Abstract：Mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase deficiency (HMCSD) is caused by HMGCS2 gene mutation. This paper reports the clinical and genetic features of an infant with this disease. The 8-month-old female infant was admitted to the hospital with diarrhea for 1 week and fever and convulsion for 1 day. The child presented with seizures, acidosis, hypoglycemia, abnormal liver function, myocardial injury and coagulation dysfunction. The new homozygous mutation c.1502G > A(p.R501Q) in the HMGCS2 gene was found in the infant by genetic testing. The mutant gene was found to be harmful by bioinformatics software analysis. Urine organic acid analysis indicated that 4-hydroxy-6-methyl-2-pyranone was significantly increased, which was consistent with the results of genetic testing. The infant was definitely diagnosed with HMCSD.
Wolf NI, Rahman S, Clayton PT, et al. Mitochondrial HMGCoA synthase deficiency:identification of two further patients carrying two novel mutations[J]. Eur J Pediatr, 2003, 162(4):279-280.
[2]
Aledo R, Zschocke J, Pié J, et al. Genetic basis of mitochondrial HMG-CoA synthase deficiency[J]. Hum Genet, 2001, 109(1):19-23.
[3]
Ramos M, Menao S, Arnedo M, et al. New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations[J]. Eur J Med Genet, 2013, 56(8):411-415.
Rescigno T, Capasso A, Tecce MF, et al. Involvement of nutrients and nutritional mediators in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene expression[J]. J Cell Physiol, 2018, 233(4):3306-3314.
[6]
Puisac B, Ramos M, Arnedo M, et al. Characterization of splice variants of the genes encoding human mitochondrial HMGCoA lyase and HMG-CoA synthase, the main enzymes of the ketogenesis pathway[J]. Mol Biol Rep, 2012, 39(4):4777-4785.
[7]
Shafqat N, Turnbull A, Zschocke J, et al. Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design[J]. J Mol Biol, 2010, 398(4):497-506.
[8]
Fukao T, Mitchell G, Sass JO, et al. Ketone body metabolism and its defects[J]. J Inherit Metab Dis, 2014, 37(4):541-551.
[9]
Thompson GN, Hsu BY, Pitt JJ, et al. Fasting hypoketotic coma in a childwith deficiency of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase[J]. N Engl J Med, 1997, 337:1203-1207.
[10]
Bouchard L, Robert MF, Vinarov D, et al. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency:clinical course and description of causal mutations in two patients[J]. Pediatr Res, 2001, 49(3):326-331.
[11]
Puisac B, Marcos-Alcalde I, Hernández-Marcos M, et al. Human mitochondrial HMG-CoA synthase deficiency:role of enzyme dimerization surface and characterization of three new patients[J]. Int J Mol Sci, 2018, 19(4). pii:E1010. doi:10.3390/ijms19041010.
[12]
Pitt JJ, Peters H, Boneh A, et al. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency:urinary organic acid profiles and expanded spectrum of mutations[J]. J Inherit Metab Dis, 2015, 38(3):459-466.
[13]
Conboy E, Vairo F, Schultz M, et al. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency:Unique presenting laboratory values and a review of biochemical and clinical features[J]. JIMD Rep, 2018, 40:63-69.
[14]
Aledo R, Mir C, Dalton RN, et al. Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency[J]. J Inherit Metab Dis, 2006, 29(1):207-211.
