Neurological features of late infantile Niemann Pick type C disease: case report

*Correspondence: [e-mail].

Abstract

Case Presentation: Female child at 2 months of age presented jaundice and transient hepatosplenomegaly. She underwent a liver biopsy with a diagnosis of neonatal hepatitis and an opportunistic cytomegalovirus infection was treated. Up to 2 years she had a normal neuropsychomotor development when she started a regression of the developmental milestone began, associated with progressive axial hypotonia and spastic tetraplegia, loss of speech, swallowing disorder, ptosis, and seizures. Physical examination showed a palpable spleen, vertical gaze supranuclear palsy and hyperreflexia. Abdominal ultrasound presented with homogeneous splenomegaly. Brain MRI had hypomyelinating leukodystrophy and diffuse thinning of the corpus callosum. At 3 years of age the diagnosis was identified 2 heterozygous pathogenic mutations in the gene NPC1 (c.3104C>T;p.A1035V and c.3689del;p.L1230fs). During clinical evolution 5 years, miglustat, levetiracetam and baclofen were started. Was performed gastrostomy and tracheostomy, evolved with refractory epilepsy and several hospitalizations due to infectious complications.

Discussion: Niemann Pick type C results from an autosomal recessive genetic alteration caused by pathogenic variants of the NPC1 and NPC2 genes that impair cholesterol transport course with lysosomal storage disorder. Presentations may be classified by age of onset, with overlapping phenotypes. Juvenile is the most common form, with onset in mid-childhood after normal early development with ataxia, vertical supranuclear ophthalmoplegia, dystonia, dysarthria, dysphagia, and epilepsy. The late infantile often presents with hypotonia and developmental delay. With time, vertical supranuclear saccadic palsy becomes apparent.

Final Comments: Abnormal NPC1 protein have demonstrated that this protein is indeed a necessary part of intracellular cholesterol trafficking that results in abnormal lipid metabolism, causing large amounts of nonesterified cholesterol and glucoside sphingolipids to deposit in lysosomes and consequent neurodegeneration. Once myelin sheath is the membrane that surrounds the axon of a nerve cell and has a high lipid content, mutations in the NPC1 gene could influence myelin formation. Leukodystrophy is more common in Severe early infantile and neurologic onset form, corroborating the hypothesis of overlap between disease phenotypes. So far there is no cure, only a possibility of stabilizing the neurological condition with Miglustat, a drug that inhibits the synthesis of glycolipids.

Publication History

Article published online:
12 May 2025