Materiały źródłowe

• #1 Isovaleric acidemia: Symptoms, causes, treatments, and more

  https://www.medicalnewstoday.com/articles/isovaleric-acidaemia

  Symptoms of IVA may develop throughout childhood. In severe cases, symptoms may appear within a few days after birth. […] However, the IVA symptoms can differ between people. Symptoms may also come and go. […] Within a few weeks of birth, symptoms might include: an odor of sweating feet while a newborn is ill, difficulties with feeding, an inability to gain weight. […] Symptoms of IVA also include: developmental delays, tremors and seizures, nausea and vomiting, low muscle tone, low energy. […] Infants with the acute form of IVA may have more severe symptoms from birth. A metabolic crisis can present with the following symptoms: low energy, vomiting, sleepiness, irritability, floppiness and balance loss, difficulties with feeding, breathing problems. […] This is a medical emergency. Without treatment, a metabolic crisis can lead to convulsions, where the muscles contract uncontrollably, and coma. It can also be fatal. […] A chronic intermittent type of IVA might also present. This leads to symptoms that occur and then resolve. […] According to a 2012 study of 176 people with IVA, the diagnosis of IVA symptoms near birth usually has links to an increased risk of developmental delays and mortality.

• #1 Isovaleric acidemia – Wikipedia

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

  A characteristic feature of isovaleric acidemia is a distinctive odor of sweaty feet. This odor is caused by the buildup of a compound called isovaleric acid in affected individuals. […] In about half of cases, the signs and symptoms of this disorder become apparent within a few days after birth and include poor feeding, vomiting, seizures, and lack of energy that can progress to coma. These medical problems are typically severe and can be life-threatening. In the other half of cases, the signs and symptoms of the disorder appear during childhood and may come and go over time. They are often triggered by an infection. […] A 2011 review of 176 cases found that diagnoses made early in life (within a few days of birth) were associated with more severe disease and a mortality of 33%. Children diagnosed later, and who had milder symptoms, showed a lower mortality rate of ~3%.

• #1 IVA (isovaleric acidemia) – newbornscreening.info

  https://www.newbornscreening.info/iva-isovaleric-acidemia/

  The effects of IVA vary from person to person. There are two main types of IVA. About half of all babies start showing symptoms shortly after birth. The other type called chronic-intermittent, starts later in infancy or childhood. […] Babies with IVA seem healthy at birth. Often, the first symptoms start between one day and two weeks of age. […] IVA causes episodes of illness called metabolic crises. Some of the first symptoms of a metabolic crisis are: poor appetite, extreme sleepiness or lack of energy, vomiting, problems staying warm, an odor similar to sweaty feet. […] Other symptoms can then follow: increased levels of acidic substances in the blood, called metabolic acidosis, high levels of ammonia in the blood, ketones in the urine, low platelets, low level of white blood cells, seizures, swelling of the brain, bleeding in the brain, coma, sometimes leading to death.

• #1 Clinical and neurocognitive outcome in symptomatic isovaleric acidemia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-9

  The only patient who was severely mentally retarded was diagnosed late at the age of 6.5 years. […] Mortality in the early diagnosis group was 33% during the initial episode of severe metabolic acidosis. […] In the early diagnosis group, the mean age at onset of symptoms as reported for 55 of 81 cases, was 6.8 5.4 days (mean SD; median 6 days). […] Amongst them, 20 patients who died during the initial catabolic episode had a significantly earlier onset of symptoms (mean SD: 4.6 2.9 days; median 3.5 days) than 35 patients who survived this initial catabolic episode. […] In patients diagnosed late, the mortality rate was only 3%. […] Of patients with an early diagnosis and treatment, 85% (39/46) had a normal cognitive outcome, whereas only 45% (28/62) of patients with a late diagnosis had a normal cognitive outcome.

• #1 Isovaleric acidemia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/isovaleric-acidemia/

  Isovaleric acidemia is a rare disorder in which the body is unable to properly break down a particular protein building block (amino acid). […] Health problems related to isovaleric acidemia range from very mild to life-threatening. In severe cases, the features of isovaleric acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, seizures, and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including seizures, coma, and possibly death. […] In other cases, the signs and symptoms of isovaleric acidemia appear during childhood and may come and go over time. Children with this condition may fail to gain weight and grow at the expected rate (failure to thrive) and often have delayed development. In these children, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), infections, or eating an increased amount of protein-rich foods.

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

  https://www.babysfirsttest.org/newborn-screening/conditions/isovaleric-acidemia

  Isovaleric acidemia (IVA) is an inherited condition in which the body is unable to break down certain proteins properly. […] If untreated, IVA can cause brain damage and even death. […] Signs of IVA include: Poor appetite, Sleeping longer or more often, Tiredness, Vomiting, A sweaty feet smell, Seizures. […] Without treatment, babies with isovaleric acidemia (IVA) can suffer brain damage or even die within the first year of life. […] With early and careful treatment, your child will most likely have a healthy life with typical growth and development.

