Introduction:We present the challenges of making a diagnosis in a child with global developmental delay in a resource limited setting and describe a new mutation causing GM2 gangliosidosis.

Method:Case review

Case description:11 month old male child presented with global developmental delay and focal seizure. Clinical examination revealed coarse facies, truncal hypotonia, spasticity at elbow and ankle joint. Investigations showed normal ammonia, lactate levels, TMS, abnormal LFT and EEG. MRI brain showed T1 and T2 shortening in bilateral thalami and basal ganglia and reduced NAA by spectroscopy. Following clinical exome study, ophthalmological examination revealed cherry red spot at macula. Neuroregression was noted at his next clinic review at 13 months of age. Reduced enzyme activity of hexosaminidase A+B was found in leukocytes.

Results:New mutation was found in clinical exome study at HEXB gene, intron 13, NM_000521.3:c.1614-2A>C, splice acceptor site variant, homozygous. Both parents were noted to be carriers.

Discussion:With the above clinical presentation, symmetric involvement of bilateral basal ganglia and thalami on MRI Brain is suggestive of systemic/metabolic causes.T1 hyperintensity of basal ganglia suggests differential diagnosis of GM1/GM2 gangliosidosis, Krabbe, Neuronal Ceroid Lipofuscinosis and Alexander disease. We did clinical exome sequencing first as this will have the highest yield and lowest cost and following this ,diagnosis was confirmed with low hexosaminidase (A+B) activity in leukocytes.

Conclusion:We present a previously unreported mutation causing GM2 Gangliosidosis.

References:OMIM. Johns Hopkins University, Baltimore, MD.MIM Number: (*606873): (07/14/2016): Web URL:https://omim.org/