Deficiency of 3-hydroxy-3-methylglutaryl-CoA mitochondrial (Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthasedeficiency) - Gen HMGCS2.

Deficiency of 3-hydroxy-3-methylglutaryl-CoA is an inherited mitochondrial metabolic disorder caused by a defect in the enzyme that regulates the formation of ketone bodies. Affected individuals exhibit severe hypoglycemia hypoketotic, mild hepatomegaly, fatty liver, and a pattern of urinary organic acids with increasing short chain dicarboxylic acids medium. This disease occurs generally during the first year of life with vomiting, lethargy, hypotonia and sometimes with shortness of breath and coma .

This disease is due to mutations in the gene HMGCS2, located on the short arm of chromosome 1 (1p13-p12). This gene encodes a protein that belongs to the family of HMG-CoAsintasa. It is a mitochondrial enzyme which catalyzes the first reaction in ketogenesis, a metabolic pathway that provides energy from lipid derivatives for various organs during times of deprivation of carbohydrates, such as fasting.

Has been identified in people with deficiencies of 3-hydroxy-3-methylglutaryl-CoA mitochondrial mutation resulting auna substitution-phenylalanine-leucine at codon 174 phe174-to-leu (F174L) in exon 2 of the gene HMGCS2 and a mutation in heterozygous arg424-to-ter (R424X). Mutations result in a nonfunctional and unstable protein.

Tests in IVAMI: in IVAMI perform detection of mutations associated with deficiency of 3-hydroxy-3-methylglutaryl-CoA mitochondrial, by complete PCR amplification of exons HMGCS2 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).