Background: CD59 is a complement regulatory protein which inhibits membrane attack complex protecting self-cells from complement-mediated damage. Recent evidence suggests CD59 may suppress T cell activation via a complement-independent mechanism. Other than an immune regulator, CD59 is shown to regulate glucose stimulated insulin secretion. Herein we report a patient with inherited CD59 deficiency who developed type 1 diabetes.
Case: 11 year-old girl was admitted for polyuria and polydipsia. Previous history revealed intracranial bleeding at 6 months of age, acute motor axonal neuropathy in the course of otitis media at 18 months, and chronic Coombs negative intravascular hemolysis. Parents were first cousins, a sibling with similar symptoms died at 16 years. The patient had a homozygote missense mutation (c.A146T:p.Asp49Val) in the CD59 gene. She was on eculizumab for 2 years, and received aripiprazole for behavioral problems in the last year. In the family both parents, maternal grandmother, two paternal uncles and one aunt had diabetes. On PE she was prepubertal with normal height and weight, she had asymmetrical weakness and rigidity with distal atrophy in lower extremities, and a wide-based gait. Laboratory investigations revealed a blood glucose of 326 mg/dl with ketonuria, low insulin (2.4 uIU/ml) and c-peptide (1.38 ng/ml) levels. HbA1c was 9.1%, and antiGAD was positive (14.3 U/l N:<1). She was treated with insulin infusion at the ketotic state, and put on basal bolus insulin treatment.
Conclusion: A number of factors may have led to overt diabetes in the current patient, i.e. FH of diabetes, use of aripiprazole. Among them inherited CD59 deficency is a good candidate considering its suppressive role in MAC formation (in the light of recent evidence of complement deposition in T1DM pancreatic tissue suggesting possible involvement in pathogenesis), in complement independent T cell activation, and its role in glucose mediated insulin secretion.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology