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3‐Hydroxyisobutyrate dehydrogenase ( HIBADH ) deficiency—A novel disorder of valine metabolism
Author(s) -
Meyer Melanie,
Hollenbeck Jana C.,
Reunert Janine,
Seelhöfer Anja,
Rust Stephan,
Fobker Manfred,
Biskup Saskia,
Och Ulrike,
Linden Mechthild,
Sass Jörn Oliver,
Marquardt Thorsten
Publication year - 2021
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1002/jimd.12410
Subject(s) - valine , phenotype , dehydrogenase , biology , mutant , urine , nonsense mutation , allele , enzyme , excretion , catabolism , metabolism , amino acid , biochemistry , gene , missense mutation
3‐Hydroxyisobutyric acid (3HiB) is an intermediate in the degradation of the branched‐chain amino acid valine. Disorders in valine degradation can lead to 3HiB accumulation and its excretion in the urine. This article describes the first two patients with a new metabolic disorder, 3‐hydroxyisobutyrate dehydrogenase (HIBADH) deficiency, its phenotype and its treatment with a low‐valine diet. The detected mutation in the HIBADH gene leads to nonsense‐mediated mRNA decay of the mutant allele and to a complete loss‐of‐function of the enzyme. Under strict adherence to a low‐valine diet a rapid decrease of 3HiB excretion in the urine was observed. Due to limited patient numbers and intrafamilial differences in phenotype with one affected and one unaffected individual, the clinical phenotype of HIBADH deficiency needs further evaluation.