P81 – 2663: Niemann-Pick type C disease in a child with a novel NPC1 mutation

Abstract

Objective Niemann-Pick type C is an autosomal recessive degenerative disease that can present in infancy, childhood, or adulthood. It is characterized by accumulation of free cholesterol and glycosphingolipids in the endosomal-lysosomal system, and is caused by mutations in the NPC1 or NPC2 gene. To date, Approximately 200 mutations have been described in Niemann-Pick type C1, but no homozygous V1023I (GTT>ATT) mutation have yet been reported. Methods We report a 13-year-old girl born to a first degree consanguineously married couple at term by normal delivery. The patient's history indicated that she was diagnosed with epilepsy for eight months. A month before referral to the hospital, her seizure had gone out of control and despite the patient's frequent visits and increased drug dose, the treatment had not been successful. On examination the patient had vertical supranuclear ophthalmoplegia. Slow speech, dysarthria, head titubation and truncal ataxia were noted. Ultrasonography of abdomen shows moderately enlarged liver and spleen. MRI of brain was normal. This presentation was suggestive of a lysosomal storage disorder and lysosomal enzyme activity and genetic testing was performed. Results The analysis of the NPC 1 gene identified a homoallelic V1023I (GTT>ATT) mutation. Both parents were heterzygous carriers of V1023I (GTT>ATT) mutation in the NPC 1 gene. Conclusion Niemann-Pick type C is a neurovisceral disease, with a highly heterogeneous presentation and is characterized by progressive neurological deterioration. Patients can show visceral, neurological and psychiatric manifestations which present alone or in different combinations To the best of our knowledge, this is the first report of a novel homozygous V1023I (GTT>ATT) mutation in NPC1 gene which is associated with Niemann-Pick type C disease.