The relationship between IVD and isovaleric acidemia (autosomal recessive) was evaluated using the ClinGen Clinical Validity Framework as of April, 2019. Isovaleric acidemia (IVA) is an inborn error of leucine metabolism characterized by an accumulation of isovaleryl-CoA derivatives in cells, blood and urine. Clinical presentation varies widely from acute neonatal to chronic intermittent and can be detected by newborn screening. Variation in IBD were first identified in humans with the disease as early as 1985 (Ikeda et al., PMID 3863140). To date, over 50 unique variants (missense, nonsense, frameshift, splicing) have been reported (Sakamoto et al., 2015; PMID 26018748). This gene-disease relationship is supported by biochemical assays, in vitro assays, and a mouse model. In summary, IVD is definitively associated with autosomal recessive isovaleric acedmia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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