral disks may result in significant loss of height. Back pain, kyphosis, and decreased lumbar flexion are common. […] Tendons, ligaments, and other fibrous tissue such as sclerae and heart valves are all susceptible to degenerative changes. The discoloration in skin hue can also be seen in the axillae, nail beds, pinnae, forehead, tympanic membranes, genital areas, and buccal mucosa. Clothing may become stained from discolored perspiration. […] HGA in the urine oxidizes and turns dark and parents may note staining of diapers in the newborn period. The urine also becomes alkaline. Plasma levels of HGA are also elevated. Urolithiasis may occur.

• #44 Alkaptonuria: Causes, Symptoms and Diagnosis

  https://www.healthline.com/health/alkaptonuria

  Alkaptonuria is a lifelong condition, but there are many ways to help manage your symptoms. […] Symptoms become more obvious as you age. […] Your urine may turn dark brown or black when its exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis. […] For example, you may notice chronic stiffness or pain in your lower back or large joints. […] Other symptoms of alkaptonuria include: dark spots in the sclera (white) of your eyes, thickened and darkened cartilage in your ears, blue speckled discoloration of your skin, particularly around sweat glands, dark-colored sweat or sweat stains, black earwax, kidney stones and prostate stones, arthritis (especially hip and knee joints). […] Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. This can keep them from closing properly, resulting in aortic and mitral valve disorders.

• #45 Alkaptonuria and ochronosis

  https://dermnetnz.org/topics/alkaptonuria-and-ochronosis

  Bones and cartilage of the lower back, knees, shoulders and hips are most affected. Firstly patients suffer low back pain with stiffness, followed by knee, shoulder and hip pain over the next 10 years. Cartilage becomes brittle and can break apart easily. In some cases this leads to spinal injuries such as prolapsed intervertebral discs. […] Deposits around the trachea (windpipe), larynx (voice box) and bronchi (air passages to the lungs) may cause shortness of breath and difficulty breathing. […] Deposits around the heart and blood vessels can calcify (harden) and lead to atherosclerotic plaques (hard spots in arteries). […] Pigmentation of the sclera of the eye usually occurs early on. This does not affect vision but appears as brown or grey deposits on the surface of the eye. […] Skin colour changes are most apparent on areas exposed to the sun and where sweat glands are found. Areas most affected include the cheeks, forehead, armpits and genital regions. The skin takes on a blue-black speckled discolouration. Sweat produced has been found to stain clothes. Sometimes nails can be affected and turn a distinct brown colour. […] Life expectancy is normal although patients may be at increased risk of heart conditions and may require surgical treatments for spine, hip, knee and shoulder joint problems.

• #46 Alkaptonuria (Black Urine Disease) – Causes, Symptoms, Diagnosis, Treatment and Prognosis

  https://www.medindia.net/health/conditions/alkaptonuria.htm

  Kidney Prostate Stones: Kidney stones can develop in 50% of affected individuals over 64 years of age. Men with alkaptonuria may also develop prostate stones. Passage of these black stones can be extremely painful. […] Ochronotic Arthropathy: There can be chronic joint pain and inflammation (arthritis). When the spine and large joints such as the hips and knees are affected, it is technically termed as ochronotic arthropathy. […] Ankylosis Kyphosis: Intervertebral discs can flatten, calcify and eventually fuse. This can result in ankylosis, (a condition where the affected joints become stiff and immobile). Moreover, kyphosis or hunchback may occur, where there is an excessive convex curvature of the spine. […] Stiffening of Heart Valves: Accumulation of HGA within the aortic or mitral valves can cause thickening of the valves and narrowing (stenosis) of their openings due to calcification. In some cases, calcification of the coronary blood vessels may also occur.

• #47 Alkaptonuria – Wikipedia

  https://en.wikipedia.org/wiki/Alkaptonuria

  Patients with alkaptonuria are asymptomatic as children or young adults, but their urine may turn brown or even inky black if collected and left exposed to open air. […] After the age of 30, people begin to develop pain in the weight-bearing joints of the spine, hips, and knees. The pain can be severe to the point that interferes with activities of daily living and may affect the ability to work. Joint-replacement surgery (hip and shoulder) is often necessary at a relatively young age. […] Valvular heart disease, mainly calcification and regurgitation of the aortic and mitral valves, may occur, and in severe and progressive cases, valve replacement may be necessary. Irregularities in the heart rhythm and heart failure affect a significant proportion of people with alkaptonuria (40% and 10%, respectively).

• #48 Alkaptonuria – Wikipedia

  https://en.wikipedia.org/wiki/Alkaptonuria

  Patients with alkaptonuria are asymptomatic as children or young adults, but their urine may turn brown or even inky black if collected and left exposed to open air. […] After the age of 30, people begin to develop pain in the weight-bearing joints of the spine, hips, and knees. The pain can be severe to the point that interferes with activities of daily living and may affect the ability to work. Joint-replacement surgery (hip and shoulder) is often necessary at a relatively young age. […] Valvular heart disease, mainly calcification and regurgitation of the aortic and mitral valves, may occur, and in severe and progressive cases, valve replacement may be necessary. Irregularities in the heart rhythm and heart failure affect a significant proportion of people with alkaptonuria (40% and 10%, respectively).

