Materiały źródłowe

• #1 Homocystinuria Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/homocystinuria

  Homocystinuria is a genetic disorder that affects the metabolism of the amino acid methionine. […] Tests that may be ordered include any of the following: […] Genetic testing […] Homocysteine level […] If the diagnosis is made in childhood, starting a low-methionine diet quickly may prevent some intellectual disability and other complications of the disease. […] Genetic counseling is recommended for people with a family history of homocystinuria who want to have children. Prenatal diagnosis of homocystinuria is available. This involves culturing amniotic cells or chorionic villi to test for cystathionine synthase (the enzyme that is missing in homocystinuria).

• #1 Homocystinuria

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

  At around 5 days old, babies are offered a newborn blood spot test to check if they have HCU. This involves pricking your baby’s heel to collect drops of blood to test. […] If HCU is diagnosed, treatment can be given to reduce the risk of serious complications. Treatment may include trial doses of vitamin B6 (pyridoxine), a special diet and advice. […] With early diagnosis and the correct treatment, the majority of children with HCU are able to live healthy lives. However, treatment for HCU must be continued for life. […] Regular blood tests will also be needed to monitor the amount of homocysteine in their blood. […] Medicine for HCU needs to be taken regularly, as directed by your doctor.

• #1 Homocystinuria (HCY)

  https://www.wadsworth.org/node/2592/printable/print

  New York State Method of Screening (First Tier): Screening for homocystinuria is accomplished by measuring methionine by tandem mass spectrometry (MS/MS). […] Diagnostic testing may include plasma homocysteine, plasma amino acids, urine homocysteine and CBS gene testing.

• #1 Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1524/

  Homocystinuria caused by cystathionine -synthase (CBS) deficiency is characterized by involvement of the eye (ectopia lentis and/or severe myopia), skeletal system (excessive height, long limbs, scoliosis, and pectus excavatum), vascular system (thromboembolism), and CNS (developmental delay/intellectual disability). […] The cardinal biochemical features of homocystinuria include markedly increased concentrations of plasma total homocysteine and methionine. The diagnosis can be substantiated by detection of biallelic pathogenic variants in CBS, the gene encoding cystathionine -synthase. […] Guidelines for the diagnosis and management of classic homocystinuria have been developed in Europe. These European guidelines recommend total homocysteine (tHcy) accompanied by plasma amino acid analysis as the frontline tests for diagnosis; tHcy above 100 umol/L but occasionally lower (normal: 15 umol/L), when accompanied by high or borderline high methionine, makes the diagnosis very likely. For classic homocystinuria diagnosis, it is imperative that both the total plasma homocysteine concentration and the methionine concentration (as determined by plasma amino acid analysis) be obtained.

• #1 Homocystinuria: Vitamin Deficiency Signs in Children

  https://www.verywellhealth.com/homocystinuria-7553029

  A blood test is necessary to diagnose homocystinuria. Newborns receive the newborn screening after birth, which tests for homocystinuria, among other conditions. […] The blood test measures how much methionine and homocysteine are in the blood. An out-of-range test result does not diagnose homocystinuria. The healthcare provider will follow up with additional blood tests and genetic testing to confirm a diagnosis. […] A false-positive result, in which the test inaccurately indicates the condition, is rare but can happen if the infant was born prematurely or received liquid nutrition intravenously, such as with total perenteral nutrition (TPN). A false-negative result, indicating the condition is present when it is not, can occur if the test is given before the baby is 24 hours old.

• #1 Meet the flok: Classical Homocystinuria

  https://flok.org/news/meet-the-flok-hcu

  The focus of Danaes current advocacy work is early detection and diagnosis of Homocystinuria. She notes that approximately 50% of Homocystinuria cases are missed because the newborn screening tests are not sensitive enough. […] The biomarker methionine is used to screen for the condition, but those with the condition have a low value of methionine in their blood at birth. Many state newborn screens use a methionine cutoff level too high to effectively detect positive cases. (Homocysteine is the primary diagnostic marker for Homocystinuria, but its testing process is more complex, and no states currently use it). HCU Network America advocates for legislation to lower state cutoff levels and ensure every baby born with the condition receives a diagnosis within those early days of life; prompt treatment is crucial to reduce adverse health outcomes. […] Danae encourages individuals with Homocystinuria and their families to contact their state newborn screening laboratories to promote improved processes The goal is timely and accessible treatment for everyone born with this condition.

• #1 Homocystinuria: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001199.htm

  Homocystinuria is a genetic disorder that affects the metabolism of the amino acid methionine. […] Symptoms may occur as mildly delayed development or failure to thrive. Increasing visual problems may lead to diagnosis of this condition. […] The health care provider may notice that the child is tall and thin. […] Tests that may be ordered include any of the following: Amino acid screen of blood and urine, Genetic testing, Homocysteine level, Liver biopsy and enzyme assay, Skeletal x-ray, Skin biopsy with a fibroblast culture, Standard ophthalmic exam. […] If the diagnosis is made in childhood, starting a low-methionine diet quickly may prevent some intellectual disability and other complications of the disease. […] Contact your provider if you or a family member shows symptoms of this disorder, especially if you have a family history of homocystinuria. […] Prenatal diagnosis of homocystinuria is available. This involves culturing amniotic cells or chorionic villi to test for cystathionine synthase (the enzyme that is missing in homocystinuria).

• #1 Newborn screening information for homocystinuria | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/homocystinuria

  Your babys doctor may ask you if your baby is showing any of the signs of HCY (see Early Signs below). If your baby has certain signs, your babys doctor may suggest starting immediate treatment. […] If your babys newborn screening result for homocystinuria (HCY) was out of the normal range, your babys doctor or the state screening program will contact you to arrange for your baby to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. […] Follow-up testing will involve checking your babys urine and blood samples for harmful levels of acids and toxins. Certain acids and toxins build up in the body when a child has an amino acid condition, so measuring the levels of these substances in your babys body can help doctors determine if your baby has a condition. A high amount of certain amino acids (homocysteine and methionine) in the blood and a high amount of homocysteine in the urine might indicate that your baby has HCY.

• #1 Homocystinuria diagnosis and management: it is not all classical | Journal of Clinical Pathology

  https://jcp.bmj.com/content/75/11/744

  Homocystinuria (HCU) refers to a group of inherited disorders of homocysteine metabolism associated with high blood homocysteine concentration, thromboembolic tendency and neurocognitive symptoms. […] The correct diagnosis can be inferred from additional laboratory investigations including a complete blood count and quantitation of methionine and methylmalonic acid. […] Lowering homocysteine reverses thromboembolic risk. […] To aid interpretation of an abnormal tHCy result, samples for tHCy should be accompanied by contemporaneous samples for complete blood count (CBC) to include haemoglobin (Hb) and mean cell volume (MCV), and for vitamin B12, folate and renal function. […] Once secondary causes are excluded, measurement of other amino acids in the HCy metabolic pathway, notably methionine and cystine, with quantitation of MMA in plasma or urine helps to distinguish between the genetic conditions of classical HCU and remethylation defects caused by MTHF reductase (MTHFR) or a disorder of cobalamin metabolism.

• #1 Homocystinuria (HCU): Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/25160-homocystinuria

  How is homocystinuria diagnosed? In the United States, the newborn screening test checks for metabolic conditions, including homocystinuria. The homocysteine test measures the levels of homocysteine and methionine in your babys blood. If the test result is positive, your babys healthcare provider will request additional tests to confirm the result. […] If you develop symptoms of homocystinuria, your healthcare provider will order a homocysteine test to confirm the condition. If the results show you have classical homocystinuria, your provider will request another test to determine which subtype you have. This test is called the vitamin B6 challenge. The test determines how youll respond to vitamin B6 supplementation so your provider can develop the right treatment plan for you. […] Genetic testing can look for mutations in the genes that cause homocystinuria. But healthcare providers dont typically use them because the condition can usually be diagnosed based on the homocysteine test alone.

• #1 Homocystinuria diagnosis and management: it is not all classical | Journal of Clinical Pathology

  https://jcp.bmj.com/content/75/11/744

  Testing for pyridoxine responsiveness forms an essential part of the diagnostic process for any patient newly diagnosed with HCU. […] In fully pyridoxine-responsive HCU, target tHCy can be attained with oral pyridoxine alone (table 2) typically with doses in excess of the recommended daily allowance, ranging from 300 to 900mg/day in adults and 10mg/kg/day to a maximum of 500mg/day in children. […] In non-pyridoxine-responsive HCU and some partially responsive patients, target tHCy can only be attained by additionally following a protein restricted diet to limit intake of the essential amino acid, methionine, the precursor to HCy production in the transsulphuration pathway. […] In all forms of HCU, routine supplementation with folate and vitamin B12 is advisable as a low risk non-evidence-based intervention to prevent nutritional deficiencies of these vitamins contributing to treatment resistance.

• #1 Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1524/

  The diagnosis of classic homocystinuria is established in a proband by measurement of plasma total homocysteine (tHcy) and amino acids in plasma and/or by identification of biallelic pathogenic variants in CBS through molecular genetic testing. Enzyme analysis of cystathionine -synthase (CBS) activity may be performed if pathogenic variants are not identified. […] Molecular genetic testing approaches can include single-gene testing or use of a multigene panel.

• #1 Homocystinuria: MedlinePlus GeneticsLock

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

  Homocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins (amino acids) properly. […] The signs and symptoms of homocystinuria typically develop during childhood, although some mildly affected people may not show signs and symptoms until adulthood. […] Variants (also called mutations) in the CBS, MTHFR, MTR, MTRR, and MMADHC genes cause homocystinuria. […] Variants in the CBS gene cause classic homocystinuria. […] This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. […] Although people who carry one altered copy and one normal copy of the CBS gene do not have homocystinuria, they are more likely than people without a CBS variant to have shortages (deficiencies) of vitamin B12 and folic acid. […] Genetic Testing Registry: Classic homocystinuria […] Genetic Testing Registry: Homocystinuria […] Newborn screening for homocystinuria.

• #1 Homocystinuria: Causes, Symptoms, and Treatment Options

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

  The diagnosis of homocystinuria is a component of newborn screening programs in several nations, including India. By guaranteeing prompt treatment, early detection through these screens can significantly enhance results. […] The diagnosis of homocystinuria is usually done through biochemical tests that check the levels of homocysteine, methionine, and other metabolites in the blood and urine. If these levels are high, it indicates homocystinuria. […] Genetic testing helps confirm homocystinuria diagnosis by identifying mutations in the CBS gene or related genes. It is also useful for screening carriers and diagnosing the condition before birth. […] In some cases, homocystinuria radiology can be useful in identifying bone-related issues such as osteoporosis or deformities, which are common in affected individuals. Imaging tests like X-rays and MRIs help assess complications linked to the condition. […] Advances in genetic testing and biochemical assays are improving the accuracy and speed of homocystinuria diagnosis. Early and accurate diagnosis is crucial for initiating timely treatment and preventing complications.

• #1 Newborn screening information for homocystinuria | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/homocystinuria

  With early and on-going treatment, children with homocystinuria (HCY) can have healthy growth and development. Treatment can reduce the chances for developing blood clots, vision trouble, heart disease, and strokes. This is why it is important to have newborn screening for HCY. […] Because HCY is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for HCY, and understand what this diagnosis means for other family members and future pregnancies.

• #1 Homocystinuria/Homocysteinemia: Overview, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1115062-workup

  Several studies have pointed out that early diagnosis and institution of treatment and dietary restriction is likely to slow the progression of disease in homocystinuria as well as to reverse some of the features. If family history and sibling history suggest homocystinuria, screening tests should be advised. […] If homocystinuria is suspected on the basis of history, physical examination, and family history, the patient may be transferred to a tertiary care center, where expertise in a variety of relevant fields is more likely to be available. […] The urine screening test for sulfur-containing amino acids, called the cyanide nitroprusside test, can be undertaken; however, high rates of false-negative as well as false-positive results are reported. […] Measurement of CBS activity in cultured fibroblasts provides definitive support for the diagnosis.

• #1

  https://omim.org/entry/236200

  Some patients have been reported to have a milder form of homocystinuria, which is characterized by increased plasma homocysteine and increased risk for thrombotic events in young adulthood, but without the other skeletal, ocular, or nervous system manifestations observed in classic homocystinuria. […] Spaeth and Barber (1967) described a silver-nitroprusside test that was almost completely specific for homocystine. […] Wadman et al. (1983) referred to the cyanide-nitroprusside reaction used in the detection of cystinuria and homocystinuria as the Brand reaction. […] Uhlendorf and Mudd (1968) found that cultured fibroblasts derived from normal skin, as well as cells in amniotic fluid, have cystathionine synthase activity, although the enzyme is not detectable in intact normal skin. Fibroblasts grown from the skin of homocystinuric persons are deficient in the enzyme.

• #1 Diagnosis and Management | Homocystinuria | Balance Metanutrition

  https://pristinemetanutrition.com/diagnosis-management-homocystinuria/

  Homocystinuria is an autosomal recessive condition caused by a deficiency of the enzyme cystathionine–synthase (CBS), which leads to the deficiency of cystathionine and cysteine and the accumulation of homocysteine and methionine. […] The diagnosis of homocystinuria is based on the recognition of the clinical phenotype in conjunction with the identification of an elevated total plasma homocysteine and elevated plasma methionine concentrations (via quantitative plasma amino acid analysis). Low cystine and low cystathionine are also seen. In addition, increased urinary excretion of homocysteine as well as cysteine-homocysteine disulfide can be identified on urine amino acid analysis. Confirmation of the diagnosis can be done via enzyme assay, typically performed on cultured skin fibroblasts, lymphocytes, liver tissue or via molecular studies.

