Endocrine Abstracts

Background: Familial Hyperinsulinaemic hypoglycaemia (FHH) is a very rare disease with heterogeneous clinical manifestation causing risk of late diagnosis or even misdiagnosis. In infants and children, it can lead to serious and permanent damage to the central nervous system. FHH has been correlated with mono-gene mutations in approximately 48% of cases. Clinical manifestation may vary even in the same affected GCK mutation family.

Objective: To describe the clinical presentation and metabolic profiles of affected family members with GCKc.295T>C(p.Trp99Arg) mutation.

Design: Clinical, biochemical and metabolic assessment, and GCK sequencing in affected family members.

Results: Family G: four family members from three generations affected (father, 2/3 children, grandson). A father of three children, age 54 (birth weight 3800g, current BMI-32), diagnosed at the age of 20 years. Symptoms of hypoglycaemia (HS) present from postnatal period, with an increased intensity in early childhood. Learning and behaviour problems during childhood. Hypoglycaemias:mild/severe, fasting/after the meal, no relation with physical activity/diet. Epilepsy diagnosed at age 10. Diazoxide: from the age of 20/some improvements/poor compliance. MRI/GLP-1 imaging not significant. Normal lipids/no liver steatosis. A son, age 25 (birth weight 4400 g, current BMI-25.9), diagnosed at the age of 4 years. HS from postnatal period, increased intensity in early childhood. School difficulties/problems with concentration. HS: mild/severe, fasting/overnight hypoglycaemias/after the meal/improvement after carbohydrate rich diet, no relation to physical activity/diet. Diazoxide: from age of 4, partial improvement/poor compliance. MRI not significant. Normal lipids/no liver steatosis. A daughter, age 23 (birth weight 3650 g, current BMI-23), diagnosed during postnatal period. HS: mild/severe, increased in early childhood. School difficulties/problems with concentration. HS: fasting/ after the meal, no relation with physical activity/diet. Diazoxide from postnatal period, some response/poor compliance. MRI not significant. Normal lipids/no liver steatosis. During early pregnancy (2014) severe hypoglycaemias, with response to steroid therapy, in the second/third trimester improvement. A grandson, age 3 (birth weight–3850 g, glucose after delivery 15 mg%). Immediate treatment with Diazoxide, no HS. Physical/psychological development is normal.

Conclusions: The clinical presentation of the disease is similar in the family members with GCK c.295T>C (p.Trp99Arg). Early diagnosis, diazoxide implementation/compliance are important in the course of the disease.