Introduction: Hydroxymethylglutaric aciduria is a rare metabolic disease that is caused by the deficiency of the enzyme 3-hydroxy-3-methylglutaryl-CoA lyase, which participates in the metabolism of leucine and in the formation of ketone bodies. The symptomatology usually occurs in the first two years of life and consists of nausea, vomiting, diarrhea, hypotoniaanddepressed level of consciousness. Metabolic acidosis occurs during crises as a result of the accumulation of metabolites and hypoglycaemia.The crises are triggered by infections or prolonged fasting.
Case report: A 18-month-old female who comes to the hospital due to seizures andhypotonia, with the suspicion of encephalitis. The blood test shows hypoglycaemia (19 mg/dL) and non-ketotic metabolic acidosis with high anion GAP. A study of hypoglycaemia in children is performed with the following results: marked increase of the excretion of leucine metabolites, decreased levels of free carnitine and normal levels of total and esterified carnitine. The diagnostic suspicion is Hydroxymethylglutaric aciduria, which is confirmed by a skin biopsy. Treatment is started with a diet low in proteins of high biological value, carnitine, and a leucine-free nutritional supplement. We also indicate to avoid prolonged fasting. With the adjustments, the patient showed a good evolution having only one admission due to a hypoglycaemia associated with a rotavirus gastroenteritis. In the follow-upthe genetic testindicates alikely pathogenic variant in apparent homozygotes: c.575T>C (p.Phe192Ser) in the HMGCL gene. At the age of 21, the patient debuted with diabetes with associated cardinal symptoms, which led to the initiation of insulin in basal-bolus therapy. Blood test results: GAD65-Ab >250 IU/mL, C-peptide 0.54 ng/mL and negative anti-IA2 and anti-Insulin antibodies. Currently the patient has good metabolic control with glycosylated hemoglobin of 6.1%.
Conclusions: We present a patient with type 1 DM who cannot present with metabolic ketoacidosis due to the deficit of the HMGCL enzyme. The association of both diseases is not previously described in the literature. Could an SGLT2i be used safely in this case? Is it beneficial that she cannot have ketoacidosis?
18 - 21 May 2019
European Society of Endocrinology