18º Congresso Brasileiro de Neurologia Infantil

Dados do Trabalho



Apresentação do caso

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.


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. Coursing with lysosomal storage disorder.
Presentations may be classified by age of onset, with overlapping phenotype. 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.

Comentários finais

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.

Referências (se houver)

FRAILE, P. Q. et al. Enfermedad de Niemann-Pick tipo C: desde una colestasis neonatal hacia un deterioro neurológico. Variabilidad fenotípica. Anales de Pediatría, v. 73, n. 5, p. 257–263, Nov 1st, 2010.
Orphanet: Niemann Pick disease type C. Available in: <https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=646>. Access at: Abr 20th, 2023.
Overview of Niemann-Pick disease - UpToDate. Available in: <https://www.uptodate.com/contents/overview-of-niemann-pick-disease?search=Niemann-Pick%20tipo%20C&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H12>. Access at: Abr 20th 2023.
PATTERSON, M. Niemann-Pick Disease Type C. GeneReviews®, Dec. 10th, 2020.
VANIER, M. T. Niemann-Pick disease type C. Orphanet Journal of Rare Diseases, v. 5, n. 1, p. 1–18, 3 jun. 2010.

Palavras Chave

Niemann-Pick type C, rare diseases, neuropediatrician, precocious

Declaração de conflito de interesses de TODOS os autores



Erros inatos do metabolismo


Hospital Pequeno Príncipe - Paraná - Brasil


Lorena Vilela Rezende, Daniel Almeida do Valle, Mara Lúcia Schmitz Ferreira Santos, Mariah Pereira de Andrade Vallim, Giulia Vilela Silva, Rui Carlos Silva Junior , Lisandra Coneglian de Farias Rigoldi , Andressa Taine Szczypkovski , Michelle da Silva Zeny