• #49 Alkaptonuria – Wikipedia

  https://en.wikipedia.org/wiki/Alkaptonuria

  Patients with alkaptonuria are asymptomatic as children or young adults, but their urine may turn brown or even inky black if collected and left exposed to open air. […] After the age of 30, people begin to develop pain in the weight-bearing joints of the spine, hips, and knees. The pain can be severe to the point that interferes with activities of daily living and may affect the ability to work. Joint-replacement surgery (hip and shoulder) is often necessary at a relatively young age. […] Valvular heart disease, mainly calcification and regurgitation of the aortic and mitral valves, may occur, and in severe and progressive cases, valve replacement may be necessary. Irregularities in the heart rhythm and heart failure affect a significant proportion of people with alkaptonuria (40% and 10%, respectively).

• #50 Alkaptonuria: Causes, Symptoms and Diagnosis

  https://www.healthline.com/health/alkaptonuria

  The World Institutes of Health reports adults can experience a buildup of homogentisic acid in cartilage, resulting in arthritis. As a result those with alkaptonuria may need a shoulder, knee, or hip replacement. […] The life expectancy for people with alkaptonuria is fairly normal. However, the disease puts you at much higher risk of certain disorders, including: arthritis in your spine, hips, shoulders, and knees, tearing of your Achilles tendon, hardening of your hearts aortic and mitral valves, hardening of your coronary arteries, kidney and prostate stones. […] Some of these complications can be delayed with regular checkups. Your doctor will want to monitor you regularly. Tests to monitor the progress of your condition might include: spinal X-rays to check for disk degeneration and calcification in your lumbar spine, chest X-rays to monitor your aortic and mitral heart valves, CT (computed tomography) scans to find signs of coronary artery disease.

• #51 Alkaptonuria – Wikipedia

  https://en.wikipedia.org/wiki/Alkaptonuria

  Patients with alkaptonuria are asymptomatic as children or young adults, but their urine may turn brown or even inky black if collected and left exposed to open air. […] After the age of 30, people begin to develop pain in the weight-bearing joints of the spine, hips, and knees. The pain can be severe to the point that interferes with activities of daily living and may affect the ability to work. Joint-replacement surgery (hip and shoulder) is often necessary at a relatively young age. […] Valvular heart disease, mainly calcification and regurgitation of the aortic and mitral valves, may occur, and in severe and progressive cases, valve replacement may be necessary. Irregularities in the heart rhythm and heart failure affect a significant proportion of people with alkaptonuria (40% and 10%, respectively).

• #52 Alkaptonuria

  https://www.nhs.uk/conditions/alkaptonuria/

  Many people develop brown or black spots on the whites of their eyes. […] Another sign in many adults with alkaptonuria is thickening of ear cartilage. […] Alkaptonuria can result in discoloured sweat, which can stain clothes and cause some people to have blue or black speckled areas of skin. […] If the bones and muscles around the lungs become stiff, it can prevent the chest expanding and lead to shortness of breath or difficulty breathing. […] Deposits of homogentisic acid around heart valves can cause them to narrow, harden and turn brittle and black. […] This can lead to heart disease and may require heart valve replacements. […] Alkaptonuria is a lifelong condition. […] Painkillers and lifestyle changes may help you cope with the symptoms. […] People with alkaptonuria have a normal life expectancy. However, they will eventually experience symptoms, such as pain and loss of movement in the joints and spine, which can affect quality of life.

• #53 Alkaptonuria and ochronosis

  https://dermnetnz.org/topics/alkaptonuria-and-ochronosis

  Bones and cartilage of the lower back, knees, shoulders and hips are most affected. Firstly patients suffer low back pain with stiffness, followed by knee, shoulder and hip pain over the next 10 years. Cartilage becomes brittle and can break apart easily. In some cases this leads to spinal injuries such as prolapsed intervertebral discs. […] Deposits around the trachea (windpipe), larynx (voice box) and bronchi (air passages to the lungs) may cause shortness of breath and difficulty breathing. […] Deposits around the heart and blood vessels can calcify (harden) and lead to atherosclerotic plaques (hard spots in arteries). […] Pigmentation of the sclera of the eye usually occurs early on. This does not affect vision but appears as brown or grey deposits on the surface of the eye. […] Skin colour changes are most apparent on areas exposed to the sun and where sweat glands are found. Areas most affected include the cheeks, forehead, armpits and genital regions. The skin takes on a blue-black speckled discolouration. Sweat produced has been found to stain clothes. Sometimes nails can be affected and turn a distinct brown colour. […] Life expectancy is normal although patients may be at increased risk of heart conditions and may require surgical treatments for spine, hip, knee and shoulder joint problems.

• #54 Alkaptonuria – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/alkaptonuria/

  The disease can manifest in many ways these are often grouped into three major categories, namely ochronosis, homogenistic aciduria, and ochronotic osteoarthropathy. Ochronosis typically becomes evident in a patient’s 30s or 40s and results from a buildup of a specific organic compound in various parts of the body, including the connective tissues. Over time, ochronotic arthropathy, or joint disease, develops due to a buildup of homogentisic acid polymers in the cartilage that cushions the joints. […] Signs and symptoms of Alkaptonuria include: – Darkening of urine when exposed to air for a prolonged time, due to the reaction of homogentisic acid with the air. However, in some cases, the urine may not darken, making this sign unreliable. – Arthritis, particularly affecting the spine, hips, and knees. Nearly everyone with Alkaptonuria will eventually develop arthritis. – Back pain, specifically in the lower and middle back regions, often appearing around age 30. – Spine-related problems as a person grows older, including a forward-leaning posture, narrowing of the spaces within the spine, and pressure on the spinal cord. – Ochronosis, which becomes evident in a patient’s 30s or 40s and results from a buildup of a specific organic compound in various parts of the body, including connective tissues. – Ochronotic arthropathy, or joint disease, develops due to a buildup of homogentisic acid polymers in the cartilage that cushions the joints. – Grey pigmentation in the ear cartilage or the whites of the eyes, or discolored skin. – Lower back pain and joint swelling due to arthritis, limited joint movement, compromised spine and chest mobility, and a greater likelihood of fractures due to decreased bone density. – Decreased lung capacity and restrictive lung disease. – Heart conditions such as narrowing or leaking of the aortic valve, irregular heartbeats, heart failure, and an increased risk of coronary artery disease. – Peripheral neuropathy, ringing in the ears, double vision, and an increased risk of stroke. – Higher incidence of kidney, gallbladder, and prostate stones.

• #55 Alkaptonuria

  https://www.nhs.uk/conditions/alkaptonuria/

  Many people develop brown or black spots on the whites of their eyes. […] Another sign in many adults with alkaptonuria is thickening of ear cartilage. […] Alkaptonuria can result in discoloured sweat, which can stain clothes and cause some people to have blue or black speckled areas of skin. […] If the bones and muscles around the lungs become stiff, it can prevent the chest expanding and lead to shortness of breath or difficulty breathing. […] Deposits of homogentisic acid around heart valves can cause them to narrow, harden and turn brittle and black. […] This can lead to heart disease and may require heart valve replacements. […] Alkaptonuria is a lifelong condition. […] Painkillers and lifestyle changes may help you cope with the symptoms. […] People with alkaptonuria have a normal life expectancy. However, they will eventually experience symptoms, such as pain and loss of movement in the joints and spine, which can affect quality of life.

• #56 Alkaptonuria: Causes, Symptoms and Diagnosis

  https://www.healthline.com/health/alkaptonuria

  Alkaptonuria is a lifelong condition, but there are many ways to help manage your symptoms. […] Symptoms become more obvious as you age. […] Your urine may turn dark brown or black when its exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis. […] For example, you may notice chronic stiffness or pain in your lower back or large joints. […] Other symptoms of alkaptonuria include: dark spots in the sclera (white) of your eyes, thickened and darkened cartilage in your ears, blue speckled discoloration of your skin, particularly around sweat glands, dark-colored sweat or sweat stains, black earwax, kidney stones and prostate stones, arthritis (especially hip and knee joints). […] Alkaptonuria can also lead to heart problems. The buildup of homogentisic acid causes your heart valves to harden. This can keep them from closing properly, resulting in aortic and mitral valve disorders.

• #57 Alkaptonuria: Definition, Causes, Treatments, and More

  https://resources.healthgrades.com/right-care/symptoms-and-conditions/alkaptonuria

  Many people remain unaware of their condition until adulthood. As ochronosis progresses, adults around or over 30 years old may notice discoloration of tissues, including the outer ear cartilage, white areas of the eyes, and skin on the hands. […] If you have alkaptonuria, you may experience stiffness, decreased joint mobility, and then knee, hip, and shoulder pain. Lowered mineral content in your bones may increase your risk of fractures. […] If the bones and muscles around the lungs become stiff, it can become more difficult for your chest to expand efficiently. This may lead to shortness of breath or difficulty breathing. […] Deposits of homogentisic acid around heart valves can lead to heart disease, an irregular heart rate, coronary artery disease, and heart failure. […] Deposits of homogentisic acid can also lead to the formation of kidney, bladder, and prostate stones. Experts state that by 64 years old, 50% of people with alkaptonuria have a history of kidney stones. […] Alkaptonuria is a rare genetic condition that may be unnoticeable until adulthood. Symptoms can include dark urine, discoloration of soft tissues and cartilage, and joint pain and stiffness.

• #58 Alkaptonuria (Black Urine Disease) – Causes, Symptoms, Diagnosis, Treatment and Prognosis

  https://www.medindia.net/health/conditions/alkaptonuria.htm

  Kidney Prostate Stones: Kidney stones can develop in 50% of affected individuals over 64 years of age. Men with alkaptonuria may also develop prostate stones. Passage of these black stones can be extremely painful. […] Ochronotic Arthropathy: There can be chronic joint pain and inflammation (arthritis). When the spine and large joints such as the hips and knees are affected, it is technically termed as ochronotic arthropathy. […] Ankylosis Kyphosis: Intervertebral discs can flatten, calcify and eventually fuse. This can result in ankylosis, (a condition where the affected joints become stiff and immobile). Moreover, kyphosis or hunchback may occur, where there is an excessive convex curvature of the spine. […] Stiffening of Heart Valves: Accumulation of HGA within the aortic or mitral valves can cause thickening of the valves and narrowing (stenosis) of their openings due to calcification. In some cases, calcification of the coronary blood vessels may also occur.

• #59 Alkaptonuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/alkaptonuria/

  The body removes the excess pigment in urine. However, removing the large pigment deposits found in people with alkaptonuria can put strain on the kidneys, and this can lead to kidney (renal) failure. […] With appropriate medical management, people with alkaptonuria generally have a normal life expectancy.

• #60 Alkaptonuria – ThinkGenetic Foundation

  https://thinkgenetic.org/diseases/alkaptonuria/

  Alkaptonuria is progressive. Discolored urine is present at birth. The, ochronosis develops around 30 years of age, and arthritis begins around 50 years of age. […] Discolored urine is present from birth. Ochronosis is present around 30 years of age on average, and arthritis begins around 50 years of age on average.

• #61 A novel deep intronic variant strongly associates with Alkaptonuria | npj Genomic Medicine

  https://www.nature.com/articles/s41525-021-00252-2

  Alkaptonuria is a rare autosomal recessive inherited disorder of tyrosine metabolism, which causes ochronosis, arthropathy, cardiac valvular calcification, and urolithiasis. […] The hallmark of the disease is dark urine, which is caused by the oxidization of HGA. Associated morbidities include ochronosis, ochronotic arthropathy, cardiac valvular calcification, and urolithiasis in the 4th to 6th decades of life. […] Although the life expectancy of patients with AKU is not reduced, their quality of life deteriorates mainly due to painful joint diseases. […] Usually, symptoms of AKU initiate from ochronotic pigmentation in the 4th decade of life, which is followed by painful joint destruction requiring artificial joint replacement and cardiac valvular problems in the mid-50s and the formation of renal stones in the 60s.

• #62 Alkaptonuria – ThinkGenetic Foundation

  https://thinkgenetic.org/diseases/alkaptonuria/

  Alkaptonuria is progressive. Discolored urine is present at birth. The, ochronosis develops around 30 years of age, and arthritis begins around 50 years of age. […] Discolored urine is present from birth. Ochronosis is present around 30 years of age on average, and arthritis begins around 50 years of age on average.

• #63 Alkaptonuria – ThinkGenetic Foundation

  https://thinkgenetic.org/diseases/alkaptonuria/

  Alkaptonuria is progressive. Discolored urine is present at birth. The, ochronosis develops around 30 years of age, and arthritis begins around 50 years of age. […] Discolored urine is present from birth. Ochronosis is present around 30 years of age on average, and arthritis begins around 50 years of age on average.

• #64 Alkaptonuria (Black Urine Disease): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/941530-overview

  Life expectancy is normal; however, associated morbidity can be significant. Early involvement of the intervertebral discs at the thoracic and lumbar levels is very common, occurring in approximately 50% of affected individuals. Typically, significant back pain begins from age 30 years. The large joints (knee, shoulder and hip) are very frequently involved; at least half of all patients undergo joint replacement by the middle of the sixth decade of life. […] Because alkaptonuria is a genetic disorder, the deficiency of the HGO enzyme is present from conception. Clinical symptoms, aside from dark-stained diapers, are generally present only after the third decade of life.

• #65 Alkaptonuria (Black Urine Disease): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/941530-overview

  Life expectancy is normal; however, associated morbidity can be significant. Early involvement of the intervertebral discs at the thoracic and lumbar levels is very common, occurring in approximately 50% of affected individuals. Typically, significant back pain begins from age 30 years. The large joints (knee, shoulder and hip) are very frequently involved; at least half of all patients undergo joint replacement by the middle of the sixth decade of life. […] Because alkaptonuria is a genetic disorder, the deficiency of the HGO enzyme is present from conception. Clinical symptoms, aside from dark-stained diapers, are generally present only after the third decade of life.

• #66 Alkaptonuria: Causes, Symptoms & Treatment Options

  https://sehathub.com/alkaptonuria

  Moreover, heart issues might potentially result from alkaptonuria. […] Grey discoloration may be found in the sclerae or ear cartilage. Calcifications may be palpable in the discolored areas, particularly in the cartilage of the ear. Joint mobility diminishes, as in osteoarthritis. Spontaneous fusion of one or more discs may occur, with consequent diminished spinal flexion. Joint effusions, particularly in the knee, are common, and the range of motion may be significantly diminished. […] Life expectancy is normal; however, associated morbidity can be significant. Early involvement of the intervertebral discs at the thoracic and lumbar levels is very common. Typically, significant back pain begins at the age of 30 years. It frequently involves the large joints (knee, shoulder, and hip); at least half of all patients undergo joint replacement by the middle of the sixth decade of life.

• #67 Alkaptonuria (Black Urine Disease): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/941530-overview

  Life expectancy is normal; however, associated morbidity can be significant. Early involvement of the intervertebral discs at the thoracic and lumbar levels is very common, occurring in approximately 50% of affected individuals. Typically, significant back pain begins from age 30 years. The large joints (knee, shoulder and hip) are very frequently involved; at least half of all patients undergo joint replacement by the middle of the sixth decade of life. […] Because alkaptonuria is a genetic disorder, the deficiency of the HGO enzyme is present from conception. Clinical symptoms, aside from dark-stained diapers, are generally present only after the third decade of life.

• #68 Alkaptonuria: Causes, Symptoms & Treatment Options

  https://sehathub.com/alkaptonuria

  Moreover, heart issues might potentially result from alkaptonuria. […] Grey discoloration may be found in the sclerae or ear cartilage. Calcifications may be palpable in the discolored areas, particularly in the cartilage of the ear. Joint mobility diminishes, as in osteoarthritis. Spontaneous fusion of one or more discs may occur, with consequent diminished spinal flexion. Joint effusions, particularly in the knee, are common, and the range of motion may be significantly diminished. […] Life expectancy is normal; however, associated morbidity can be significant. Early involvement of the intervertebral discs at the thoracic and lumbar levels is very common. Typically, significant back pain begins at the age of 30 years. It frequently involves the large joints (knee, shoulder, and hip); at least half of all patients undergo joint replacement by the middle of the sixth decade of life.

• #69

  https://ijneronline.com/HTML_Papers/International%20Journal%20of%20Nursing%20Education%20and%20Research__PID__2021-9-3-26.html

  Alkaptonuria (AKU) is a rare disorder of autosomal recessive inheritance. Characteristically, the excess HGA means sufferers pass dark urine, which upon standing turns black. This is a feature present from birth. Over time patients develop other manifestations of AKU, due to deposition of HGA in collagenous tissue namely ochronosis and ochronotic osteoarthropathy. Although this condition does not reduce life expectancy, it significantly affects quality of life. […] Symptoms become more obvious as you age. Your urine may turn dark brown or black when it’s exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis. For example, you may notice chronic stiffness or pain in your lower back or large joints. Other symptoms of alkaptonuria include: Dark spots in the sclera (white) of your eyes, Thickened and darkened cartilage in your ears, Blue speckled discoloration of your skin, particularly around sweat glands, Dark-colored sweat or sweat stains, Black earwax, Kidney stones and prostate stones, Arthritis (especially hip and knee joints). Alkaptonuria can also lead to heart problems. […] The typical age at requiring joint replacement surgery is 50-55 years.

• #70 Alkaptonuria (Black Urine Disease): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/941530-overview

  Life expectancy is normal; however, associated morbidity can be significant. Early involvement of the intervertebral discs at the thoracic and lumbar levels is very common, occurring in approximately 50% of affected individuals. Typically, significant back pain begins from age 30 years. The large joints (knee, shoulder and hip) are very frequently involved; at least half of all patients undergo joint replacement by the middle of the sixth decade of life. […] Because alkaptonuria is a genetic disorder, the deficiency of the HGO enzyme is present from conception. Clinical symptoms, aside from dark-stained diapers, are generally present only after the third decade of life.

• #71 A novel deep intronic variant strongly associates with Alkaptonuria | npj Genomic Medicine

  https://www.nature.com/articles/s41525-021-00252-2

  Alkaptonuria is a rare autosomal recessive inherited disorder of tyrosine metabolism, which causes ochronosis, arthropathy, cardiac valvular calcification, and urolithiasis. […] The hallmark of the disease is dark urine, which is caused by the oxidization of HGA. Associated morbidities include ochronosis, ochronotic arthropathy, cardiac valvular calcification, and urolithiasis in the 4th to 6th decades of life. […] Although the life expectancy of patients with AKU is not reduced, their quality of life deteriorates mainly due to painful joint diseases. […] Usually, symptoms of AKU initiate from ochronotic pigmentation in the 4th decade of life, which is followed by painful joint destruction requiring artificial joint replacement and cardiac valvular problems in the mid-50s and the formation of renal stones in the 60s.

• #72 What is alkaptonuria? The rare disease that turns your pee black | Live Science

  https://www.livescience.com/health/viruses-infections-disease/what-is-alkaptonuria-the-rare-disease-that-turns-your-pee-black

  One of the earliest signs that someone has alkaptonuria is dark stains in their diapers as babies, because the homogentisic acid in their urine turns black upon exposure to air. […] Besides dark urine, people with alkaptonuria often have no other noticeable symptoms of the disease until they are in their late 20s or early 30s. […] Over time, homogentisic acid continues to build up in a person’s tissues, staining those tissues a slate blue or black color and eventually weakening and damaging them. This can lead to severe deformities in the joints and spine, as well as organ dysfunction, including issues with the kidneys and heart. Symptoms of alkaptonuria tend to be more severe and come on sooner in males than in females. […] Although patients with alkaptonuria tend to have a normal life expectancy, the disease can markedly impact their quality of life. […] There is currently no cure for alkaptonuria, but scientists are studying the potential use of a drug called nitisinone to slow the progression of the disease.

• #73 Alkaptonuria | Contact

  https://contact.org.uk/conditions/alkaptonuria/

  The build-up of HGA leads to premature progressive degeneration in the joints. Chronic joint pain is one of the first symptoms of AKU. Arthritis of the spine, knees and hips causes symptoms of stiffness, pain, swelling and limited motion. Males tend to have an earlier onset of arthritic symptoms with a greater degree of severity than females. Deposits of pigment may cause cartilage to become brittle and eventually to fragment.

• #74 Alkaptonuria

  https://www.nhs.uk/conditions/alkaptonuria/

  Many people develop brown or black spots on the whites of their eyes. […] Another sign in many adults with alkaptonuria is thickening of ear cartilage. […] Alkaptonuria can result in discoloured sweat, which can stain clothes and cause some people to have blue or black speckled areas of skin. […] If the bones and muscles around the lungs become stiff, it can prevent the chest expanding and lead to shortness of breath or difficulty breathing. […] Deposits of homogentisic acid around heart valves can cause them to narrow, harden and turn brittle and black. […] This can lead to heart disease and may require heart valve replacements. […] Alkaptonuria is a lifelong condition. […] Painkillers and lifestyle changes may help you cope with the symptoms. […] People with alkaptonuria have a normal life expectancy. However, they will eventually experience symptoms, such as pain and loss of movement in the joints and spine, which can affect quality of life.

• #75 Alkaptonuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/alkaptonuria/

  The body removes the excess pigment in urine. However, removing the large pigment deposits found in people with alkaptonuria can put strain on the kidneys, and this can lead to kidney (renal) failure. […] With appropriate medical management, people with alkaptonuria generally have a normal life expectancy.

• #76 Alkaptonuria – Wikipedia

  https://en.wikipedia.org/wiki/Alkaptonuria

  Hearing loss affects 40% of people. Also, a propensity to developing kidney stones exists, and eventually also gallstones and stones in the prostate and salivary glands (sialolithiasis) can occur. […] The main impact is on quality of life; many people with alkaptonuria have disabling symptoms such as pain, poor sleep, and breathing symptoms. These generally start in the fourth decade. The typical age at requiring joint replacement surgery is 50-55 years.

• #77 Alkaptonuria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560571/

  Ochronosis commonly presents in the third or fourth decade, which develops as the deposition of benzoquinone acetate in both extra- and intra-cellularly connective tissue. Finally, ochronotic arthropathy develops as an accumulation of Homogentisinic acid polymer within hyaline articular cartilage. […] The pathological effects of ochronosis include arthritis, increased incidence of renal, prostatic, gall bladder stones, ruptures of muscle, tendons, and ligaments. […] This disorder does not seem to affect life expectancy. However, the significant impact is on the patient’s quality of life; for example, lots of people with AKU have experienced symptoms such as lack of sleep, pain, and difficulty breathing. These features begin in the fourth decade.

• #78 Alkaptonuria (Black Urine Disease) – Causes, Symptoms, Diagnosis, Treatment and Prognosis

  https://www.medindia.net/health/conditions/alkaptonuria.htm

  The disease is progressive in nature. There is usually a slow but progressive functional decline in the patient. Complications such as arthritis in the spine, hips, shoulders and knees can develop. There is a greater propensity for the Achilles tendon to rupture and for kidney and prostate stones to develop. The aortic and mitral valves as well as the coronary arteries may become stiff and hardened. The patients experience increased pain and loss of mobility as time progresses, often requiring the use of physical mobility aids such as crutches or wheelchairs. Although cardiac complications may worsen the prognosis, life expectancy is not significantly reduced.

• #79 Alkaptonuria | Health Information from Oak Tree Pharmacy

  https://oaktreepharmacy.co.uk/nhs_conditions_alkaptonuria

  Deposits of homogentisic acid around heart valves can cause them to narrow, harden and turn brittle and black. […] This can lead to heart disease and may require heart valve replacements. […] The deposits can also lead to kidney stones, bladder stones and prostate stones. […] Alkaptonuria is a lifelong condition. […] Painkillers and lifestyle changes may help you cope with the symptoms. […] People with alkaptonuria have a normal life expectancy. However, they will eventually experience symptoms, such as pain and loss of movement in the joints and spine, which can affect quality of life. […] Working and carrying out strenuous physical activity will usually become very difficult, and eventually you may need mobility aids such as a wheelchair to get around.

• #80 Alkaptonuria (Black Urine Disease) – Causes, Symptoms, Diagnosis, Treatment and Prognosis

  https://www.medindia.net/health/conditions/alkaptonuria.htm

  The disease is progressive in nature. There is usually a slow but progressive functional decline in the patient. Complications such as arthritis in the spine, hips, shoulders and knees can develop. There is a greater propensity for the Achilles tendon to rupture and for kidney and prostate stones to develop. The aortic and mitral valves as well as the coronary arteries may become stiff and hardened. The patients experience increased pain and loss of mobility as time progresses, often requiring the use of physical mobility aids such as crutches or wheelchairs. Although cardiac complications may worsen the prognosis, life expectancy is not significantly reduced.

• #81 Orphanet: Alkaptonuria

  https://www.orpha.net/en/disease/detail/56

  Treatment is palliative. Dietary restriction (low protein diet) is beneficial, but compliance is often limited. Medical therapy (paracetamol, non-steroidal anti-inflammatory drugs) associated with physiotherapy help to minimize pain and improve the range of joint motion. Older individuals may require removal and fusion of lumbar discs. Hip or knee joint replacement may be necessary. Therapeutic strategies aimed at perturbing the altered phenylalanine-tyrosine pathway have been devised (e.g. nitisinone). Off-label usage of nitisinone has been shown to slow the rate of disease progression; however, the long-term effectiveness and safety in adult patients with alkaptonuria, as well as the most suitable age for intervention, remains to be evaluated (currently an open-label clinical trial and observation study are under way). […] Life expectancy is not significantly reduced but pain can be constant and progressive functional decline is observed with a loss of mobility; patients often require the use of physical aids (crutches, wheelchair). Cardiac complications are often life-threatening and may worsen the prognosis.

• #82 Alkaptonuria symptoms, treatments & forums | PatientsLikeMe

  https://www.patientslikeme.com/conditions/alkaptonuria

  Alkaptonuria is a rare autosomal recessive disorder caused by homogentisic acid oxidase deficiency, a substance that is part of tyrosine metabolism. Homogentisic acid oxidation products accumulate in and darken skin, and crystals precipitate in joints. Urine exposed to air takes on a dark color. […] Common symptom Pain […] 23 alkaptonuria patients report severe pain (29%) […] 33 alkaptonuria patients report moderate pain (41%) […] 13 alkaptonuria patients report mild pain (16%) […] 10 alkaptonuria patients report no pain (12%) […] Common symptom Fatigue […] 15 alkaptonuria patients report severe fatigue (19%) […] 26 alkaptonuria patients report moderate fatigue (33%) […] 22 alkaptonuria patients report mild fatigue (28%) […] 14 alkaptonuria patients report no fatigue (18%)

• #83 Alkaptonuria symptoms, treatments & forums | PatientsLikeMe

  https://www.patientslikeme.com/conditions/alkaptonuria

  Common symptom Stress […] 3 alkaptonuria patients report severe stress (13%) […] 8 alkaptonuria patients report moderate stress (36%) […] 7 alkaptonuria patients report mild stress (31%) […] 4 alkaptonuria patients report no stress (18%) […] Common symptom Anxious mood […] 5 alkaptonuria patients report severe anxious mood (6%) […] 17 alkaptonuria patients report moderate anxious mood (22%) […] 22 alkaptonuria patients report mild anxious mood (28%) […] 33 alkaptonuria patients report no anxious mood (42%) […] Common symptom Depressed mood […] 4 alkaptonuria patients report severe depressed mood (5%) […] 15 alkaptonuria patients report moderate depressed mood (19%) […] 27 alkaptonuria patients report mild depressed mood (35%) […] 31 alkaptonuria patients report no depressed mood (40%).

• #84 A novel deep intronic variant strongly associates with Alkaptonuria | npj Genomic Medicine

  https://www.nature.com/articles/s41525-021-00252-2

  However, some of our three patients as young as 12 years already had ochronosis or arthralgia. […] The suspicious ochronosis and arthralgia in a portion of them alert us to the potential for more serious symptoms in the future. […] Alkaptonuria is rare in Taiwan and East Asia, with HGD variants being mostly novel. More efforts involving molecular analysis are expected to contribute to the diagnosis of new cases in this region.

• #85 Does Your Patient’s Urine Turns Dark? Alkaptonuria and Low Back Ache: A Literature Review | Journal of Orthopaedic Case Reports

  https://jocr.co.in/wp/2014/10/14/2250-0685-220-fulltext/

  Low back ache as the primary presentation of alkaptonuria. […] Though low back is a common symptom of alkaptonuria but, in the absence of ochronosis it is rare. […] A 38-year-old male, embroidery worker presented with chronic low back ache with history of staining of clothes in infancy. […] Though alkaptonuria is a very rare disease, and the occurrence of low back-ache in absence of ochronosis is much rarer. […] The common most symptoms of joint and connective tissue involvement among alkaptonurics is back stiffness, low back pain and sciatica rarely. […] Our patient too had presented with chronic low back pain without any neurological involvement. […] Alkaptonuria is a rare disease whose incidence is approximately 1:1 million individuals. […] Early diagnosis and high index of suspicion are advantageous as symptomatic treatment of the alkaptonuria can be initiated, and evaluation of other systemic organs can be done in early stages itself.

• #86 Possible Relationship Between Infertility and Alkaptonuria – Electronic Journal of General Medicine

  https://www.ejgm.co.uk/article/possible-relationship-between-infertility-and-alkaptonuria-6826

  Alkaptonuria is a rare metabolic disease which is not known to cause infertility up to now. Reported manifestations are mainly darkening of urine, ochronotic pigmentation of skin and various musculoskeletal symptoms. […] After diagnosis of alkaptonuria, noticed them to have infertility. […] After detailed investigation we noticed coexistence of infertility and alkaptonuria in three of eight couples.

• #87 Alkaptonuria / Metabolic Diseases / Types of brain injury – brain disorders | Braininjury-explanation.com

  https://www.braininjury-explanation.com/types-of-brain-injury-brain-disorders/metabolic-diseases/alkaptonuria

  Alkaptonuria (AKU) is a rare metabolic disorder caused by a genetic abnormality that results in a deficiency of the enzyme homogentisate dioxygenase. Usually, this condition does not cause symptoms until adulthood. […] Symptoms may include: dark, almost black discoloration of the urine when exposed to air, and cartilage damage with severe joint pain/arthritis symptoms. AKU patients can also experience kidney stones and kidney problems. The buildup of the enzyme HGA can harden and damage the blood vessels and heart valves, which can lead to a heart complication such as heart failure. […] As the patient ages, black spots may appear in the whites of the eyes. Some people develop a bluish to blue-black discoloration of the ears. The areas of the skin exposed to the sun and where sweat glands are located may develop a blue-black mottled discoloration. In rare cases, the buildup of homogentisic acid can also affect the brain. This can lead to neurological complications. Symptoms such as memory problems, cognitive decline or motor disorders. A possible link between AKU and Parkinson’s disease has been identified. A study has determined that Parkinson’s disease occurs approximately 20 times more often in people with Alkaptonuria than in people who do not suffer from Alkaptonuria.

