Materiały źródłowe

• #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 inclusion of IVA in NBS programs in many countries has broadened knowledge of the variability of the condition, whereas prior to NBS, two distinct clinical phenotypes were known, an “acute neonatal” and a “chronic intermittent” form. […] The first countries that introduced IVA to their NBS programs were Australia, where IVA was included in the New South Wales NBS program in 1998, and Germany, where it was first included in the Bavarian NBS program in 1999. […] Since then, it has been implemented in national NBS programs in about 30 countries worldwide, and most recently (2015), in England and Wales.

• #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) is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD), which catalyses the oxidation of isovaleryl-CoA to 3-methylcrotonyl-CoA during the third step of leucine catabolism. 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. IVA can be categorized into three subtypes: (1) Acute neonatal type: disease presents in the first 2 weeks after birth, including severe metabolic acidosis and encephalopathy, often accompanied by leukopenia, neutropenia, thrombocytopenia, electrolyte disturbances, and hypo- or hyperglycaemia. The patient may experience coma or death if not properly treated. (2) Chronic intermittent type: findings include psychomotor delay and paroxysmal metabolic disorder. During the metabolic crisis, clinical manifestations are similar to those of the acute neonatal type. (3) Asymptomatic type: findings include mild biochemical abnormalities.

• #3 Orphanet: Isovaleric acidemia

  https://www.orpha.net/en/disease/detail/33

  A rare, autosomal recessive, organic aciduria that is characterized by variable clinical presentation ranging from acute neonatal onset of metabolic decompensation to later onset of chronic, non-specific manifestations including failure to thrive and/or developmental delay. All patients are prone to intermittent, acute metabolic decompensation. During metabolic episodes, urine analysis demonstrates elevated isovaleric acid derivatives. […] Accurate data on the prevalence is not readily available. Best estimates come from newborn screening studies that estimate prevalence at birth between 1/50,000-150,000. […] 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.

• #4 Isovaleric acidemia: MedlinePlus GeneticsLock

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

  Isovaleric acidemia is estimated to affect at least 1 in 250,000 people in the United States. […] 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. […] In other cases, the signs and symptoms of isovaleric acidemia appear during childhood and may come and go over time. […] Some people with gene mutations that cause isovaleric acidemia are asymptomatic, which means they never experience any signs or symptoms of the condition.

• #5 Isovaleric acidemia | MedLink Neurology

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

  The worldwide incidence of isovaleric acidemia is 1:100,000 live births diagnosed by newborn screening and 1:280,000 among cases diagnosed after the onset of symptoms. […] Selective screening by analysis of organic acids in urine or tandem mass spectrometry has demonstrated the presence of isovaleric acidemia in different populations around the world. […] The diagnosis can be missed in countries where isovaleric acidemia is not part of population newborn screening. […] Reported cases to date do not suggest an ethnic predisposition. […] In a systematic review and meta-analysis, 22 population studies of isovaleric acidemia were identified, 17 of which utilized tandem mass spectrometry with a total population screened of 14,304,075, and five of which relied on clinical ascertainment of cases with a total population screened of 5,100,705. […] In summary, the worldwide incidence of isovaleric acidemia is 1:100,000 live births diagnosed by newborn screening and 1:280,000 among cases diagnosed after the onset of symptoms. Sensitivity was clearly improved using newborn screening approaches with tandem mass spectrometry.

• #6 Aspects of Newborn Screening in Isovaleric Acidemia

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

  Using a data set of 1.6 million newborns from Germany, the birth prevalence of IVA was calculated to be 1 in 67,000. […] Prevalences from other countries were reported to be lower, such as 1 in 660,000 in Taiwan or 1 in 105,000 in Portugal. […] An analysis of available evidence by Dionisi-Vici et al. showed a more than four times higher incidence of IVA in the screened population as compared to clinical diagnosis, suggesting that the phenotypic spectrum of IVA detected by NBS is different and may include individuals that would not have presented clinically. […] With NBS becoming an important part of pediatric preventive strategies worldwide, several diagnostic pitfalls have come to attention. […] The possibility of pre-symptomatic diagnosis through NBS and the apparent benefit that has been demonstrated for patients diagnosed and treated early make IVA an ideal candidate for NBS programs.

• #7 | Myriad Prequel® Prenatal Screen

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

  How Common Is Isovaleric Acidemia? The prevalence of IVA is 1 in 250,000 in the American population. The incidence of IVA is about 1 in 62,000 in the German population. […] Individuals with IVA need close monitoring by a physician during times of illness and may need to ensure adequate hydration and adopt a diet high in carbohydrates. Frequent monitoring of individuals with IVA is important to determine that proper growth, metabolism, and development is ongoing.

