Background: Diabetes mellitus is a late complication in glycogen storage disease type 1 (GSD1). Patients with GSD1 who are poorly controlled have prolonged periods of low glucose levels. As they grow older they become tolerant to these hypoglycaemic episodes, and may be mildly symptomatic or asymptomatic even with low glucose levels. This results in adaptive mechanisms, mediated through down regulation of glucose receptor on the β-cell membrane (GLUT2) to reduce insulin secretion. In time these patients develop a permanent state of insulinopaenia and lose their ability to secrete appropriate amounts of insulin in response to transient elevations of blood glucose. This hypothesis is the basis for the inclusion of GSD1 among genetic syndromes associated with secondary diabetes mellitus.
Case series: Patient one is a male who had first liver transplant at age of 11 years because of poor metabolic control secondary to GSD. He had rejection of his transplant following reactivation of CMV 4 years post-transplant and developed diabetes mellitus. He has been on twice daily insulin injections and his latest HbA1c is 81 mmol/mol. He has had two further transplants and has developed epilepsy, cataract and stage four kidney disease. Patient two is a female sibling who had liver transplant at age of 8 years for poor metabolic control secondary to GSD. She had few episodes of rejection but has recovered. She presented acutely unwell at 17 years with polyuria, polydipsia and acute abdominal distension and found to have graft dysfunction, acute renal failure and hyperglycaemia. She settled following insulin therapy and currently on insulin pump. Her latest HbA1c is 38 mmol/mol. She developed acute kidney injury during this episode but recovering well.
Summary: Only few cases have been reported so for. In our series siblings with GSD1b developed diabetes and it should be considered among the late complications of GSD-1b.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology