ESPE Abstracts

Background: While non-autoimmune T1D is rare in late childhood, few monogenic causes have yet been identified.

Objective: i) to identify the genetic basis of the yet unreported disease phenotype associating late childhood antibody-negative T1D, short stature, optic atrophy (OA), Pelger-Huët anomaly (PHA) of leukocytes and recurrent liver cytolysis: the ‘DISOPHAL’ syndrome; ii) to attract comparable cases for further genetic investigation.

Method: Whole-exome sequencing combined with genetic mapping of disease loci.

Results: Compound heterozygous mutations of neuroblastoma amplified sequence (NBAS) were found in three siblings of the same African family who had late childhood antibody-negative insulin-requiring T1D associated with dwarfism, OA, PHA and recurrent episodes of liver cytolysis.

Conclusion: NBAS is a new gene associated with non-autoimmune T1D. NBAS mutations have been reported before in non-diabetic patients with dwarfism, OA and PHA (‘SOPH’ syndrome) or a separate disorder of recurrent liver failure (‘RALF’ syndrome). NBAS mutations can induce a wide and heterogeneous clinical spectrum, which showed its complete form in our patients.