• #8 Aspects of Newborn Screening in Isovaleric Acidemia

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

  Using a data set of 1.6 million newborns from Germany, the birth prevalence of IVA was calculated to be 1 in 67,000. […] Prevalences from other countries were reported to be lower, such as 1 in 660,000 in Taiwan or 1 in 105,000 in Portugal. […] An analysis of available evidence by Dionisi-Vici et al. showed a more than four times higher incidence of IVA in the screened population as compared to clinical diagnosis, suggesting that the phenotypic spectrum of IVA detected by NBS is different and may include individuals that would not have presented clinically. […] With NBS becoming an important part of pediatric preventive strategies worldwide, several diagnostic pitfalls have come to attention. […] The possibility of pre-symptomatic diagnosis through NBS and the apparent benefit that has been demonstrated for patients diagnosed and treated early make IVA an ideal candidate for NBS programs.

• #9 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 is estimated to affect one out of every 230,000 babies born in the United States. […] Follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition. […] Because IVA is a genetic condition, you may want to talk with a genetics specialist.

• #10 Isovaleric acidemia – Wikipedia

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

  Isovaleric acidemia is estimated to affect at least 1 in 250,000 births in the United States.

• #11 Isovaleric acidaemia – Genomics Education Programme

  http://www.genomicseducation.hee.nhs.uk/documents/isovaleric-acidaemia/

  The prevalence of the condition is approximately 1 in 155,000, based on EU data. […] As part of the NHS newborn blood spot screening (NBS) programme in England, C5 aclycarnitine in dried blood spots is used as the initial diagnostic metabolite. […] Families should be referred for genetic counselling; this is particularly important in families where consanguineous marriage is customary as there may be implications for the wider family.

• #12 Aspects of Newborn Screening in Isovaleric Acidemia

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

  Using a data set of 1.6 million newborns from Germany, the birth prevalence of IVA was calculated to be 1 in 67,000. […] Prevalences from other countries were reported to be lower, such as 1 in 660,000 in Taiwan or 1 in 105,000 in Portugal. […] An analysis of available evidence by Dionisi-Vici et al. showed a more than four times higher incidence of IVA in the screened population as compared to clinical diagnosis, suggesting that the phenotypic spectrum of IVA detected by NBS is different and may include individuals that would not have presented clinically. […] With NBS becoming an important part of pediatric preventive strategies worldwide, several diagnostic pitfalls have come to attention. […] The possibility of pre-symptomatic diagnosis through NBS and the apparent benefit that has been demonstrated for patients diagnosed and treated early make IVA an ideal candidate for NBS programs.

• #13 Aspects of Newborn Screening in Isovaleric Acidemia

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

  Using a data set of 1.6 million newborns from Germany, the birth prevalence of IVA was calculated to be 1 in 67,000. […] Prevalences from other countries were reported to be lower, such as 1 in 660,000 in Taiwan or 1 in 105,000 in Portugal. […] An analysis of available evidence by Dionisi-Vici et al. showed a more than four times higher incidence of IVA in the screened population as compared to clinical diagnosis, suggesting that the phenotypic spectrum of IVA detected by NBS is different and may include individuals that would not have presented clinically. […] With NBS becoming an important part of pediatric preventive strategies worldwide, several diagnostic pitfalls have come to attention. […] The possibility of pre-symptomatic diagnosis through NBS and the apparent benefit that has been demonstrated for patients diagnosed and treated early make IVA an ideal candidate for NBS programs.

• #14 Azthena logo with the word Azthena

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

  Isovaleric acidemia is estimated to have a prevalence of around one in 100,000 persons. […] The prevalence varies in different parts of the world, ranging from 1 in 67,000 in Germany to 1 in 775,000 in Australia.

• #15 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 incidence in China is about 1 in 190000 diagnosed by neonatal MS/MS. […] 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. […] The clinical manifestations vary, and disease onset can range from the neonatal period to the adult period. […] Early diagnosis and treatment are necessary to prevent neonatal mortality and improve the neurologic and cognitive outcomes.

• #16 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. We carried out a multicenter study of IVA patients diagnosed by newborn screening (NBS) or symptoms clinics over a period of 28 years in Spain. IVA was detected by NBS in 8 patients (prevalence of 1/326629). The clinical manifestations of IVA are highly variable and range from a complete absence of symptoms to severe involvement. In Spain, 1306518 newborns were screened for IVA between January 2001 and December 2013. The detection of 8 cases by NBS in our series corresponds to a prevalence of 1/326629, which is similar to rates reported elsewhere. Expanded NBS with tandem mass spectrometry (MS/MS) and calculation of the ratio of C5 to octanoylcarnitine, butyrylcarnitine and propionylcarnitine in whole blood is now used to detect presymptomatic IVA. IVA detected by NBS appears to be associated with a mostly favorable clinical course, although long-term prognosis has yet to be established. IVG in urine at diagnosis is a good biochemical marker of prognosis, and in our series, all the patients with chronic intermittent or acute neonatal forms of IVA had an IVG level 3000mmol per mol creatinine on detection of the disease. Our findings suggest that mild forms detected at screening might not progress later in life. The above findings and observations reinforce the importance of NBS for IVA.

