3-Hydroxy-3-Methylglutaryl-Coenzyme a Lyase Deficiency: A Narrative Review

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency is a rare autosomal recessive inborn error of leucine catabolism and ketogenesis. It is characterized by episodes of hypoketotic hypoglycemia, metabolic acidosis, and hyperammonemia, often precipitated by fasting or intercurrent illness. This narrative review summarizes current evidence on the molecular basis, clinical spectrum, diagnostic approach, and management of the disorder, with emphasis on the role of the clinical pharmacist. Literature indexed in PubMed, Scopus, and Google Scholar was reviewed, and the differential diagnosis, newborn screening, and prognosis are also considered. The disorder results from biallelic pathogenic variants in the gene encoding the enzyme, located on chromosome 1p36.11. Most patients present in the first year of life with acute metabolic decompensation. Diagnosis relies on urinary organic acid and plasma acylcarnitine profiles, confirmed by molecular analysis or enzyme assay. Management is based on prevention of fasting, early intravenous glucose during illness, moderate leucine and protein restriction, and carnitine supplementation. Neurological outcome depends largely on the number and severity of hypoglycemic episodes and on the speed of treatment. Evidence is limited to case series and expert consensus. Early recognition and a structured emergency plan substantially reduce morbidity. Multidisciplinary care, including pharmacist-led medication review and caregiver education, is essential, and prospective registries are needed to define optimal long-term management.