• #1 Clinical and neurocognitive outcome in symptomatic isovaleric acidemia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-9

  57% of study patients (12/21) were diagnosed within the first weeks of life and 43% (9/21) in childhood. […] An acute metabolic attack was the main cause of diagnostic work-up. […] 44% of investigated study patients (7/16) showed mild motor dysfunction and only 19% (3/16) had cognitive deficits. […] The patients’ intelligence quotient was not related to the number of catabolic episodes but was inversely related to age at diagnosis. […] In published cases, mortality was high (33%) if associated with neonatal diagnosis, following manifestation at an average age of 7 days. […] The clinical presentation of IVA appears to be highly variable ranging from severely affected to asymptomatic subjects. […] It may present either in the neonatal period as an acute episode of fulminant metabolic acidosis which may lead to coma and death („acute neonatal form”) or later as a „chronic intermittent form” associated with developmental delay, with or without recurrent acidotic episodes during catabolic stress.

• #1 Aspects of Newborn Screening in Isovaleric Acidemia

  https://www.mdpi.com/2409-515X/4/1/7

  Mortality is highest in patients with an early clinical onset: an analysis of 155 published patients with symptomatic IVA showed a mortality rate of about one-third during the initial metabolic crisis in patients diagnosed within the first five weeks of life, whereas patients diagnosed thereafter had a low mortality rate of only 3%. […] Early initiation of treatment in IVA, i.e., starting therapy during the first weeks of life, was shown to decrease the frequency of severe ketoacidotic crises and was associated with an overall good clinical outcome.

• #1 IVA (isovaleric acidemia) – newbornscreening.info

  https://www.newbornscreening.info/iva-isovaleric-acidemia/

  If not treated, many babies die during their first metabolic crisis. In those who survive, repeated episodes of metabolic crisis can cause brain damage. This can result in life-long learning problems or intellectual disabilities. […] Symptoms often start around one year of age. Some children, though, do not have symptoms until later in childhood. […] Episodes of metabolic crisis can be brought on by illness, infection, or by eating large amounts of protein. When a child is ill, body protein is broken down for energy. In a child with IVA, this can cause high levels of isovaleric acid and results in a metabolic crisis. […] Between episodes of metabolic crisis, children with IVA are usually healthy. […] Even when treated, some children still have repeated bouts of metabolic crisis. This can lead to life-long learning problems or intellectual disabilities. As they get older, children tend to have fewer metabolic crises.

• #1 Isovaleric Acidemia — New England Consortium of Metabolic Programs

  https://www.newenglandconsortium.org/isova

  The neonatal form presents within the first days of life with a life-threatening picture of severe lethargy progressing to obtundation. The infantile or late-onset form has a more insidious presentation with failure to thrive, developmental delay, and perhaps other neurologic features such as seizures and spasticity. […] In both presentations, the characteristic pungent odor of IVA may be present on the body and in the blood. […] An acute metabolic decompensation in a patient with IVA is almost always precipitated by a stressor, such as infection, injury, surgery, hormonal changes, or significant dietary changes (involving increased protein intake). […] Acute pancreatitis: One should be aware of this sequela and check a serum amylase and lipase levels if there are any signs that indicate the possibility of acute pancreatitis. […] Stroke: Any neurologic deterioration in a patient with IVA in metabolic crisis should be addressed emergently as the risk of neurologic stroke is higher in this patient population.

• #1 NEWBORN SCREENING

  http://w.newbornscreening.info/Parents/organicaciddisorders/IVA.html

  With prompt and careful treatment, children with IVA have a good chance to live healthy lives with typical growth and development. […] Even when treated, some children still have repeated bouts of metabolic crisis. This can lead to life-long learning problems or intellectual disabilities. As they get older, children tend to have fewer metabolic crises.

• #1 Isovaleric Acidemia — New England Consortium of Metabolic Programs

  https://www.newenglandconsortium.org/isova

  Isovaleric acidemia (IVA,) also known as the sweaty foot syndrome, is an autosomal recessively inherited organic acid disorder due to a defect in the mitochondrial FAD-dependent enzyme isovaleryl-CoA dehydrogenase. […] In acute illness in IVA, isovaleric acid and its derivatives accumulate and profound metabolic acidosis (due to ketone body production and organic acid accumulation), hypoglycemia, and hyperammonemia ensue. […] The ketoacidosis, hyperammonemia, and hypoglycemia can explain the lethargy and obtundation that are sometimes seen in IVA patients in acute crisis. The ketoacidosis also produces vomiting. […] Acute Presentation: Lethargy, altered mental status […] Nausea, vomiting […] Hepatomegaly […] Characteristic pungent (sweaty feet) body odor (from the accumulated isovaleric acid).

