AUH

AUH Full Name

AU RNA binding protein/enoyl-CoA hydratase

AUH Introduction

AUH (AU RNA binding protein/enoyl-CoA hydratase), also known as 3-methylglutaconyl-CoA hydratase, is a mitochondrial enzyme encoded by the AUH gene that plays an essential role in the degradation of the branched-chain amino acid leucine. The protein functions as an enoyl-CoA hydratase involved in the conversion of 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA, a key step in the leucine catabolic pathway. Beyond its metabolic enzyme activity, AUH has also been characterized as an RNA-binding protein, reflecting its potential involvement in mitochondrial RNA-related regulation. When AUH function is impaired, the mitochondrial leucine degradation pathway becomes disrupted, leading to accumulation of toxic organic acid intermediates and abnormal metabolic profiles that can be detected through biochemical screening.

The most recognized disease association of AUH deficiency is 3-methylglutaconic aciduria type I, a rare inherited metabolic disorder caused by biallelic pathogenic variants in the AUH gene. Patients with AUH defects typically exhibit elevated urinary 3-methylglutaconic acid, 3-methylglutaric acid, and sometimes 3-hydroxyisovaleric acid, reflecting impaired leucine metabolism. Recent studies have highlighted that the clinical presentation of MGCA1 can be highly variable, ranging from asymptomatic individuals identified through newborn screening to patients with developmental delay, particularly speech impairment. Early diagnosis remains challenging because conventional metabolic testing may not always provide definitive results, and some patients require advanced approaches such as enzyme activity assays, next-generation sequencing, or genomic structural variant analysis to confirm AUH-related disease.

Understanding AUH biology is increasingly important for researchers investigating mitochondrial metabolism, inherited metabolic disorders, and precision diagnostics. Although MGCA1 is considered an ultra-rare disorder, emerging evidence suggests that its clinical spectrum may be broader than previously recognized, and detection bias may have contributed to underestimation of disease prevalence. Studies of AUH deficiency also provide valuable insights into how mitochondrial metabolic dysfunction can influence systemic physiology and neurological development. For scientists exploring metabolic disease mechanisms, biomarker discovery, or therapeutic strategies targeting mitochondrial pathways, AUH represents an important molecular target linking amino acid metabolism, mitochondrial function, and human genetic disease.

Alternate Names for AUH

AUH; AU RNA binding protein/enoyl-CoA hydratase; methylglutaconyl-CoA hydratase, mitochondrial; 3-methylglutaconyl-CoA hydratase; AU-binding protein/Enoyl-CoA hydratase; AU-specific RNA-binding enoyl-CoA hydratase; AU RNA binding protein/enoyl-Coenzyme A hydratase; AU RNA-binding protein/enoyl-Coenzyme A hydratase

• 1.Nardecchia F, et al.; 3-Methylglutaconic Aciduria Type I Due to AUH Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature. Int J Mol Sci. 2022, 23(8):4422.
  2.Itonaga T, et al.; Asymptomatic 3-methylglutaconic aciduria type 1 detected by high C5-OH on newborn screening. Mol Genet Metab Rep. 2023, 38:101024..