Department of General Pediatrics, University Hospital, Münster, Germany.
Bonn-Rhein-Sieg University of Applied Sciences, Department of Natural Sciences & Institute for Functional Gene Analytics (IFGA), RG Inborn Errors of Metabolism, Rheinbach, Germany.
J Inherit Metab Dis. 2021 Nov;44(6):1323-1329. doi: 10.1002/jimd.12410. Epub 2021 Jul 5.
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.
3-羟基异丁酸（3HiB）是支链氨基酸缬氨酸降解的中间产物。缬氨酸降解障碍可导致 3HiB 蓄积，并从尿液中排出。本文描述了首例两种新型代谢紊乱，即 3-羟基异丁酰辅酶 A 脱氢酶（HIBADH）缺乏症，及其表型，并对其进行了低缬氨酸饮食治疗。在 HIBADH 基因中检测到的突变导致突变等位基因的无意义介导的 mRNA 降解，并导致酶的完全失活。严格遵循低缬氨酸饮食后，尿液中 3HiB 的排泄迅速减少。由于患者数量有限，以及同一家族中表型存在个体差异，即一个受累和一个未受累个体，HIBADH 缺乏症的临床表型需要进一步评估。