• #1 Isovaleric acidaemia

  https://www.nhs.uk/conditions/isovaleric-acidaemia/

  Babies with IVA are unable to fully break down the amino acid leucine. […] Without treatment, severe and life-threatening symptoms can develop in some children, including seizures (fits) or falling into a coma. Some children with untreated IVA are also at risk of brain damage and developmental delay. […] The symptoms of IVA aren’t the same for everyone with the condition and some people may have more severe or frequent symptoms. […] Symptoms sometimes appear within the first few days or weeks after birth and may include: developing a distinctive odour of „sweaty feet”, poor feeding or loss of appetite, weight loss. […] Babies with IVA may also have episodes known as a metabolic crisis. Symptoms of a metabolic crisis include: lack of energy, vomiting, irritability, sleepiness and non-responsiveness, floppiness and falling over, poor feeding, breathing difficulties. […] It’s important to get medical help immediately if your baby develops symptoms of a metabolic crisis. […] In some cases, a metabolic crisis may be triggered later in childhood by an infection or illness.

• #1

  https://www.gov.uk/government/publications/iva-is-suspected-description-in-brief/isovaleric-acidaemia-iva-detailed-information

  Isovaleric acidaemia (pronounced iso-val-air-ik acid-ee-mia), or IVA, is a rare but treatable inherited metabolic disorder that prevents the normal breakdown of protein. […] Untreated IVA can cause long-term health problems, including brain damage, but with newborn screening and early treatment this can be prevented. […] Symptoms of a metabolic crisis include: irritability, sleepiness and non-responsiveness, floppiness and falling over, poor feeding, breathing difficulties, seizures, coma. […] A metabolic crisis can lead to serious illness and long-term brain damage, and can be life-threatening. […] With treatment, the outcome is usually very good and most children with IVA will avoid any long-term health problems.

• #1 Isovaleric Acidemia Presenting as Diabetic Ketoacidosis: A Case Report – Journal of Clinical Research in Pediatric Endocrinology

  https://jcrpe.org/articles/isovaleric-acidemia-presenting-as-diabetic-ketoacidosis-a-case-report/doi/Jcrpe.1181

  Untreated episodes of metabolic crises may lead to death or severe neurological sequelae. […] The first attack of metabolic crisis in our patient occurred at the age of two years and was triggered by a gastrointestinal infection. […] Clinical and laboratory findings led us to an initial diagnosis of DKA. However, no improvement in encephalopathy occurred in spite of intravenous fluids and insulin therapy. […] Detection of typical metabolites in blood and urine and mutation screening analyses confirmed the diagnosis of IVA. […] The treatment of acute metabolic decompensation in IVA cases comprises a high-caloric infusion therapy, correction of the metabolic acidosis and supplementation with L-carnitine and L-glycine to enhance the detoxification of isovaleric acid. […] This case illustrates that organic acidemias should be kept in mind in the differential diagnosis of DKA.

• #1 2025 ICD-10-CM Diagnosis Code E71.110: Isovaleric acidemia

  https://www.icd10data.com/ICD10CM/Codes/E00-E89/E70-E88/E71-/E71.110

  Clinical Information […] Signs and symptoms vary from very mild to life threatening and include vomiting, seizures, lethargy, and coma. […] clinical signs include severe acidosis and ketosis, lethargy, convulsions, pernicious vomiting, thrombocytopenia, neutropenia, and pancytopenia.

• #1 Isovaleric acidemia – Knowledge and References – Taylor & Francis

  https://taylorandfrancis.com/knowledge/Medicine_and_healthcare/Endocrinology/Isovaleric_acidemia/

  Isovaleric acidemia is a genetic disorder that is inherited in an autosomal recessive manner. It is caused by a deficiency of the mitochondrial enzyme isovaleryl-coenzyme A dehydrogenase, which is involved in the breakdown of the amino acid leucine. This deficiency leads to the accumulation of isovaleric acid in the body, which can cause a range of symptoms including vomiting, seizures, and developmental delays. […] Most patients develop vomiting, acidosis, lethargy, and coma in the newborn period, while others have these symptoms only associated with an underlying illness. […] Elevated levels of C5 acylcarnitine are characteristic of isovaleric acidemia with clinical features suggestive of significant motor delay.

• #1 IVD Gene Isovaleric acidemia NGS Genetic Test Cost 20000 INR in India

  https://dnalabsindia.com/test/ivd-gene-isovaleric-acidemia-ngs-genetic-dna-test

  IVD gene isovaleric acidemia is an inherited disorder that affects the breakdown of the amino acid leucine in the body. The condition is caused by a mutation in the IVD gene, which provides instructions for making an enzyme that breaks down leucine. Without this enzyme, leucine and its byproducts build up in the body, leading to a wide range of symptoms and potential health problems. […] Symptoms of IVD gene isovaleric acidemia can vary widely from person to person and can range from mild to severe. Some of the common symptoms include: Poor feeding, Vomiting, Lethargy, Seizures, Developmental delays, Intellectual disability, Behavioral problems, Enlarged liver, Musty or sweaty odor. […] IVD gene isovaleric acidemia is a rare genetic disorder that can cause a wide range of symptoms and potential health problems. Early diagnosis and treatment are essential to prevent complications and improve outcomes.

• #1 Classic Isovaleric Acidemia – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK601614/

  Individuals with clinical manifestations of isovaleric acidemia (IVA) have either classic IVA identified on newborn screening or classic IVA with a later diagnosis due to a missed diagnosis or later onset of clinical manifestations. Classic IVA is characterized by acute metabolic decompensations (vomiting, poor feeding, lethargy, hypotonia, seizures, and a distinct odor of sweaty feet). […] Clinical deterioration often occurs within hours to days after birth. Additional manifestations of classic IVA include developmental delay, intellectual disability and/or impaired cognition, epilepsy, and movement disorder (tremor, dysmetria, extrapyramidal movements). Early treatment in those identified by newborn screening can significantly reduce morbidity and mortality in individuals with classic IVA.

• #1 Clinical and neurocognitive outcome in symptomatic isovaleric acidemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3292949/

  Despite its first description over 40 years ago, knowledge of the clinical course of isovaleric acidemia (IVA), a disorder predisposing to severe acidotic episodes during catabolic stress, is still anecdotal. […] The clinical presentation of IVA appears to be highly variable ranging from severely affected to asymptomatic subjects. It may present either in the neonatal period as an acute episode of fulminant metabolic acidosis which may lead to coma and death („acute neonatal form”) or later as a „chronic intermittent form” associated with developmental delay, with or without recurrent acidotic episodes during catabolic stress. […] An acute metabolic attack was the main cause of diagnostic work-up. 44% of investigated study patients (7/16) showed mild motor dysfunction and only 19% (3/16) had cognitive deficits.

• #1 Clinical and neurocognitive outcome in symptomatic isovaleric acidemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3292949/

  The patients’ intelligence quotient was not related to the number of catabolic episodes but was inversely related to age at diagnosis. […] In published cases, mortality was high (33%) if associated with neonatal diagnosis, following manifestation at an average age of 7 days. […] The potential to avoid neonatal mortality and to improve neurologic and cognitive outcome under early treatment reinforces IVA to be qualified for newborn screening. […] Analyzing the course of 155 cases with clinically evident IVA published over a period of more than 40 years, we found that the mortality in neonates during their initial catabolic episode was high, with 30% much higher than during catabolic episodes in patients who were diagnosed later during infancy or childhood. […] Looking at the psychomotor development and neurocognitive outcome in later life, study patients who survived an acute neonatal manifestation appear to benefit from early diagnosis and start of therapeutic measures including a protein-restricted diet and carnitine/glycine supplementation.

• #1 Clinical and neurocognitive outcome in symptomatic isovaleric acidemia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-9

  The cognitive performance in terms of IQ was obtained in 13 of the 16 step II participants aged 5 to 24 years, whereas younger children were evaluated using DDST. […] Besides cognitive impairment in the three retarded patients mentioned above (3/16, 19%), we identified one patient with a known diagnosis of a learning disability to be in the low-normal IQ range. […] However, there was a significant inverse relationship between the IQ score and age at diagnosis (in days) in patients with not more than one severe catabolic episode. […] When subgrouped according to age at diagnosis, normal cognitive abilities (IQ scores) including academic performance (absence of a learning disability) were evident in 82% (9/11) of the early diagnosed study patients compared to only 44% (4/9) of late diagnosed study patients.

• #1

  https://www.gov.uk/government/publications/iva-is-suspected-description-in-brief/isovaleric-acidaemia-iva-mild-iva

  Isovaleric acidaemia (pronounced iso-val-air-ik acid-ee-mia), or IVA, is a rare but treatable inherited metabolic disorder that prevents the normal breakdown of protein. […] The 932CT variant is a mild form of IVA. The risk of problems for babies with this variant is much lower than for those with the more serious variant of the disorder. Babies with mild IVA do not normally develop symptoms or need treatment while well. […] If your baby becomes unwell, they might have an episode known as a metabolic crisis (also known as metabolic decompensation). This is caused by a rapid build-up of isovaleric acid and other related substances in their body, which can make them severely unwell. Symptoms of a metabolic crisis include: irritability, sleepiness and non-responsiveness, floppiness and falling over, poor feeding, breathing difficulties, seizures, coma. […] With prompt use of the emergency regimen, the outcome is very good and most children with mild IVA will avoid any long-term health problems.

• #1 Isovaleric acidemia | MedLink Neurology

  https://www.medlink.com/articles/isovaleric-acidemia

  In the chronic intermittent form of isovaleric acidemia, children have recurrent metabolic crises because of high intake of protein or minor infections that induce a catabolic state. […] Acute metabolic decompensation may be triggered by fasting, febrile illness (eg, gastroenteritis), or increased protein intake. […] The disorder may rarely present with a first acute metabolic decompensation in adulthood. […] Clinical and neurocognitive outcomes in isovaleric acidemia patients depend on early diagnosis and treatment. […] If treatment is initiated before the development of severe metabolic decompensation, the patients prognosis is significantly improved. […] Patients identified by newborn screening who carry a common missense mutation c.932CT (p.Ala282Val) are usually asymptomatic and most likely do not need treatment. […] Early diagnosis is crucial. The patients prognosis is significantly improved if treatment can be initiated before the first severe metabolic decompensation. Individuals who receive treatment before becoming symptomatic usually have normal long-term psychomotor development.

• #1 Frontiers | Analysis of the genotype–phenotype correlation in isovaleric acidaemia: A case report of long-term follow-up of a chinese patient and literature review

  https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.928334/full

  The child was prescribed a low-protein diet supplemented with L-carnitine. During the 8-year follow-up, no metabolic disorder or encephalopathic symptoms recurred. At present, the child is 11 years of age and has normal mental and motor performance. […] The prevalence of clinical manifestation of different clinical types is listed in Table 2, with no gender difference. The prevalence of vomiting in the chronic intermittent type was higher than that in the acute neonatal type, and the prevalence of sweaty foot odor in the chronic intermittent type was lower than that in the acute neonatal type. […] The clinical manifestations and prognosis of IVA vary greatly, and some patients die in the neonatal period. However, many asymptomatic patients are found through family or neonatal screening and remain asymptomatic during the follow-up. In the last follow-up, 12/68 had died and 56/68 had survived, 34 of whom developed normally without other complications. In total, twenty-two cases had developmental/mental impairment, other neurological disorders, and paroxysmal metabolic disorders. Early diagnosis and treatment have been reported that cannot prevent the onset of metabolic crisis but can prevent mental impairment. […] Therefore, the correlation between genotype and phenotype can help us understand the disease and guide genetic counseling, and early screening and diagnosis as early as possible for IVA can guide treatment and improve prognosis.

• #1 Clinical and neurocognitive outcome in symptomatic isovaleric acidemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3292949/

  When the overall neurocognitive outcome of the disorder is considered, it appears less devastating compared to other „classical” organic acidemias/acidurias such as methylmalonic aciduria (MMA) and propionic acidemia. […] No significant long-term complications beyond the central nervous system (CNS) involvement – mild motor dysfunction and cognitive deficits – were evident in our study patient population. […] The neurocognitive outcome is not related to the number of catabolic episodes.

• #1 Long Term Follow-Up of Polish Patients with Isovaleric Aciduria. Clinical and Molecular Delineation of Isovaleric Aciduria

  https://www.mdpi.com/2075-4418/10/10/738

  Our analysis revealed that neurocognitive outcome in individuals with neonatal manifestation and early introduction of treatment was more promising than in patients diagnosed during or after metabolic decompensation. […] In early-diagnosed patients, metabolic decompensations, if any, were milder and did not cause severe complications.

• #1 Aspects of Newborn Screening in Isovaleric Acidemia

  https://www.mdpi.com/2409-515X/4/1/7

  Isovaleric acidemia (IVA), an inborn error of leucine catabolism, is caused by mutations in the isovaleryl-CoA dehydrogenase (IVD) gene, resulting in the accumulation of derivatives of isovaleryl-CoA including isovaleryl (C5)-carnitine, the marker metabolite used for newborn screening (NBS). […] The phenotypical spectrum of IVA is wide and has been further broadened by NBS. Available data suggests that early diagnosis by NBS may improve the clinical outcome of IVA, as supported by reports of less frequent relapsing episodes of metabolic decompensation and short-term improvement of neurodevelopmental symptoms, even though studies on the long-term outcome of screened patients are still lacking. […] Two clinical phenotypes have been observed in unscreened patients. They may become symptomatic within the first days or weeks of life, presenting with poor feeding or vomiting and severe metabolic acidosis accompanied by neurological signs including lethargy, potentially progressing to coma or death.

• #1 Isovaleric Acidemia (IVA) – Baby Detect

  https://babydetect.com/en/isovaleric-acidemia-iva/

  All patients are prone to intermittent acute episodes of decompensation with minor illnesses. Childhood onset metabolic acidosis is typically brought on by prolonged fasting, increased intake of protein-rich food or infections, and can be fatal if not treated immediately. […] The characteristic smell of isovaleric acid may be present and is likened to sweaty feet/body sweat. Though severe developmental delay and neurologic sequelae are present in some patients, they are likely related to severe biochemical presentations. […] Prognosis for patients diagnosed by newborn screening is excellent with the potential for normal neurodevelopmental outcome with appropriate metabolic management. […] Patients who present symptomatically can have significant neurologic sequelae including neurodevelopmental delay, especially if acidosis and hyperammonemia are severe. So compliance with dietary treatment saves lives.

• #1 Genotype and phenotype characterization in a Spanish cohort with isovaleric acidemia | Journal of Human Genetics

  https://www.nature.com/articles/jhg2016144

  Isovaleric acidemia (IVA) is a rare disorder of leucine metabolism. […] The clinical manifestations of IVA are highly variable and range from a complete absence of symptoms to severe involvement. Three characteristic phenotypes have been identified: asymptomatic presentation, a chronic intermittent form with onset in infancy or childhood, and an acute neonatal form with early onset of metabolic decompensation that can lead to coma and death. Chronic intermittent IVA is frequently associated with developmental delay and/or failure to thrive and optic nerve atrophy. A distinctive sweaty feet odor is a presenting symptom in almost all patients at diagnosis. […] Based on the biochemical and clinical data, eight patients had mild/asymptomatic IVA, four had chronic intermittent IVA and four had acute neonatal IVA.

• #1

  https://omim.org/entry/243500

  Isovaleric acidemia (IVA) is an inborn error of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase. It can present with severe neonatal ketoacidosis leading to death, but in milder cases recurrent episodes of ketoacidosis of varying degree occur later in infancy and childhood. […] Two forms of isovaleric acidemia are recognized: the acute neonatal form, leading to massive metabolic acidosis from the first days of life and rapid death, and a chronic form in which periodic attacks of severe ketoacidosis occur with asymptomatic intervening periods. […] Budd et al. (1967) observed brother and sister who, before the age of 6 months, showed retarded psychomotor development, a peculiar odor resembling sweaty feet, an aversion to dietary protein, and pernicious vomiting, leading to acidosis and coma.

• #2 Classic Isovaleric Acidemia – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK601614/

  Individuals with clinical manifestations of isovaleric acidemia (IVA) have either classic IVA identified on newborn screening or classic IVA with a later diagnosis due to a missed diagnosis or later onset of clinical manifestations. Classic IVA is characterized by acute metabolic decompensations (vomiting, poor feeding, lethargy, hypotonia, seizures, and a distinct odor of sweaty feet). […] Clinical deterioration often occurs within hours to days after birth. Additional manifestations of classic IVA include developmental delay, intellectual disability and/or impaired cognition, epilepsy, and movement disorder (tremor, dysmetria, extrapyramidal movements). Early treatment in those identified by newborn screening can significantly reduce morbidity and mortality in individuals with classic IVA.

• #2 Isovaleric acidemia | MedLink Neurology

  https://www.medlink.com/articles/isovaleric-acidemia

  Isovaleric aciduria due to isovaleryl-CoA dehydrogenase deficiency presents with two distinct phenotypes: (1) acute neonatal onset with severe metabolic crisis that, without appropriate treatment, quickly evolves into coma and death or (2) a chronic intermittent disease with episodes of metabolic acidosis and psychomotor retardation. […] The disease may manifest in the neonatal period with a severe metabolic crisis that, without appropriate treatment, quickly evolves into coma and death. Alternatively, patients may have a chronic intermittent disease with episodes of metabolic acidosis. […] During metabolic crises, patients develop the typical features of an organic acid disorder with acidosis, ketosis, vomiting, progressive alteration of consciousness, and, without appropriate therapy, overwhelming illness, deep coma, and death.

• #2 Genotype and phenotype characterization in a Spanish cohort with isovaleric acidemia | Journal of Human Genetics

  https://www.nature.com/articles/jhg2016144

  Isovaleric acidemia (IVA) is a rare disorder of leucine metabolism. […] The clinical manifestations of IVA are highly variable and range from a complete absence of symptoms to severe involvement. Three characteristic phenotypes have been identified: asymptomatic presentation, a chronic intermittent form with onset in infancy or childhood, and an acute neonatal form with early onset of metabolic decompensation that can lead to coma and death. Chronic intermittent IVA is frequently associated with developmental delay and/or failure to thrive and optic nerve atrophy. A distinctive sweaty feet odor is a presenting symptom in almost all patients at diagnosis. […] Based on the biochemical and clinical data, eight patients had mild/asymptomatic IVA, four had chronic intermittent IVA and four had acute neonatal IVA.

• #2 Isovaleric acidaemia

  https://www.nhs.uk/conditions/isovaleric-acidaemia/

  Babies with IVA are unable to fully break down the amino acid leucine. […] Without treatment, severe and life-threatening symptoms can develop in some children, including seizures (fits) or falling into a coma. Some children with untreated IVA are also at risk of brain damage and developmental delay. […] The symptoms of IVA aren’t the same for everyone with the condition and some people may have more severe or frequent symptoms. […] Symptoms sometimes appear within the first few days or weeks after birth and may include: developing a distinctive odour of „sweaty feet”, poor feeding or loss of appetite, weight loss. […] Babies with IVA may also have episodes known as a metabolic crisis. Symptoms of a metabolic crisis include: lack of energy, vomiting, irritability, sleepiness and non-responsiveness, floppiness and falling over, poor feeding, breathing difficulties. […] It’s important to get medical help immediately if your baby develops symptoms of a metabolic crisis. […] In some cases, a metabolic crisis may be triggered later in childhood by an infection or illness.

