This study aimed to examine the clinical characteristics of Chinese patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGLD) and identify the prevalent mutations in the HMGCL gene among these patients. The clinical features, biochemical parameters, imaging findings, and genetic variations in 16 previously documented Chinese patients with HMGLD, along with one newly reported case in this study, were comprehensively analyzed. Within the cohort of Chinese patients with HMGLD, 76.5% were diagnosed during infancy, while 35.3% were identified through newborn screening protocols. Acute metabolic disturbances were reported in 88.2% of patients, with neurological manifestations—particularly coma and unconsciousness—presenting as the initial symptoms in 58.9% of cases, and vomiting occurring in 52.9%. Imaging revealed white matter abnormalities in 47.1% of patients and basal ganglia alterations in 17.6%. The homozygous c.122G > A mutation emerged as the predominant genetic variant among Chinese patients with HMGLD, followed by the c.252 + 1G > A mutation. HMGLD is a rare metabolic disorder with significant mortality rates, highlighting the necessity for early diagnosis to prevent metabolic crises. This study is the first to report a case of adolescent-onset HMGLD and characterize the clinical presentation of Chinese patients with the disorder. The study additionally identified a novel homozygous c.133 C > T/p.Gln45Ter mutation in the HMGCL gene.
Yang et al. (Mon,) studied this question.