• #1 Homocystinuria diagnosis and management: it is not all classical | Journal of Clinical Pathology

  https://jcp.bmj.com/content/75/11/744

  Until recently, a clinical and biochemical diagnosis would have been confirmed by measurement of fibroblast enzyme activity or complementation analysis. However, rapid advancements in genetics have meant that fibroblast studies have been largely superseded by mutation analysis. […] Prospective or very early initiation of treatment of classical (non-pyridoxine-responsive) HCU before complications arise dramatically improves the outlook for patients and formed the rationale for its inclusion in newborn bloodspot screening programmes in many countries worldwide. […] HCy measurement is indicated as part of the routine evaluation of a child presenting with developmental delay or with neurological features including movement disorder, seizures and myelopathy. […] HCU treatment is summarised in table 2. The primary goal is to maintain plasma tHCy concentration at less than 100 mol/L in adults and less than 50 mol/L in children at which thromboembolic risk is reversed, lens subluxation is halted and bone growth in children proceeds normally.

• #1 Homocystinuria: Causes, Symptoms & Diagnosis

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

  How Is Homocystinuria Diagnosed? […] Your childs doctor may look for certain signs to determine whether you or your child has this condition. An extremely thin or tall child is more likely to have the condition. Additionally, their doctor may search for signs such as chest deformities, a curvature of the spine, and dislocated lenses in the eyes. An eye examination can reveal a dislocated lens if your child experiences double or significantly impaired vision. […] Your doctor may also order a series of tests to determine if your child is affected. These tests may include: […] genetic testing to look for one of the genes involved in the disorder […] an amino acid screen of the blood and urine to check for excess homocysteine […] a test to determine the bodys response to consuming methionine […] a liver biopsy and enzyme assay to check enzymatic activity. […] Other tests that may be done to determine the impact of the disease include X-rays to look for signs of osteoporosis, a skin biopsy, and a fibroblast culture.

• #1 SciELO Brazil – Diagnosis and Management of Classica Homocystinuria in Brazil: A Summary of 72 Late-Diagnosed Patients Diagnosis and Management of Classica Homocystinuria in Brazil: A Summary of 72 Late-Diagnosed Patients

  https://www.scielo.br/j/jiems/a/pFHcbtmVtLGGcZcCZK87jCk/?lang=en

  This study described a broad clinical characterization of classical homocystinuria (HCU) in Brazil. […] Most patients diagnosed with HCU in Brazil are late diagnosed, express a severe phenotype, and poor metabolic control. […] However, diagnosis and management of HCU is still a major challenge in developing countries, where newborn screening is unavailable and access to health-care services is often poor and unequal. […] Diagnosis was in general made on clinical symptoms followed by clear elevations in homocysteine and methionine. […] All 72 patients had delayed diagnoses: 62 patients had been diagnosed after clinical suspicion and biochemical findings consistent with HCU (hyperhomocysteinemia and hypermethioninemia), and the remaining 10 had been diagnosed on family screening. […] The main clinical findings leading to investigation of HCU are represented in Figure 1. Eye disease, the most prevalent symptom at diagnosis (67% of cases), accounted for 63% of referrals for HCU investigation.

• #1 Homocystinuria: Challenges in diagnosis and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2830775/

  Two patients with homocystinuria are discussed. Both patients presented with behavioural abnormalities and deficits in attention symptoms that are frequently encountered in paediatric office practice. In both cases, the diagnosis of homocystinuria was not made at initial presentation. Subtle but definite phenotypic features eventually provided the first indication of homocystinuria between the ages of five to seven years. Laboratory screening confirmed homocystine in the urine, and elevated methionine and homocysteine plasma levels in both patients. […] Without a high index of suspicion, physicians can easily overlook a diagnosis of homocystinuria. The management of patients with homocystinuria continues to pose a challenge to physicians and care givers. […] The present paper describes two patients in whom the diagnosis of homocystinuria was made after the early childhood years. The patients clinical features were nonspecific, but biochemical findings confirmed the diagnosis.

• #1 Homocystinuria: Causes, symptoms, and tests

  https://www.medicalnewstoday.com/articles/318526

  Clear signs that may lead a doctor to test for homocystinuria include a child being extremely thin and too tall for their age or not growing as expected. […] Additionally, the doctor will look for signs of chest deformity, spinal curvature, and dislocated eye lenses. […] Eye exams may reveal vision problems, while X-rays may show signs of weak bones. Genetic testing, amino acid screening, liver biopsies, and liver enzyme tests can also help a doctor confirm a diagnosis of homocystinuria. […] Researchers recommend genetic testing for anyone who has a family history of homocystinuria and wants to have children. […] However, because this condition is a result of a genetic mutation, it is not possible to prevent it. The only reason for genetic testing is to give people an idea of their risk of passing on a gene mutation that can lead to homocystinuria.

• #1 Homocystinuria: Challenges in diagnosis and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2830775/

  Delayed diagnosis of homocystinuria decreases the likelihood of optimal developmental outcome, and leads to an increased risk of systemic consequences. Earlier case detection, along with the introduction of a low methionine diet and pyridoxine supplements, is associated with a better prognosis, thus providing evidence for including the detection of homocystinuria in the newborn screening programs. […] The consideration of metabolic etiologies in the investigation of ADHD and developmental delay in the pre-school and childhood periods is essential for the early identification of patients with homocystinuria.

• #1 Homocystinuria/Homocysteinemia: Overview, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1115062-workup

  If patients present with systemic signs and symptoms, screening tests followed by confirmatory tests may be done. […] Laboratory studies may be considered in patients who present with symptoms of acute stroke in the absence of traditional risk factors such as hypertension, smoking, and diabetes. […] Whether a methionine challenge should be used for testing is not clear at this juncture. […] If homocystinuria is suspected on the basis of history, physical examination, and family history, the patient may be transferred to a tertiary care center, where expertise in a variety of relevant fields is more likely to be available.

• #1 Homocystinuria patient and caregiver survey: experiences of diagnosis and patient satisfaction | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-01764-x

  The diagnosis was made by newborn screening in 20% of patients and in 50% of the others within 1 year of the initial symptom but in 12.5% it took over 15 years. […] The delay was attributed mainly to ignorance of the disease. […] Even when the diagnosis is made, the way it is communicated is sometimes poor. […] There is often a long delay in diagnosing the homocystinurias unless this is achieved by newborn screening; this survey also highlights problems with the availability and cost of treatment and the palatability of protein substitutes. […] The diagnosis was made within a year of the first symptoms in half of the clinically ascertained patients in this survey but it was delayed by more than 15 years in 12.5% patients. […] The patients age at first presentation correlated with the diagnostic delay.

• #1 WV DHHR – OMCFH – Newborn Metabolic Screening – Homocystinuria

  https://www.wvdhhr.org/nbms/diseases/Homocystinuria.asp

  The term „homocystinuria” designates a biochemical abnormality, not a specific disease entity. […] The potential for early clinical diagnosis is limited. Ocular abnormalities, because of their distinctive lens displacement, may lead to the diagnosis. […] Quantitative serum or plasma amino acid determination is used for diagnosis of homocystinuria. Plasma amino acids show increased methionine and homocystine concentrations with reduced concentrations of cystine and absent cystathionine. […] Treatment depends on the underlying cause of homocystinuria. As a first step, pyridoxine (vitamin B6) responsiveness should be ascertained, because approximately 50% of patients respond to large doses of this vitamin. […] Increased concentrations of methionine may be minimal during the first 3 days of life until there is adequate protein intake (milk feedings). […] Programs continue to evaluate the efficacy of screening and early treatment. Improvement in screening to decrease the numbers of missed cases is important.

• #1 Classical homocystinuria

  https://www.healthywa.wa.gov.au/sitecore/content/Corporate/Articles/U_Z/WA-Newborn-Bloodspot-Screening-Program/Conditions-screened-for-in-WA/Classical-homocystinuria

  Classical homocystinuria is an amino acid disorder. It is a hereditary disease that is caused by a missing enzyme (cystathionine -synthase) that is required to metabolise methionine and homocysteine. […] Metabolites on bloodspot screening: Increased methionine, Increased homocysteine (second-tier test). […] Diagnostic tests: Plasma total homocysteine, Plasma amino acids, Urine amino and organic acids, CBS gene analysis. […] The vitamin B6-responsive form of CBS deficiency may be missed as methionine may not be increased in the first weeks of life.

• #1

  https://link.springer.com/article/10.1007/s10545-016-9979-0

  CBS deficiency is characterised biochemically by an accumulation of Hcy, decreased synthesis of cystathionine and cysteine and usually by increased Met. […] The major confounder that may mask the biochemical hallmarks of CBS deficiency is the intake of pyridoxine. […] The diagnosis can be masked in patients with mild disease who are taking pyridoxine or pyridoxine-fortified multivitamins and foods prior to biochemical testing. […] Confirmation of CBS deficiency cannot be based on a single method as each technique gives normal results in some patients with CBS deficiency. […] The gold standard for confirming CBS deficiency is generally considered to be the determination of cystathionine production from Hcy and serine in cultured fibroblasts using radioactive or deuterium labelled substrates.

