Hyperinsulinism/hyperammonemia (HI/HA) syndrome due to a mutation in the glutamate dehydrogenase gene / Síndrome de hiperinsulinemia/hiperamonemia devido a uma mutação no gene da glutamato desidrogenase

The hyperinsulinism/hyperammonemia (HI/HA) syndrome is a rare autosomal dominant disease manifested by hypoglycemic symptoms triggered by fasting or high-protein meals, and by elevated serum ammonia. HI/HA is the second most common cause of hyperinsulinemic hypoglycemia of infancy, and it is caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Biochemical evaluation, as well as direct sequencing of exons and exon-intron boundary regions of the GLUD1 gene, were performed in a 6-year old female patient presenting fasting hypoglycemia and hyperammonemia. The patient was found to be heterozygous for one de novo missense mutation (c.1491A>G; p.Il497Met) previously reported in a Japanese patient. Treatment with diazoxide 100 mg/day promoted complete resolution of the hypoglycemic episodes. Arq Bras Endocrinol Metab. 2012;56(8):485-9.

A síndrome de hiperinsulinemia/hiperamonemia (HI/HA) é uma condição rara, de herança autossômica dominante, que se manifesta por sintomas de hipoglicemia desencadeada por jejum ou refeições de alto conteúdo proteico, juntamente com elevação da concentração de amônia sérica. HI/HA é a segunda causa de hipoglicemia hiperinsulinêmica da infância e é causada por mutações ativadoras no GLUD1, o gene que codifica a enzima mitocondrial glutamato desidrogenase (GDH). A avaliação bioquímica, bem como o sequenciamento direto dos éxons e junções éxon-íntron do gene GLUD1, foi realizada em uma paciente de 6 anos de idade com hipoglicemia de jejum e hiperamonemia. A paciente apresentava uma mutação de novo missense (c.1491A>G; p.Il497Met) em heterozigose, que havia sido previamente relatada em um paciente japonês. O tratamento com diazóxido 100 mg/dia promoveu resolução completa dos episódios hipoglicêmicos. Arq Bras Endocrinol Metab. 2012;56(8):485-9.

Studies of the immediate postpartum diabetes remission and/or hypoglycemia after cesarean section in diabetic pregnancy

Five non-diabetic subjects, 5 gestational diabetics (GDM) treated with diet and 4 non-insulin dependent pregestational diabetics (NIDDM) treated with beef-pork insulin during their pregnancy, undergoing elective cesarean section (C-s), were given dextrose infusions without insulin for 7 hours (h) starting lh before the operation. Multiple blood samples were drawn up to 72 h after the C-s. The lowest glucose levels were observed at 3 3 or 6 h after surgery in all but two subjects. Plasma glucose below 2.75 mmol/l (49.5 mg/dl) were observed in 2 NIDDM patients. While in the non-diabetics and GDM the free (total) insulin and C-peptide values fell to very low levels, coinciding with the fall in plasma glucose, in the NIDDM there was a negative correlation between nadir glucose and free insulin levels with the progressive fall of antibody-bound insulin. In 3 out of NIDDM patients the antibodybound insulin fell to 57 to 73 per cent of the preoperative values. IGF-I/SmC, lower in the NIDDM, hGH immunoreactivity and hPL fell after C-s. The results suggest increased glucose utilization insulin-independent in the immediate postpartum in the non-diabetic pregnancy and GDM. However, in the NIDMM, in the presence of significant levels of free insulin, they tend to develop lower plasma glucose levels, sometimes hypoglycemia. Furthermore, lower IGF-I/Smc levels in the NIDDM in comparison to the non-diabetics and GDM would discard their role in the induction of hypoglycemia.