• #2 Classic Isovaleric Acidemia – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK601614/

  Acute metabolic decompensations in individuals with classic IVA can occur either early in the neonatal period or later in life. These life-threatening episodes are typically triggered by fasting, (febrile) illness (especially gastroenteritis), or increased protein intake. During metabolic decompensation, individuals may exhibit various manifestations reflecting metabolic derangement (partially compensated metabolic acidosis, elevated lactate, ketosis, hyperammonemia), including vomiting, poor feeding, lethargy, hypotonia, seizures, and a distinct odor of sweaty feet. […] Individuals with classic IVA not identified by NBS usually develop the first manifestations of acute metabolic decompensation after a short symptom-free period after birth. Clinical deterioration often occurs within hours to days after birth with feeding refusal, recurrent vomiting, progressive weight loss, generalized hypotonia, abnormal posturing, and abnormal movements, and a distinctive odor of sweaty feet can be present. Laboratory abnormalities include severe metabolic acidosis with elevated anion gap, elevated lactate, ketosis, and hyperammonemia. […] Early diagnosis and treatment in those who survive the initial metabolic decompensation tends to result in better neurocognitive outcomes.

• #2 Isovaleric Acidaemia – Metabolic Support UKAccessibility ToolsIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://metabolicsupportuk.org/condition/isovaleric-acidaemia/

  Isovaleric Acidaemia presents differently in different people, and symptoms are not necessarily the same for everybody. […] Symptoms usually appear in the first few days of life and can include: Poor feeding, Vomiting, Seizures, Lack of energy (lethargy), A “sweaty feet” smell, especially during periods of illness. […] Later symptoms may also include not gaining weight or growing as expected (failure to thrive), and delayed development. […] Without adequate treatment, symptoms can worsen and progress into more serious health issues, causing repeated seizures, comas and, in extreme cases, death. […] In some cases, the symptoms of the disorder may appear to come and go during childhood. […] However, in the most severe cases, even when treatment is followed carefully, seizures and comas can occur and cause damage that leads to intellectual or learning disabilities.

• #2 Isovaleric acidemia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/isovaleric-acidemia/

  Isovaleric acidemia is a rare disorder in which the body is unable to properly break down a particular protein building block (amino acid). […] Health problems related to isovaleric acidemia range from very mild to life-threatening. In severe cases, the features of isovaleric acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, seizures, and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including seizures, coma, and possibly death. […] In other cases, the signs and symptoms of isovaleric acidemia appear during childhood and may come and go over time. Children with this condition may fail to gain weight and grow at the expected rate (failure to thrive) and often have delayed development. In these children, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), infections, or eating an increased amount of protein-rich foods.

• #2 Isovaleric Acidemia Presenting as Diabetic Ketoacidosis: A Case Report – Journal of Clinical Research in Pediatric Endocrinology

  https://jcrpe.org/articles/isovaleric-acidemia-presenting-as-diabetic-ketoacidosis-a-case-report/doi/Jcrpe.1181

  Isovaleric acidemia (IVA) is characterized by periodic vomiting, lethargy, coma, ketoacidosis and a ‘sweaty feet’ odor. […] Clinical manifestations in the acute form include vomiting and severe acidosis in the first few days of life, followed by progression to lethargy, convulsions, coma and death if proper therapy is not initiated. […] In both forms, an acute episode of metabolic decompensation may occur during a catabolic state such as an infection. […] Most organic acidemias present in the newborn period as an acute episode of fulminant metabolic acidosis which may lead to coma and death if not treated adequately. […] Typical laboratory findings during metabolic crises are metabolic acidosis, hyperammonemia, ketonuria, hypo- or hyperglycemia, anemia, thrombocytopenia, neutropenia, or pancytopenia.

• #2 Isovaleric acidemia | MedLink Neurology

  https://www.medlink.com/articles/isovaleric-acidemia

  In the chronic intermittent form of isovaleric acidemia, children have recurrent metabolic crises because of high intake of protein or minor infections that induce a catabolic state. […] Acute metabolic decompensation may be triggered by fasting, febrile illness (eg, gastroenteritis), or increased protein intake. […] The disorder may rarely present with a first acute metabolic decompensation in adulthood. […] Clinical and neurocognitive outcomes in isovaleric acidemia patients depend on early diagnosis and treatment. […] If treatment is initiated before the development of severe metabolic decompensation, the patients prognosis is significantly improved. […] Patients identified by newborn screening who carry a common missense mutation c.932CT (p.Ala282Val) are usually asymptomatic and most likely do not need treatment. […] Early diagnosis is crucial. The patients prognosis is significantly improved if treatment can be initiated before the first severe metabolic decompensation. Individuals who receive treatment before becoming symptomatic usually have normal long-term psychomotor development.

