3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: one disease - many faces

BACKGROUND: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL. METHOD: We performed a systematic literature search to identify all published cases. Two hundred eleven patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided. RESULTS: More than 95% of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4% already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6% of patients showing normal development. CONCLUSION: This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.