Identification of a diffuse form of hyperinsulinemic hypoglycemia by 18-fluoro-L-3,4 dihydroxyphenylalanine positron emission tomography/CT in a patient carrying a novel mutation of the HADH gene

Objective: Familial hyperinsulinism is the most common cause of hypoglycemia in infancy (HI), leasing to severe neurologic disabilities if not promptly treated. The recent application of positron emission tomography (PET/CT) scanning with 18F-DOPA has improved the capa-bility to distinguish the two histopathologic forms of HI (focal and diffuse), whose differen-tiation heavily influences the therapeutic management of the patient. Case report: We describe the case of a patient presenting severe hypoglycemia from infancy. High concentration of insulin suggested the diagnosis of congenital hyperinsulinism. Medical treatment was able to obtain a satisfactory metabolic response. Results: The patient underwent PET/CT scanning, revealing a diffuse form of the disease. The absence of mutations in KCNJ11 and ABCC88 genes (responsible for 50% of HI familial cases), and whole genome single nucleotide polymorphisms analysis by microarray suggested the HADH gene as a likely candidate in this case. Sequence analysis revealed a novel homo-zygous nonsense mutation (R236X) in HADH gene. Conclusions: This case indicate that mutations of HADH gene should be sought in hyperin-sulinemic patients in whom diffuse form of HI and autosomal recessive inheritance can be presumed, when KCNJ11 and ABCC88 genes mutational screening is negative