• #1 SciELO Brazil – Diagnosis and Management of Classica Homocystinuria in Brazil: A Summary of 72 Late-Diagnosed Patients Diagnosis and Management of Classica Homocystinuria in Brazil: A Summary of 72 Late-Diagnosed Patients

  https://www.scielo.br/j/jiems/a/pFHcbtmVtLGGcZcCZK87jCk/?lang=en

  Current clinical and biochemical data were available for 44 patients, of whom 7 were responsive and 37 were nonresponsive to pyridoxine. […] Pyridoxine-responsive patients had significantly lower total homocysteine levels at study inclusion. […] The main strategies and goals of HCU treatment have been recently established in the first guidelines for the diagnosis and management of CS deficiency. […] Early diagnosis and early treatment are the key to prevent clinical manifestations and improve prognosis. […] In conclusion, this study provides the first broad clinical characterization of HCU in Brazil. All patients described here were late diagnosed, and most expressed a severe phenotype associated with nonresponsiveness to pyridoxine, early and multisystem clinical manifestations, and poor metabolic control.

• #1 Homocystinuria/Homocysteinemia: Overview, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1952251-overview

  Several studies have pointed out that early diagnosis and institution of treatment and dietary restriction is likely to slow the progression of disease in homocystinuria as well as to reverse some of the features. If family history and sibling history suggest homocystinuria, screening tests should be advised. […] If homocystinuria is suspected on the basis of history, physical examination, and family history, the patient may be transferred to a tertiary care center, where expertise in a variety of relevant fields is more likely to be available. […] The urine screening test for sulfur-containing amino acids, called the cyanide nitroprusside test, can be undertaken; however, high rates of false-negative as well as false-positive results are reported. […] A neonatal screening test, called the Guthrie test, detects high levels of methionine in heel-stick blood. This test is performed routinely in several states for detection of phenylalanine, leucine, and methionine. Because of high false-negative results in homocystinuric patients, a recent report suggested lowering the threshold of methionine to qualify as abnormal.

• #1

  https://link.springer.com/article/10.1007/s10545-016-9979-0

  Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. […] We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. […] Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 mol/L. […] We recommend keeping the concentration below 100 mol/L because levels fluctuate and the complications associated with high levels are so serious. […] The diagnosis is very likely if elevated tHcy is accompanied by high or borderline high plasma Met concentrations and further supported if sensitive methods demonstrate low plasma cystathionine concentrations with an increased Met-to-cystathionine ratio.

• #1 Homocystinuria – Child Neurology Foundation

  https://www.childneurologyfoundation.org/disorder/homocystinuria/

  Some forms of the disorder may get better after adding certain vitamins to the diet. This is especially true for milder forms of the disorder. Helpful vitamins include vitamins B6 and B12 as well as folate. […] There is a type of medication called betaine that can help some patients lower levels of homocysteine in the body. Betaine occurs naturally in the body and in many regular foods, such as beets and seafood. It usually causes only minor side effects. […] Patients with this disorder can do well with treatments that lower the level of homocysteine in the body. Treatments help to prevent some of the complications of the disease. They can help patients have normal development and growth. However, some patients will still have eye problems and blood clots. These patients will need to be closely monitored.

• #1 Homocystinuria | Amino Acid Metabolism Disorder – Causes, Symptoms, Diagnosis and Treatment

  https://www.medindia.net/health/conditions/homocystinuria-amino-acid-metabolism-disorder.htm

  How do you Diagnose Homocystinuria? Diagnosis is suspected during clinical examination and based on clinical suspicion diagnosis is confirmed by blood tests, imaging tests and skin biopsy. […] The diagnosis is suspected in persons/children with long, thin build, lens dislocation, glaucoma and developmental abnormalities. […] Increased levels of the aminoacids homocysteine and methionine in blood and urine. […] To confirm the diagnosis, CBS enzyme activity can be measured and will be low in a type of cell called fibroblast found in the connective tissue layer of the skin by obtaining a sample of skin, or from white blood cells (lymphocytes). These may not be needed in typical clinical presentation along with elevated aminoacid levels. […] X-rays of long bones and pelvis and dual-energy X-ray absorptiometry (DEXA) scan may demonstrate changes of premature osteoporosis (weak and porous bones). […] Genetic testing can be done to look for presence of the abnormal gene.

