HMG CoA lyase deficiency: identification of five causal point mutations in codons 41 and 42, including a frequent Saudi Arabian mutation, R41Q

Hereditary deficiency of 3-hydroxy-3-methylglutaryl (HMG) CoA lyase (HL) brings with it episodes of hypoketotic hypoglycemia and coma. It shows up frequently and is clinically severe in Saudi Arabia. In nine Saudi HL-deficient probands genetic diversity was found. Six were homozygous for the missense mutation R41Q. Two were homozygous for the frameshift mutation F305fs(-2). In 32 probands that were non-Saudi and HL-deficient, three R41Q alleles were found. There are four other point damaging mutations in codons 41 and 42, which are important for normal HL catalysis. They account for 21 of 82 mutant alleles in the group of HL-deficient probands.