ESPE Abstracts

Background: NEUROD1 encoding neurogenic differentiation 1 is known to play an important role in the development of the pancreas and central nervous system. Heterozygous mutations have been rarely identified as a cause of maturity-onset diabetes of the young (MODY6). Biallelic NEUROD1 mutations have been reported to cause neonatal diabetes mellitus (NDM) as well. However, only 3 cases have been reported worldwide so far.

Case summary: We report a 4-month-old girl with NDM who presented only with abdominal distension to Alexandria University Children’s Hospital. She was born to consanguineous parents at 37 weeks of gestation, and was small for gestational age with a birth weight of 1.250 Kg (-4.41 SD). On examination, her weight was 4.200 Kg (-2.8 SD), length was 64 cm (+0.5 SD), and head circumference was 38 cm (-2.1 SD). She had hepatosplenomegaly, no lymphadenopathy, no jaundice or pallor. In addition, she had bilateral lower limb hypotonia, and head lag on pulling to sit. Her routine laboratory investigations revealed hyperglycemia (500 mg/dl) with normal venous blood gases. A diagnosis of NDM was confirmed with glycated haemoglobin of 13.4%, and low C-peptide level (0.197 ng/ml), and she was started on NPH insulin (requirements 1 U/Kg/day). Otherwise, her complete blood count, serum chemistry, and virology were normal. Audiometry showed bilateral sensori-neural hearing loss in the frequency range 2-4 KHz. She was suspected to have a mitochondrial cause of diabetes, so serum lactate was done and was mildly elevated. Her brain imaging showed hypoplasia of cerebellar vermis, enlarged posterior fossa, and cystic dilatation of 4^th ventricle. She had normal pancreatic size on abdominal sonography. Her electroencephalogram, nerve conduction velocity, echocardiography, and fundus examination were normal. Her genetic analysis revealed a novel homozygous likely pathogenic NEUROD1 missense variant [c.374G>C, p.(Arg125Pro)]. This variant has not been reported in the gnomAD database and affects a highly conserved residue within the DNA-binding domain. On follow-up, she developed generalized tonic convulsions in the absence of hypoglycemia and was diagnosed with epilepsy, so oral levetiracetam was added to her therapy with good control.

Conclusion: NDM patients with associated neurological abnormalities (especially cerebellar hypoplasia), and sensori-neural hearing loss should undergo genetic testing for NEUROD1. To our knowledge, this is the 4^th reported NDM case with NEUROD1 mutation worldwide and the first reported in Africa.