• #17 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

  Isovaleric acidemia (IVA, OMIM: 243500) is an autosomal recessive leucine inborn error of metabolism caused by the deficiency of mitochondrial isovaleryl-CoA dehydrogenase (IVD; EC 1.2.99.10), encoded by the IVD gene. It is one of the four “classical” organic acidemias: propionic (PA), methylmalonic (MMA), glutaric (GA), and IVA, with a prevalence 1–9/100,000. […] In Poland, IVA was included in the NBS program in 2014. Our centre has years of experience in the assessment and treatment of IVA patients. Within this paper we aim to analyze the long-term outcome of Polish IVA patients. […] 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. […] Given the genotype-phenotype correlation, 89 pathogenic variants in the IVD gene have been reported so far (HGMD Professional; updated on 4 December 2019). The relationship regarding IVA manifestation is, however, lacking, and the distribution of hotspot varies among populations.

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

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

  Isovaleric Acidaemia is a very rare disorder. The amount of cases is difficult to estimate because some people with the disorder do not have any symptoms. It is estimated to affect 1-9 in every 100,000 people. In the USA, at least 1 in 250,000 people have the disorder. […] There are currently no figures for the prevalence of Isovaleric Acidaemia in the UK.

• #19 Aspects of Newborn Screening in Isovaleric Acidemia

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

  Using a data set of 1.6 million newborns from Germany, the birth prevalence of IVA was calculated to be 1 in 67,000. […] Prevalences from other countries were reported to be lower, such as 1 in 660,000 in Taiwan or 1 in 105,000 in Portugal. […] An analysis of available evidence by Dionisi-Vici et al. showed a more than four times higher incidence of IVA in the screened population as compared to clinical diagnosis, suggesting that the phenotypic spectrum of IVA detected by NBS is different and may include individuals that would not have presented clinically. […] With NBS becoming an important part of pediatric preventive strategies worldwide, several diagnostic pitfalls have come to attention. […] The possibility of pre-symptomatic diagnosis through NBS and the apparent benefit that has been demonstrated for patients diagnosed and treated early make IVA an ideal candidate for NBS programs.

• #20 Aspects of Newborn Screening in Isovaleric Acidemia

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

  An additional “mild” form of IVA with only slight biochemical abnormalities and a potentially asymptomatic phenotype has been discovered by NBS. […] Overall, longitudinal studies of screened individuals with IVA are needed to allow for a better understanding of the long-term outcome and clinical spectrum including the “mild” phenotype and to provide the basis for management recommendations and counseling.

• #21 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 inclusion of IVA in NBS programs in many countries has broadened knowledge of the variability of the condition, whereas prior to NBS, two distinct clinical phenotypes were known, an “acute neonatal” and a “chronic intermittent” form. […] The first countries that introduced IVA to their NBS programs were Australia, where IVA was included in the New South Wales NBS program in 1998, and Germany, where it was first included in the Bavarian NBS program in 1999. […] Since then, it has been implemented in national NBS programs in about 30 countries worldwide, and most recently (2015), in England and Wales.

• #22 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 inclusion of IVA in NBS programs in many countries has broadened knowledge of the variability of the condition, whereas prior to NBS, two distinct clinical phenotypes were known, an “acute neonatal” and a “chronic intermittent” form. […] The first countries that introduced IVA to their NBS programs were Australia, where IVA was included in the New South Wales NBS program in 1998, and Germany, where it was first included in the Bavarian NBS program in 1999. […] Since then, it has been implemented in national NBS programs in about 30 countries worldwide, and most recently (2015), in England and Wales.

• #23 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 inclusion of IVA in NBS programs in many countries has broadened knowledge of the variability of the condition, whereas prior to NBS, two distinct clinical phenotypes were known, an “acute neonatal” and a “chronic intermittent” form. […] The first countries that introduced IVA to their NBS programs were Australia, where IVA was included in the New South Wales NBS program in 1998, and Germany, where it was first included in the Bavarian NBS program in 1999. […] Since then, it has been implemented in national NBS programs in about 30 countries worldwide, and most recently (2015), in England and Wales.

• #24 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) is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD), which catalyses the oxidation of isovaleryl-CoA to 3-methylcrotonyl-CoA during the third step of leucine catabolism. 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. IVA can be categorized into three subtypes: (1) Acute neonatal type: disease presents in the first 2 weeks after birth, including severe metabolic acidosis and encephalopathy, often accompanied by leukopenia, neutropenia, thrombocytopenia, electrolyte disturbances, and hypo- or hyperglycaemia. The patient may experience coma or death if not properly treated. (2) Chronic intermittent type: findings include psychomotor delay and paroxysmal metabolic disorder. During the metabolic crisis, clinical manifestations are similar to those of the acute neonatal type. (3) Asymptomatic type: findings include mild biochemical abnormalities.

• #25 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) is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD), which catalyses the oxidation of isovaleryl-CoA to 3-methylcrotonyl-CoA during the third step of leucine catabolism. 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. IVA can be categorized into three subtypes: (1) Acute neonatal type: disease presents in the first 2 weeks after birth, including severe metabolic acidosis and encephalopathy, often accompanied by leukopenia, neutropenia, thrombocytopenia, electrolyte disturbances, and hypo- or hyperglycaemia. The patient may experience coma or death if not properly treated. (2) Chronic intermittent type: findings include psychomotor delay and paroxysmal metabolic disorder. During the metabolic crisis, clinical manifestations are similar to those of the acute neonatal type. (3) Asymptomatic type: findings include mild biochemical abnormalities.

• #26 Aspects of Newborn Screening in Isovaleric Acidemia

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

  An additional “mild” form of IVA with only slight biochemical abnormalities and a potentially asymptomatic phenotype has been discovered by NBS. […] Overall, longitudinal studies of screened individuals with IVA are needed to allow for a better understanding of the long-term outcome and clinical spectrum including the “mild” phenotype and to provide the basis for management recommendations and counseling.

• #27 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) is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD), which catalyses the oxidation of isovaleryl-CoA to 3-methylcrotonyl-CoA during the third step of leucine catabolism. 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. IVA can be categorized into three subtypes: (1) Acute neonatal type: disease presents in the first 2 weeks after birth, including severe metabolic acidosis and encephalopathy, often accompanied by leukopenia, neutropenia, thrombocytopenia, electrolyte disturbances, and hypo- or hyperglycaemia. The patient may experience coma or death if not properly treated. (2) Chronic intermittent type: findings include psychomotor delay and paroxysmal metabolic disorder. During the metabolic crisis, clinical manifestations are similar to those of the acute neonatal type. (3) Asymptomatic type: findings include mild biochemical abnormalities.

• #28 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

  We searched for reported cases in the PubMed database and the Wanfang database of China using the term „isovaleric acidaemia”. A total of 154 cases from 25 relevant references were combined with the present case, resulting in a sample of 155 patients, comprising 52 asymptomatic individuals and 103 symptomatic individuals (including 64 with neonatal onset, and 39 with chronic intermittent disease) with onset from ages from 1 month to 10 years (median age, 2 years). […] Currently, there are no data on the overall prevalence of IVA in China. The prevalence of neonatal IVA is 1:400,000 in the neonatal screening data of the Shanghai Institute of Pediatrics. The overall prevalence of IVA is 1:365,000 in Taiwan, 1:250,000 in the United States, and 1–9/100,000 in other Western countries.

• #29 Isovaleric acidemia | Newborn Screening

  https://newbornscreening.hrsa.gov/conditions/isovaleric-acidemia

  It is estimated that fewer than 20 babies are born with this condition each year in the United States. […] Newborn screening for isovaleric acidemia is done using a small amount of blood collected from your baby’s heel. […] False-positive newborn screening results for this condition are rare.

• #30 Isovaleric acidaemia – Genomics Education Programme

  http://www.genomicseducation.hee.nhs.uk/documents/isovaleric-acidaemia/

  The prevalence of the condition is approximately 1 in 155,000, based on EU data. […] As part of the NHS newborn blood spot screening (NBS) programme in England, C5 aclycarnitine in dried blood spots is used as the initial diagnostic metabolite. […] Families should be referred for genetic counselling; this is particularly important in families where consanguineous marriage is customary as there may be implications for the wider family.

• #31 Isovaleric acidemia | Newborn Screening

  https://newbornscreening.hrsa.gov/conditions/isovaleric-acidemia

  It is estimated that fewer than 20 babies are born with this condition each year in the United States. […] Newborn screening for isovaleric acidemia is done using a small amount of blood collected from your baby’s heel. […] False-positive newborn screening results for this condition are rare.

• #32 Isovaleric Acidemia (IVA) | New York State Department of Health, Wadsworth Center

  https://www.wadsworth.org/public-health-programs/newborn-screening/newborn-screening-program/isovaleric-acidemia-iva

  Incidence: The incidence of IVA is estimated to be 1 in 250,000. […] Newborn screening cannot distinguish between IVA and 2-Methylbutyrylglycinuria (2-MBCD). […] Patients with an abnormal newborn screen for IVA are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of IVA.

• #33 Isovaleric Acidemia (IVA) | Revvity

  https://www.revvity.com/disorders/isovaleric-acidemia-iva

  Isovaleric acidemia results from a defect in the metabolism of the amino acid, leucine. […] IVA is estimated to occur in less than 1 in 100,000 live births. […] Newborns can be screened for IVA using tandem mass spectrometry analysis of a heel-stick dried blood spot specimen. […] Prenatal diagnosis is possible by measuring isovalerylglycine in amniotic fluid and by measuring isovaleryl-CoA dehydrogenase enzyme activity in chorionic villus specimens or cultured amniocytes.

• #34 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. […] Isovaleric acidemia is caused by a deficiency of the mitochondrial enzyme isovaleryl-CoA dehydrogenase. […] The abnormal accumulation of isovalerylglycine is diagnostic. […] Most patients develop vomiting, acidosis, lethargy, and coma in the newborn period. […] Isovaleric acidemia responds well to treatment with supplemental glycine (250 mg/kg) which binds with the isovaleric acid and is excreted as isovalerylglycine. […] Isovaleric acidemia is an autosomal recessive disease caused by deficiency of the mitochondrial enzyme isovaleryl-CoA dehydrogenase. […] Prenatal diagnosis has also been made by the incorporation of labeled isovaleric acid in chorionic villus material. […] Isovalerylglycine appears to be the metabolite of choice; it has been diagnostic as early as 12 weeks of gestation. […] The majority of OAs causing hyperammonemia results from a defect in the branched-chain amino acids (BCAAs) catabolism. […] The most important are propionic acidemia, methylmalonic acidemia, and isovaleric acidemia.

• #35

  https://omim.org/entry/243500

  A number sign (#) is used with this entry because of evidence that isovaleric acidemia (IVA) is caused by homozygous or compound heterozygous mutation in the isovaleryl CoA dehydrogenase gene (IVD; 607036) on chromosome 15q15. […] Isovaleric acidemia (IVA) is an inborn error of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase. […] Vockley et al. (1991) demonstrated with autosomal recessive inheritance of isovaleric acidemia. […] Since the implementation of newborn screening by tandem mass spectrometry in many states and countries, presymptomatic diagnosis of isovaleric acidemia has been possible.

• #36

  https://omim.org/entry/243500

  A number sign (#) is used with this entry because of evidence that isovaleric acidemia (IVA) is caused by homozygous or compound heterozygous mutation in the isovaleryl CoA dehydrogenase gene (IVD; 607036) on chromosome 15q15. […] Isovaleric acidemia (IVA) is an inborn error of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase. […] Vockley et al. (1991) demonstrated with autosomal recessive inheritance of isovaleric acidemia. […] Since the implementation of newborn screening by tandem mass spectrometry in many states and countries, presymptomatic diagnosis of isovaleric acidemia has been possible.

• #37 Isovaleric acidemia (IVA) | European registry and network for Intoxication type Metabolic Diseases – E-IMD

  https://www.e-imd.org/diseases/organic-acidurias-oads/isovaleric-acidemia-iva

  The incidence of IVA has a range from 1/62,500 live births in parts of Germany to 1/250,000 in the United States. […] With the advent of the use of MS/MS to screen newborn blood spots for acylcarnitine concentrations, many patients with IVA have been identified as newborns prior to the development of symptoms. […] Nearly half of the mutant IVD alleles sequenced from infants diagnosed by newborn screening have been found to contain a common recurring missense mutation (932CT; A282V). […] Newborn screening patients who carry this common mutation either in a homozygous or compound heterozygous state and their sibs skew the spectrum of IVA. So more than half of IVA patients represent a new mild phenotype and potentially remain asymptomatic. This is an expansion of our view of the natural history of IVA prior to the newborn screening era and leads to significant implications for management and genetic counseling.

• #38 Isovaleric acidemia (IVA) | European registry and network for Intoxication type Metabolic Diseases – E-IMD

  https://www.e-imd.org/diseases/organic-acidurias-oads/isovaleric-acidemia-iva

  The incidence of IVA has a range from 1/62,500 live births in parts of Germany to 1/250,000 in the United States. […] With the advent of the use of MS/MS to screen newborn blood spots for acylcarnitine concentrations, many patients with IVA have been identified as newborns prior to the development of symptoms. […] Nearly half of the mutant IVD alleles sequenced from infants diagnosed by newborn screening have been found to contain a common recurring missense mutation (932CT; A282V). […] Newborn screening patients who carry this common mutation either in a homozygous or compound heterozygous state and their sibs skew the spectrum of IVA. So more than half of IVA patients represent a new mild phenotype and potentially remain asymptomatic. This is an expansion of our view of the natural history of IVA prior to the newborn screening era and leads to significant implications for management and genetic counseling.