• #2 Isovaleric Acidaemia (IVA) – Inherited Metabolic Disorders in Scotland

  https://www.imd.scot.nhs.uk/isovaleric-acidaemia-iva/

  Babies with IVA are at risk of developing the following symptoms: poor feeding, irritability, sleepiness, vomiting, breathing difficulties and fast breathing, coldness. […] Left untreated, babies with IVA can deteriorate, have fits and slip into a coma which can be life threatening. This is due to high levels of harmful substances in the body. […] When babies with IVA become ill, they might show symptoms of metabolic crisis. A metabolic crisis is a period of time when the effects of the condition make your child unwell. Some children with IVA do not develop symptoms of a metabolic crisis until later in their first year of life or later in childhood. Causes of a metabolic crisis can include an infection such as a stomach upset or vomiting illness.

• #2 Neonatal isovaleric acidemia in China: A case report and review of literature

  https://www.wjgnet.com/2307-8960/full/v9/i2/436.htm

  Isovaleric acidemia (IVA) is a rare autosomal recessive inherited organic acidemia caused by a genetic deficiency of isovaleryl-CoA dehydrogenase (IVD). Its morbidity is low, but mortality is high. There is no effective cure for this disease. Early identification of IVA using clinical features can significantly slow disease progression and reduce mortality. […] The clinical presentation of IVA appears to be highly variable ranging from severely affected to asymptomatic patients. Clinical features include poor feeding, vomiting, acidosis, ketosis, progressive alteration of consciousness, seizures and finally deep coma and death without appropriate therapy. The characteristic odor of sweaty feet caused by isovaleric acid is often noted during metabolic crisis. […] The clinical features included neonatal onset (25 cases), acute episode (24 cases), sweaty feet odor (17 cases), pancytopenia (19 cases) and hyperammonemia (14 cases), and 15 deaths were reported. Through the literature review, we found that most cases occurred during the neonatal period, and the mortality rate was high. Thus, it is important for clinicians to be aware of this disease.

• #2 | Myriad Prequel® Prenatal Screen

  https://myriad.com/womens-health/diseases/isovaleric-acidemia/

  Symptoms of the neonatal form are often observed in the first few weeks after birth and include feeding problems, high acidity of the blood and urine, and difficulty in maintaining proper body temperature. Untreated IVA can eventually result in bleeding of the brain (cerebral hemorrhage), seizures, and death. […] Symptoms of the childhood form of IVA are often observed at about 12 months of age. These symptoms are similar to the neonatal form but are triggered by stresses such as illness, fasting, or high-protein diets. In the absence of stresses to the body, there may be no symptoms. However, children with childhood IVA may have learning problems, reduced growth, and muscle weakness. […] Without early diagnosis and treatment, individuals with IVA may have damage to the brain and nervous system, intellectual and developmental disability, or in severe cases, death. If a person with IVA receives treatment, they are more likely to reach normal levels of growth, development, and intellectual ability. However, some individuals may experience a reduction in growth and development, learning disabilities, or even death, due to periodic episodes of high levels of isovaleric acid, primarily in response to stress. As a person with IVA ages, the frequency of such episodes decreases. […] Individuals with IVA without symptoms are more likely to live a normal lifespan.

• #2 Aspects of Newborn Screening in Isovaleric Acidemia

  https://www.mdpi.com/2409-515X/4/1/7

  Isovaleric acidemia (IVA), an inborn error of leucine catabolism, is caused by mutations in the isovaleryl-CoA dehydrogenase (IVD) gene, resulting in the accumulation of derivatives of isovaleryl-CoA including isovaleryl (C5)-carnitine, the marker metabolite used for newborn screening (NBS). […] The phenotypical spectrum of IVA is wide and has been further broadened by NBS. Available data suggests that early diagnosis by NBS may improve the clinical outcome of IVA, as supported by reports of less frequent relapsing episodes of metabolic decompensation and short-term improvement of neurodevelopmental symptoms, even though studies on the long-term outcome of screened patients are still lacking. […] Two clinical phenotypes have been observed in unscreened patients. They may become symptomatic within the first days or weeks of life, presenting with poor feeding or vomiting and severe metabolic acidosis accompanied by neurological signs including lethargy, potentially progressing to coma or death.

• #2 Frontiers | Analysis of the genotype–phenotype correlation in isovaleric acidaemia: A case report of long-term follow-up of a chinese patient and literature review

  https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.928334/full

  Isovaleric acidaemia (IVA), characterized by an acute metabolic crisis and psychomotor delay, is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD). […] The patient presented with encephalopathic symptoms, such as vomiting, lethargy, and somnolence. […] The cardinal symptoms included vomiting, lethargy, “sweaty foot” odor, poor feeding, developmental delay, and epilepsy. […] The clinical manifestations of IVA include paroxysmal vomiting, lethargy or altered mental status, epilepsy, poor feeding, developmental delay, severe metabolic acidosis, hyperammonaemia, ketosis, hyper- or hypoglycaemia, and cytopenia. A typical “sweaty foot” odor is often found in the acute phase. The absence or delay of treatment can result in death or developmental delay.

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