• #88 Alkaptonuria / Metabolic Diseases / Types of brain injury – brain disorders | Braininjury-explanation.com

  https://www.braininjury-explanation.com/types-of-brain-injury-brain-disorders/metabolic-diseases/alkaptonuria

  Alkaptonuria (AKU) is a rare metabolic disorder caused by a genetic abnormality that results in a deficiency of the enzyme homogentisate dioxygenase. Usually, this condition does not cause symptoms until adulthood. […] Symptoms may include: dark, almost black discoloration of the urine when exposed to air, and cartilage damage with severe joint pain/arthritis symptoms. AKU patients can also experience kidney stones and kidney problems. The buildup of the enzyme HGA can harden and damage the blood vessels and heart valves, which can lead to a heart complication such as heart failure. […] As the patient ages, black spots may appear in the whites of the eyes. Some people develop a bluish to blue-black discoloration of the ears. The areas of the skin exposed to the sun and where sweat glands are located may develop a blue-black mottled discoloration. In rare cases, the buildup of homogentisic acid can also affect the brain. This can lead to neurological complications. Symptoms such as memory problems, cognitive decline or motor disorders. A possible link between AKU and Parkinson’s disease has been identified. A study has determined that Parkinson’s disease occurs approximately 20 times more often in people with Alkaptonuria than in people who do not suffer from Alkaptonuria.

• #89 Alkaptonuria: Causes, Symptoms and Diagnosis

  https://www.healthline.com/health/alkaptonuria

  The World Institutes of Health reports adults can experience a buildup of homogentisic acid in cartilage, resulting in arthritis. As a result those with alkaptonuria may need a shoulder, knee, or hip replacement. […] The life expectancy for people with alkaptonuria is fairly normal. However, the disease puts you at much higher risk of certain disorders, including: arthritis in your spine, hips, shoulders, and knees, tearing of your Achilles tendon, hardening of your hearts aortic and mitral valves, hardening of your coronary arteries, kidney and prostate stones. […] Some of these complications can be delayed with regular checkups. Your doctor will want to monitor you regularly. Tests to monitor the progress of your condition might include: spinal X-rays to check for disk degeneration and calcification in your lumbar spine, chest X-rays to monitor your aortic and mitral heart valves, CT (computed tomography) scans to find signs of coronary artery disease.

• #90 Alkaptonuria: Symptoms, Causes, Treatment

  https://www.medicoverhospitals.in/diseases/alkaptonuria/

  While some symptoms of alkaptonuria are noticeable early in life, others may not become apparent until adulthood. The accumulation of homogentisic acid can lead to various complications over time. […] The most recognizable early symptom, noticeable in infancy, is dark urine. […] Darkening of urine when exposed to air is one of the hallmark symptoms of alkaptonuria. […] Symptoms include darkening of urine, arthritis, and bluish pigmentation in ear cartilage and other tissues. […] The buildup of homogentisic acid can cause severe joint damage, leading to chronic pain and mobility issues. […] Routine check-ups with healthcare providers are essential to monitor the progression of the disease and adjust treatment plans as needed. Regular imaging studies can help assess joint health and detect early signs of cardiovascular complications.

• #91 Alkaptonuria: Symptoms, Causes, Treatment

  https://www.medicoverhospitals.in/diseases/alkaptonuria/

  While some symptoms of alkaptonuria are noticeable early in life, others may not become apparent until adulthood. The accumulation of homogentisic acid can lead to various complications over time. […] The most recognizable early symptom, noticeable in infancy, is dark urine. […] Darkening of urine when exposed to air is one of the hallmark symptoms of alkaptonuria. […] Symptoms include darkening of urine, arthritis, and bluish pigmentation in ear cartilage and other tissues. […] The buildup of homogentisic acid can cause severe joint damage, leading to chronic pain and mobility issues. […] Routine check-ups with healthcare providers are essential to monitor the progression of the disease and adjust treatment plans as needed. Regular imaging studies can help assess joint health and detect early signs of cardiovascular complications.

• #92 Does Your Patient’s Urine Turns Dark? Alkaptonuria and Low Back Ache: A Literature Review | Journal of Orthopaedic Case Reports

  https://jocr.co.in/wp/2014/10/14/2250-0685-220-fulltext/

  Low back ache as the primary presentation of alkaptonuria. […] Though low back is a common symptom of alkaptonuria but, in the absence of ochronosis it is rare. […] A 38-year-old male, embroidery worker presented with chronic low back ache with history of staining of clothes in infancy. […] Though alkaptonuria is a very rare disease, and the occurrence of low back-ache in absence of ochronosis is much rarer. […] The common most symptoms of joint and connective tissue involvement among alkaptonurics is back stiffness, low back pain and sciatica rarely. […] Our patient too had presented with chronic low back pain without any neurological involvement. […] Alkaptonuria is a rare disease whose incidence is approximately 1:1 million individuals. […] Early diagnosis and high index of suspicion are advantageous as symptomatic treatment of the alkaptonuria can be initiated, and evaluation of other systemic organs can be done in early stages itself.

• #93 Alkaptonuria: Causes, Symptoms, Diagnosis, and Treatment Options Explained | OnlyMyHealth

  https://www.onlymyhealth.com/alkaptonuria-causes-symptoms-diagnosis-treatment-12977827239

  Dark, or black, urine is a classic sign of alkaptonuria, which occurs when the urine is exposed to air. […] Additionally, patients may notice joint pain or stiffness, particularly in the spine and large joints, and the development of dark pigmentation in connective tissues, known as ochronosis, which can affect the skin, ears, and eyes. […] Over the years, patients may also develop heart problems, as the heart valves can become calcified and stiff, leading to cardiovascular issues, the doctor added. […] Alkaptonuria is a lifelong condition that requires careful management to prevent complications and maintain quality of life. Early diagnosis and appropriate interventions, such as medication, lifestyle modifications, and regular medical check-ups, can help individuals manage the symptoms effectively.

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