• #39 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

  Isovaleric acidemia (IVA, OMIM: 243500) is an autosomal recessive leucine inborn error of metabolism caused by the deficiency of mitochondrial isovaleryl-CoA dehydrogenase (IVD; EC 1.2.99.10), encoded by the IVD gene. It is one of the four “classical” organic acidemias: propionic (PA), methylmalonic (MMA), glutaric (GA), and IVA, with a prevalence 1–9/100,000. […] In Poland, IVA was included in the NBS program in 2014. Our centre has years of experience in the assessment and treatment of IVA patients. Within this paper we aim to analyze the long-term outcome of Polish IVA patients. […] 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. […] Given the genotype-phenotype correlation, 89 pathogenic variants in the IVD gene have been reported so far (HGMD Professional; updated on 4 December 2019). The relationship regarding IVA manifestation is, however, lacking, and the distribution of hotspot varies among populations.

• #40 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

  Isovaleric acidemia (IVA, OMIM: 243500) is an autosomal recessive leucine inborn error of metabolism caused by the deficiency of mitochondrial isovaleryl-CoA dehydrogenase (IVD; EC 1.2.99.10), encoded by the IVD gene. It is one of the four “classical” organic acidemias: propionic (PA), methylmalonic (MMA), glutaric (GA), and IVA, with a prevalence 1–9/100,000. […] In Poland, IVA was included in the NBS program in 2014. Our centre has years of experience in the assessment and treatment of IVA patients. Within this paper we aim to analyze the long-term outcome of Polish IVA patients. […] 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. […] Given the genotype-phenotype correlation, 89 pathogenic variants in the IVD gene have been reported so far (HGMD Professional; updated on 4 December 2019). The relationship regarding IVA manifestation is, however, lacking, and the distribution of hotspot varies among populations.

• #41 Orphanet: Isovaleric acidemia

  https://www.orpha.net/en/disease/detail/33

  A rare, autosomal recessive, organic aciduria that is characterized by variable clinical presentation ranging from acute neonatal onset of metabolic decompensation to later onset of chronic, non-specific manifestations including failure to thrive and/or developmental delay. All patients are prone to intermittent, acute metabolic decompensation. During metabolic episodes, urine analysis demonstrates elevated isovaleric acid derivatives. […] Accurate data on the prevalence is not readily available. Best estimates come from newborn screening studies that estimate prevalence at birth between 1/50,000-150,000. […] 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.

• #42 Orphanet: Isovaleric acidemia

  https://www.orpha.net/en/disease/detail/33

  A rare, autosomal recessive, organic aciduria that is characterized by variable clinical presentation ranging from acute neonatal onset of metabolic decompensation to later onset of chronic, non-specific manifestations including failure to thrive and/or developmental delay. All patients are prone to intermittent, acute metabolic decompensation. During metabolic episodes, urine analysis demonstrates elevated isovaleric acid derivatives. […] Accurate data on the prevalence is not readily available. Best estimates come from newborn screening studies that estimate prevalence at birth between 1/50,000-150,000. […] 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.

• #43 Isovaleric Acidemia (IVA) | Newborn Screening Ontario

  https://www.newbornscreening.on.ca/en/results/screen-positive-results/disease-information/isovaleric-acidemia-iva/

  Approximate incidence in Ontario: 1 in 100,000 to 200,000. […] Screening is important. […] In Ontario, a heel prick is used to take a few drops of blood from each baby shortly after birth. […] Babies identified at a young age through screening can be treated early to help prevent health problems. […] Follow up testing is important to find out whether the baby truly has IVA. […] Follow up testing is arranged as soon as possible and involves blood and urine tests. […] Screening and treatment aim to prevent metabolic crises and help children with IVA live healthier lives. […] Screening and early treatment also help to prevent the symptoms of IVA. […] Treatment for IVA is started as early as possible and is usually life long. […] A team, including a metabolic doctor and a dietitian, cares for babies with IVA. […] Early treatment often allows babies with IVA to lead healthy lives with normal growth and intelligence.

• #44 Orphanet: Isovaleric acidemia

  https://www.orpha.net/en/disease/detail/33

  A rare, autosomal recessive, organic aciduria that is characterized by variable clinical presentation ranging from acute neonatal onset of metabolic decompensation to later onset of chronic, non-specific manifestations including failure to thrive and/or developmental delay. All patients are prone to intermittent, acute metabolic decompensation. During metabolic episodes, urine analysis demonstrates elevated isovaleric acid derivatives. […] Accurate data on the prevalence is not readily available. Best estimates come from newborn screening studies that estimate prevalence at birth between 1/50,000-150,000. […] 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.

• #45 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

  Isovaleric acidemia (IVA, OMIM: 243500) is an autosomal recessive leucine inborn error of metabolism caused by the deficiency of mitochondrial isovaleryl-CoA dehydrogenase (IVD; EC 1.2.99.10), encoded by the IVD gene. It is one of the four “classical” organic acidemias: propionic (PA), methylmalonic (MMA), glutaric (GA), and IVA, with a prevalence 1–9/100,000. […] In Poland, IVA was included in the NBS program in 2014. Our centre has years of experience in the assessment and treatment of IVA patients. Within this paper we aim to analyze the long-term outcome of Polish IVA patients. […] 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. […] Given the genotype-phenotype correlation, 89 pathogenic variants in the IVD gene have been reported so far (HGMD Professional; updated on 4 December 2019). The relationship regarding IVA manifestation is, however, lacking, and the distribution of hotspot varies among populations.

• #46 Isovaleric Acidemia Market Size & Share 2034

  https://www.imarcgroup.com/isovaleric-acidemia-market

  The isovaleric acidemia market has been comprehensively analyzed in IMARC’s new report titled „Isovaleric Acidemia Market: Epidemiology, Industry Trends, Share, Size, Growth, Opportunity, and Forecast 2024-2034”. […] The increasing cases of genetic mutations, leading to the deficiency of the isovaleryl-CoA dehydrogenase enzyme are primarily driving the isovaleric acidemia market. […] Moreover, the widespread adoption of newborn screening programs, enabling early detection and intervention, is further bolstering the market growth. […] IMARC Group’s new report provides an exhaustive analysis of the isovaleric acidemia market in the United States, EU5 (Germany, Spain, Italy, France, and United Kingdom) and Japan. […] According to the report the United States has the largest patient pool for isovaleric acidemia and also represents the largest market for its treatment.

• #47 Isovaleric Acidemia – Market Insight, Epidemiology, and Market Forecast – 2034

  https://www.giiresearch.com/report/del1507017-isovaleric-acidemia-market-insight-epidemiology.html

  The Isovaleric Acidemia epidemiology division provide insights about historical and current Isovaleric Acidemia patient pool and forecasted trend for every seven major countries. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. This part of the DelveInsight report also provides the diagnosed patient pool and their trends along with assumptions undertaken. […] The disease epidemiology covered in the report provides historical as well as forecasted Isovaleric Acidemia epidemiology scenario in the 7MM covering the United States, EU5 countries (Germany, Spain, Italy, France, and the United Kingdom), and Japan from 2020 to 2034. […] The epidemiology segment also provides the Isovaleric Acidemia epidemiology data and findings across the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan.

• #48 Isovaleric Acidemia Market Size & Share 2034

  https://www.imarcgroup.com/isovaleric-acidemia-market

  The isovaleric acidemia market has been comprehensively analyzed in IMARC’s new report titled „Isovaleric Acidemia Market: Epidemiology, Industry Trends, Share, Size, Growth, Opportunity, and Forecast 2024-2034”. […] The increasing cases of genetic mutations, leading to the deficiency of the isovaleryl-CoA dehydrogenase enzyme are primarily driving the isovaleric acidemia market. […] Moreover, the widespread adoption of newborn screening programs, enabling early detection and intervention, is further bolstering the market growth. […] IMARC Group’s new report provides an exhaustive analysis of the isovaleric acidemia market in the United States, EU5 (Germany, Spain, Italy, France, and United Kingdom) and Japan. […] According to the report the United States has the largest patient pool for isovaleric acidemia and also represents the largest market for its treatment.

• #49 Isovaleric Acidemia – Market Insight, Epidemiology, and Market Forecast – 2034

  https://www.giiresearch.com/report/del1507017-isovaleric-acidemia-market-insight-epidemiology.html

  The Isovaleric Acidemia epidemiology division provide insights about historical and current Isovaleric Acidemia patient pool and forecasted trend for every seven major countries. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. This part of the DelveInsight report also provides the diagnosed patient pool and their trends along with assumptions undertaken. […] The disease epidemiology covered in the report provides historical as well as forecasted Isovaleric Acidemia epidemiology scenario in the 7MM covering the United States, EU5 countries (Germany, Spain, Italy, France, and the United Kingdom), and Japan from 2020 to 2034. […] The epidemiology segment also provides the Isovaleric Acidemia epidemiology data and findings across the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan.

• #50 Isovaleric Acidemia (IVA) | New York State Department of Health, Wadsworth Center

  https://www.wadsworth.org/public-health-programs/newborn-screening/newborn-screening-program/isovaleric-acidemia-iva

  Incidence: The incidence of IVA is estimated to be 1 in 250,000. […] Newborn screening cannot distinguish between IVA and 2-Methylbutyrylglycinuria (2-MBCD). […] Patients with an abnormal newborn screen for IVA are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of IVA.

• #51 Aspects of Newborn Screening in Isovaleric Acidemia

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

  An additional “mild” form of IVA with only slight biochemical abnormalities and a potentially asymptomatic phenotype has been discovered by NBS. […] Overall, longitudinal studies of screened individuals with IVA are needed to allow for a better understanding of the long-term outcome and clinical spectrum including the “mild” phenotype and to provide the basis for management recommendations and counseling.

• #52 Two Siblings Born With Isovaleric Acidemia: One Caught by Newborn Screening, One Wasn’t – APHL Blog

  https://www.aphlblog.org/two-siblings-born-with-isovaleric-acidemia-one-caught-with-newborn-screening-one-wasnt/

  With spring in the air, the temperatures are climbing, the famous cherry blossoms have reached peak bloom and once again, the baseball and softball fields have come alive in Northern Virginia. For a child like Caroline, living with a life threatening inborn error of metabolism called isovaleric acidemia (IVA), it is a gift. Early detection of her disorder by newborn screening has enabled Caroline to have appropriate life-long medical intervention and management of her disorder, so that she has the strength and good health to play ball…something we never take for granted. […] He too has IVA, but due to a twist of fate, the disorder was not detected when he was a newborn as a result of lack of comprehensive newborn screening at the time he was born. […] The diagnosis of isovaleric academia came too late to prevent severe brain damage.

• #53 Two Siblings Born With Isovaleric Acidemia: One Caught by Newborn Screening, One Wasn’t – APHL Blog

  https://www.aphlblog.org/two-siblings-born-with-isovaleric-acidemia-one-caught-with-newborn-screening-one-wasnt/

  However, it inspired me to become an advocate for expanded newborn screening at the state and national level to help prevent other babies and children from sharing Stephen’s fate. […] Together, Stephen and Caroline are a clear representation of the importance of newborn screening and the dramatic consequence with and without…a forever reminder every baseball/softball season.

• #54 Two Siblings Born With Isovaleric Acidemia: One Caught by Newborn Screening, One Wasn’t – APHL Blog

  https://www.aphlblog.org/two-siblings-born-with-isovaleric-acidemia-one-caught-with-newborn-screening-one-wasnt/

  With spring in the air, the temperatures are climbing, the famous cherry blossoms have reached peak bloom and once again, the baseball and softball fields have come alive in Northern Virginia. For a child like Caroline, living with a life threatening inborn error of metabolism called isovaleric acidemia (IVA), it is a gift. Early detection of her disorder by newborn screening has enabled Caroline to have appropriate life-long medical intervention and management of her disorder, so that she has the strength and good health to play ball…something we never take for granted. […] He too has IVA, but due to a twist of fate, the disorder was not detected when he was a newborn as a result of lack of comprehensive newborn screening at the time he was born. […] The diagnosis of isovaleric academia came too late to prevent severe brain damage.

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

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

  An early diagnosis leads to early treatment and subsequently results in normal development of the children. […] The case of IVA reported herein showed that the mutations were not polymorphic. The frequency of occurrence in the population is extremely low. The clinical and genetic features of this patient help to further expand our knowledge of IVA. Moreover, most cases occur during the neonatal period, and the mortality rate is high. Thus, clinicians should be aware of this disease. Early diagnosis as well as the detection of genetic metabolic diseases may improve patient outcomes.

• #56 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 incidence in China is about 1 in 190000 diagnosed by neonatal MS/MS. […] 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. […] The clinical manifestations vary, and disease onset can range from the neonatal period to the adult period. […] Early diagnosis and treatment are necessary to prevent neonatal mortality and improve the neurologic and cognitive outcomes.

• #57 Isovaleric Acidemia (IVA) | Newborn Screening Ontario

  https://www.newbornscreening.on.ca/en/results/screen-positive-results/disease-information/isovaleric-acidemia-iva/

  Approximate incidence in Ontario: 1 in 100,000 to 200,000. […] Screening is important. […] In Ontario, a heel prick is used to take a few drops of blood from each baby shortly after birth. […] Babies identified at a young age through screening can be treated early to help prevent health problems. […] Follow up testing is important to find out whether the baby truly has IVA. […] Follow up testing is arranged as soon as possible and involves blood and urine tests. […] Screening and treatment aim to prevent metabolic crises and help children with IVA live healthier lives. […] Screening and early treatment also help to prevent the symptoms of IVA. […] Treatment for IVA is started as early as possible and is usually life long. […] A team, including a metabolic doctor and a dietitian, cares for babies with IVA. […] Early treatment often allows babies with IVA to lead healthy lives with normal growth and intelligence.

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