• #1 Orphanet: Homocystinuria without methylmalonic aciduria

  https://www.orpha.net/en/disease/detail/622

  Homocystinuria without methylmalonic aciduria is an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, encephalopathy and, sometimes, developmental delay, and associated with homocystinuria and hyperhomocysteinemia. […] Diagnosis is based on evidence of increased levels of homocystine in urine, and homocysteine or homocystine in plasma, and presence of megaloblastic anemia. Plasma methionine is frequently low. Genetic complementation analysis or identification of mutations in the MTR, MTRR or MMADHC genes can confirm the diagnosis. […] Prenatal diagnosis is possible by identification of elevated homocysteine in amniotic fluid or by biochemical studies of cultured amniocytes. Mutation analysis is possible when the disease causing mutations have been identified in the index case. Treatment of the mother of an affected fetus with cobalamin during pregnancy has been carried out, and appears to have been successful in preventing development of disease.

• #2 Classical homocystinuria – Genomics Education Programme

  http://www.genomicseducation.hee.nhs.uk/documents/classical-homocystinuria/

  Classical homocystinuria (HCU) is an autosomal recessive disorder caused by a deficiency in cystathionine -synthase (CBS) that results in a defect in the catabolic pathway of the amino acid methionine. […] Frontline biochemical testing for the diagnosis of classical HCU includes the measurement of total homocysteine accompanied by plasma amino acid analysis, typically performed by specialist metabolic laboratories. […] Diagnosis is characterised biochemically by markedly raised concentrations of plasma total homocysteine and methionine (as determined by plasma amino acid analysis). […] HCU may also be diagnosed by tandem mass-spectrometry analysis of methionine in dried blood spots as part of newborn screening programmes, for example the NHS newborn blood spot screening (NBS). […] Pyridoxine (vitamin B6) challenge is often performed following diagnosis, prior to the initiation of treatment.

• #2

  https://www.gov.uk/government/publications/hcu-suspected-description-in-brief/homocystinuria-hcu-detailed-information

  Homocystinuria (HCU) is a rare but treatable inherited metabolic disorder that prevents the normal breakdown of protein. […] When your baby was about 5 days old, your midwife took some blood from your baby’s heel for their newborn blood spot screening test (the heel prick test). The newborn blood spot screening test measures the amount of some amino acids in the blood. A high level of the amino acids methionine and total homocysteine suggests your baby may have HCU. This is called a screen positive result. […] If your baby has a screen positive result, you will be seen by a metabolic doctor, dietitian and nurse specialist (the metabolic team). The team will provide advice and support. Blood tests will be carried out to confirm or exclude the diagnosis of HCU. […] The metabolic team will see you regularly throughout your child’s life and your child will remain under their care. Your baby will need regular blood tests to monitor the levels of homocysteine in their blood.

• #2 Homocystinuria | Newborn Screening

  https://newbornscreening.hrsa.gov/conditions/homocystinuria

  Homocystinuria is an inherited (genetic) condition that prevents the body from processing proteins correctly. […] Newborn screening for homocystinuria is done using a small amount of blood collected from your baby’s heel. […] During screening, a special machine measures how much of certain amino acids, including methionine and homocysteine, are in your baby’s blood. […] If your baby’s blood spot screening result for homocystinuria is out-of-range, your baby’s health care provider will contact you. […] An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. […] You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems if they are not diagnosed and treated quickly.

• #2

  https://link.springer.com/article/10.1007/s10545-016-9979-0

  Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. […] We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. […] Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 mol/L. […] We recommend keeping the concentration below 100 mol/L because levels fluctuate and the complications associated with high levels are so serious. […] The diagnosis is very likely if elevated tHcy is accompanied by high or borderline high plasma Met concentrations and further supported if sensitive methods demonstrate low plasma cystathionine concentrations with an increased Met-to-cystathionine ratio.

• #2 WV DHHR – OMCFH – Newborn Metabolic Screening – Homocystinuria

  https://www.wvdhhr.org/nbms/diseases/Homocystinuria.asp

  The term „homocystinuria” designates a biochemical abnormality, not a specific disease entity. […] The potential for early clinical diagnosis is limited. Ocular abnormalities, because of their distinctive lens displacement, may lead to the diagnosis. […] Quantitative serum or plasma amino acid determination is used for diagnosis of homocystinuria. Plasma amino acids show increased methionine and homocystine concentrations with reduced concentrations of cystine and absent cystathionine. […] Treatment depends on the underlying cause of homocystinuria. As a first step, pyridoxine (vitamin B6) responsiveness should be ascertained, because approximately 50% of patients respond to large doses of this vitamin. […] Increased concentrations of methionine may be minimal during the first 3 days of life until there is adequate protein intake (milk feedings). […] Programs continue to evaluate the efficacy of screening and early treatment. Improvement in screening to decrease the numbers of missed cases is important.

