We report the case of a 19 years old male patient suffering from a multisystem disease involving of the skeleton, connective tissue, immune system, brain and endocrine system due to compound-heterozygote mutations in the NBAS (Neuroblastoma amplified sequence) gene (c.5741G>A [p.(Arg1914His)]; c.6565_6566insT [p.(Glu2189Valfs*7)]), detected using whole-exome-sequencing. He has an immunodeficiency including decreased CD4+T-cells, B-cells and NK-cells with expanded early CD8+ effector and activated T-cells, and absence of immunoglobulins, which requires regular substitution with immunoglobulins. At the age of 11 years, Insulin-dependent Diabetes mellitus was diagnosed. At the age of 19 years, C-peptide is low, but still measurable. The patient has an extremely short stature (125 cm; height-SDS: −10.7) and is dystrophic (weight 27 kg, BMI 17.3 mg/m2, BMI-SDS: −2.1). Moreover, he has a cerebellar hypotrophy and skeletal deformities. The phenotypic variability of patients with NBAS deficiency highlights that mutations in NBAS lead to a clinical spectrum ranging from isolated acute liver failure to a multisystem phenotype including short stature, skeletal dysplasia, and immunological abnormalities. Although immunodeficiency and also autoimmune disorders including Celiac disease and Crohns disease have already been published in patients with NBAS deficiency, no patient with Insulin-dependent Diabetes mellitus has been described so far. In conclusion, we describe the first patient with an Insulin-dependent Diabetes mellitus due to NBAS mutations. Probably, the immune dysregulation promoted the development of the Diabetes in our patient.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology