SUN-LB034 A Rare Cause of Hyperinsulinemic Hypoglycemia in Adulthood: A Case Report and Review of the Literature

Abstract

Introduction: Post-prandial hypoglycaemia (PPH) after consumption of protein is a vanishingly rare condition. Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in infants and children, although it is uncommon to be diagnosed in adulthood. Dominant activation of glutamate dehydrogenase, encoded for by the GLUD1 gene, causes the hyperinsulinemia/hyperammonemia syndrome (HHS). Within a family known to be affected by HHS, the first presentation in adulthood, is intriguing. Clinical case: A 32-year old male presented with new-onset generalised non-convulsive seizures and family history of genetically proven HHS in his mother, two siblings and two of their offspring. A heterozygous missense mutation (R269H) in exon 7 of the GLUD1 gene was identified several years ago in this family. Our patient was screened clinically for hypoglycemia in childhood, but he never underwent genetic testing, as he was not considered affected. Affected family members developed confusion and hypoglycaemia following high-protein meals, which was reversed with glucose and limiting protein intake, lessened further attacks. Our patient’s school performance was poor and described feeling unwell after eating large protein meals. He was fully orientated, but his mini-mental state examination was impaired at 21/30. He was hyper-reflexic with spreading of ankle and crossed adductor reflexes. Considering his family history, we performed continuous glucose monitoring for 14 days, revealing several post-prandial and fasting hypoglycaemic episodes (as low as 1.8 mmol/L) and an HbA1c of 3.5%. HHS was proven (serum ammonia 70 µmol/L; normal less than 35 µmol/L) and genetic analysis revealed an identical mutation to the aforementioned. Diazoxide was titrated to abrogate hypoglycaemia. Genetic screening of the remaining family members will be undertaken. Clinical lessons: Among causes of PPH, HHS is rare. Missed diagnoses can have profound neurological and cognitive consequences. The intrafamilial variability is demonstrable however; it is likely that HHS was missed in our patient’s initial presentation in childhood, as seizures and intellectual disability in adulthood are exceptionally rare complications of this condition. It demonstrates that it is critical to perform genetic testing on all members of an affected family, even in those asymptomatic. Genetic diagnoses of PPH are rarely made in adulthood, as there is often a low diagnostic suspicion at such a late presentation.