Hypoglycemia Events in Twin Sisters

Case report: We report 2 dizygote twin sisters, from non consanguineous Ashkenazi parents, born at week 36+5, after a non complicated pregnancy.

There were no perinatal concerns, NBS was normal for both. Development and health are normal.

One of the two sisters presented one episode of hypoglycemia with DEX 13 at the age of 8 month after a night of fever and vomiting during intercurrent viral illness.

The second sister presented 2 post nocturnal episodes of hypoglycemia with DEX 35, one at the age of 8 month and the other at the age of 1y 9 mo without intercurrent viral illness. She only showed some palor and weakness at the Emergency Room.

Because the mother was pregnant for about 5 months, they decided to show up for some metabolic and genetic advice.

Metabolic and genetic work up revealed an heterozygotic HMGCS2 variants: Exon 2, c.412T>C and Exon 3, c.586G>C

Mitochondrial 3-Hydroxy-3-Methylglutaryl-CoA synthase deficiency:

HMGCS2 encodes for the mitochondrial enzyme 3 -hydroxy -3 methylglutaryl-CoA synthase 2, that catalyzes the rate limiting reaction of ketogenesis in the mitochondrial matrix

HMG-CoA Synthase deficiency is a rare autosomal recessive disorder that present usually in the first year of life and is characterized by hypoketotic hypoglycemia, vomiting, lethargy and hepatomegaly +\- acidosis after periods of prolonged fasting or illness.

Conclusion:

HMG-CoA synthase deficiency is a rare condition with non specific symptoms that is believed to be underdiagnosed, but with the advent of whole exome\genome sequencing, the incidence of this disorder may become better understood.