Maternal isovaleric acidemia

Shih, Vivian E.; Aubry, Richard H.; DeGrande, G.; Gursky, S; Tanaka, Kay

doi:10.1016/s0022-3476(84)80367-4

Cited by 33 publications

(21 citation statements)

References 5 publications

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“…However, sparse information on adolescent and adult patients in the literature indicates that even patients who have been metabolically stable for more than one decade are still prone to metabolic decompensation in episodes of catabolic stress [19-21]. Towards adolescence and adulthood, trigger factors may change and comprise general anesthesia, excessive sports and physical exertion, low-calorie diets and fasting, pregnancy, and alcohol potentially resulting in a catabolic state with increased endogenous protein turnover and the risk of potentially life-threatening crises.…”

Section: Discussionmentioning

confidence: 99%

Clinical and neurocognitive outcome in symptomatic isovaleric acidemia

Grünert

Wendel

Lindner

et al. 2012

Orphanet J Rare Dis

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BackgroundDespite 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. We aimed to investigate the phenotypic presentation and factors determining the neurological and neurocognitive outcomes of patients diagnosed with IVA following clinical manifestation.MethodsRetrospective data on 21 children and adults with symptomatic IVA diagnosed from 1976 to 1999 were analyzed for outcome determinants including age at diagnosis and number of catabolic episodes. Sixteen of 21 patients were evaluated cross-sectionally focusing on the neurological and neurocognitive status. Additionally, 155 cases of patients with IVA published in the international literature were reviewed and analyzed for outcome parameters including mortality.Results57% 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. No other organ complications were found. 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.ConclusionsWithin the group of "classical" organic acidurias, IVA appears to be exceptional considering its milder neuropathologic implications. The potential to avoid neonatal mortality and to improve neurologic and cognitive outcome under early treatment reinforces IVA to be qualified for newborn screening.

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Section: Discussionmentioning

confidence: 99%

Clinical and neurocognitive outcome in symptomatic isovaleric acidemia

Grünert

Wendel

Lindner

et al. 2012

Orphanet J Rare Dis

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“…Patients appeared initially well, then developed vomiting and lethargy, progressing to coma. The second group presented with relatively non-specific failure to thrive and/or developmental delay (chronic intermittent presentation) [Berry et al, 1988;Elsas and Naglak, 1988;Levy et al, 1973;Mehta et al, 1996;Shih et al, 1984]. Patients who survived an early acute presentation subsequently were indistinguishable from those with the chronic phenotype, and both groups of patients were prone to intermittent acute episodes of decompensation with minor illnesses [Tanaka, 1990].…”

Section: Disease Spectrummentioning

confidence: 99%

Isovaleric acidemia: New aspects of genetic and phenotypic heterogeneity

Vockley

Ensenauer

2006

American J of Med Genetics Pt C

196

161

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Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism caused by a deficiency of the mitochondrial enzyme isovaleryl-CoA dehydrogenase (IVD) resulting in the accumulation of derivatives of isovaleryl-CoA. It was the first organic acidemia recognized in humans and can cause significant morbidity and mortality. Early diagnosis and treatment with a protein restricted diet and supplementation with carnitine and glycine are effective in promoting normal development in severely affected individuals. Both intra-and inter-familial variability have been recognized. Initially, two phenotypes with either an acute neonatal or a chronic intermittent presentation were described. More recently, a third group of individuals with mild biochemical abnormalities who can be asymptomatic have been identified through newborn screening of blood spots by tandem mass spectrometry. IVD is a flavoenzyme that catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA and transfers electrons to the electron transfer flavoprotein. Human IVD has been purified from tissue and recombinant sources and its biochemical and physical properties have been extensively studied. Molecular analysis of the IVD gene from patients with IVA has allowed characterization of different types of mutations in this gene. One missense mutation, 932C>T (A282V), is particularly common in patients identified through newborn screening with mild metabolite elevations and who have remained asymptomatic to date. This mutation leads to a partially active enzyme with altered catalytic properties; however, its effects on clinical outcome and the necessity of therapy are still unknown. A better understanding of the heterogeneity of this disease and the relevance of genotype/phenotype correlations to clinical management of patients are among the challenges remaining in the study of this disorder in the coming years.

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“…Liver fibrosis [28] and, most recently, optic nerve atrophy [71] have also been associated with IVA. Pregnancies of affected women have been reported as uneventful [77][78][79].…”

Section: Clinical Presentationmentioning

confidence: 99%

Aspects of Newborn Screening in Isovaleric Acidemia

Schlune

Riederer

Mayatepek

et al. 2018

IJNS

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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. An additional biochemically mild and potentially asymptomatic form of IVA and its association with a common missense mutation, c.932C>T (p.A282V), was discovered in subjects identified through NBS. Deficiency of short/branched chain specific acyl-CoA dehydrogenase (2-methylbutyryl-CoA dehydrogenase), a defect of isoleucine degradation whose clinical significance remains unclear, also results in elevated C5-carnitine, and may therefore be detected by NBS for IVA. Treatment strategies for the long-term management of symptomatic IVA comprise the prevention of catabolism, dietary restriction of natural protein or leucine intake, and supplementation with L-carnitine and/or L-glycine. Recommendations on how to counsel and manage individuals with the mild phenotype detected by NBS are required.

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Maternal isovaleric acidemia

Cited by 33 publications

References 5 publications

Clinical and neurocognitive outcome in symptomatic isovaleric acidemia

Clinical and neurocognitive outcome in symptomatic isovaleric acidemia

Isovaleric acidemia: New aspects of genetic and phenotypic heterogeneity

Aspects of Newborn Screening in Isovaleric Acidemia

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