Long-term follow-up of diabetes in two patients with thiamine-responsive megaloblastic anemia syndrome

OBJECTIVE — To describe a 15-year follow-up of diabetes and to present data regarding pancreatic beta-cell function in two adolescents affected by the thiamine-responsive megaloblastic anemia (TRMA) syndrome. CASE REPORTS— The first patient (PMR) is a 17.5-year-old Italian girl who presented megaloblastic anemia at 7.5 months of age. At age 2.5 years, because of the presence of diabetes and sensorineural deafness, she was diagnosed with TRMA syndrome and started treatment with thamine-HCl, followed very early by benzoyloxymethyl-thiamine (BOM-T). The second patient (PF) is a 16.8-year-old Italian boy born to consanguineous parents. Sensorineural deafness was diagnosed at age 1.5 years, while diabetes with ketoacidosis and megaloblastic anemia were diagnosed at age 3 years. Treatment with thiamine HC1 was started immediately after diagnosis and changed to BOM-T 2 months later. Subsequent to the initiation of the vitamin, the two patients did not require insulin for ~7 and 10 years, respectively. Puberty was determinant in deteriorating the metabolic control in these patients, leading to treatment with an oral hypoglycemic agent and finally to a reinstitution of insulin therapy. CONCLUSIONS — The hormonal assessment in our patients (normal insulin response to oral glucose in childhood, preserved C-peptide secretion in case 2) and the good response to an oral hypoglycemic agent would indicate that the pancreatic disease may initiate as type 2 diabetes and may progress after several years to an insulin-requiring diabetes, as indicated by the exhaustion of the insulin secretory capacity.