• #2 Homocystinuria diagnosis and management: it is not all classical | Journal of Clinical Pathology

  https://jcp.bmj.com/content/75/11/744

  Testing for pyridoxine responsiveness forms an essential part of the diagnostic process for any patient newly diagnosed with HCU. […] In fully pyridoxine-responsive HCU, target tHCy can be attained with oral pyridoxine alone (table 2) typically with doses in excess of the recommended daily allowance, ranging from 300 to 900mg/day in adults and 10mg/kg/day to a maximum of 500mg/day in children. […] In non-pyridoxine-responsive HCU and some partially responsive patients, target tHCy can only be attained by additionally following a protein restricted diet to limit intake of the essential amino acid, methionine, the precursor to HCy production in the transsulphuration pathway. […] In all forms of HCU, routine supplementation with folate and vitamin B12 is advisable as a low risk non-evidence-based intervention to prevent nutritional deficiencies of these vitamins contributing to treatment resistance.

• #2 Homocystinuria – UF Health

  https://ufhealth.org/conditions-and-treatments/homocystinuria

  Homocystinuria is a genetic disorder that affects the metabolism of the amino acid methionine. […] Symptoms may occur as mildly delayed development or failure to thrive. Increasing visual problems may lead to diagnosis of this condition. […] If there is poor or double vision, an eye doctor (ophthalmologist) will perform a dilated eye exam to look for dislocation of the lens or nearsightedness. […] Tests that may be ordered include any of the following: Amino acid screen of blood and urine, Genetic testing, Homocysteine level, Liver biopsy and enzyme assay, Skeletal x-ray, Skin biopsy with a fibroblast culture, Standard ophthalmic exam. […] Although no cure exists for homocystinuria, vitamin B therapy can help about half of people affected by the condition. […] If the diagnosis is made in childhood, starting a low-methionine diet quickly may prevent some intellectual disability and other complications of the disease. […] Genetic counseling is recommended for people with a family history of homocystinuria who want to have children. Prenatal diagnosis of homocystinuria is available.

• #2 Homocystinuria | Amino Acid Metabolism Disorder – Causes, Symptoms, Diagnosis and Treatment

  https://www.medindia.net/health/conditions/homocystinuria-amino-acid-metabolism-disorder.htm

  How do you Diagnose Homocystinuria? Diagnosis is suspected during clinical examination and based on clinical suspicion diagnosis is confirmed by blood tests, imaging tests and skin biopsy. […] The diagnosis is suspected in persons/children with long, thin build, lens dislocation, glaucoma and developmental abnormalities. […] Increased levels of the aminoacids homocysteine and methionine in blood and urine. […] To confirm the diagnosis, CBS enzyme activity can be measured and will be low in a type of cell called fibroblast found in the connective tissue layer of the skin by obtaining a sample of skin, or from white blood cells (lymphocytes). These may not be needed in typical clinical presentation along with elevated aminoacid levels. […] X-rays of long bones and pelvis and dual-energy X-ray absorptiometry (DEXA) scan may demonstrate changes of premature osteoporosis (weak and porous bones). […] Genetic testing can be done to look for presence of the abnormal gene.

• #2 Homocystinuria

  https://dermnetnz.org/topics/homocystinuria

  How is homocystinuria diagnosed? […] Testing for homocystinuria can include: […] Cyanide-nitroprusside test […] Serum and urine amino acid screening […] Plasma levels of free methionine […] Ophthalmological exam for myopia, ectopic lentis […] Skin biopsy with fibroblast culture […] Skeletal X-ray […] Liver biopsy with enzyme assay […] MTHFR genotyping.

• #2 Diagnosis of Classic Homocystinuria in Two Boys Presenting with Acute Cerebral Venous Thrombosis and Neurologic Dysfunction after Normal Newborn Screening

  https://www.mdpi.com/2409-515X/7/3/48

  Homocystinuria, caused by cystathionine β-synthase deficiency, is a rare inherited disorder involving metabolism of methionine. […] The 14-month-old boy had normal newborn screening. The 7-year-old boy initially had an abnormal newborn screen for homocystinuria but second tier test that consisted of total homocysteine was normal, so his newborn screen was reported as normal. […] Methionine is the primary target in newborn screening for homocystinuria and total homocysteine is a secondary target. Screening is usually performed after 24–48 h of life in most states in the US and some states perform a second screen as a policy on all tested newborns or based on when the initial newborn screen was performed. […] It is universally known that methionine is a poor target and newborn screening laboratories have used different cutoffs for a positive screen.

Zobacz więcej