Iranian Journal of Child Neurology

Abstract

How to Cite This Article: Noroozi Asl S, Vakili R, Ghaemi N, Eshraghi P. The Report of Three Rare Cases of the Niemann-pick Disease in Birjand, South Khorasan, Eastern Iran. Iran J Child Neurol. Summer 2017; 11(3):53-56.

Abstract

Niemann–Pick disease type C (NP-C) is a rare neurovisceral and irreversible disease leading to premature death and disabling neurological signs. This autosomal recessive disease with incidence rate of 1:120000 is caused by mutations in either the NPC1 or the NPC2 gene, which leads to accumulation of cholesterol in body tissues especially brain and progressive neurological symptoms. NP-C is characterized by nonspecific visceral, neurological and psychiatric manifestations in infants. The neurological involvement is typically proceeded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno-or hepatosplenomegaly in infancy or childhood).

Early detection of NPC is important so that therapy with miglustat can delay onset of neurological symptoms and prolong survival. We describe here three infants from Birjand, South Khorasan, eastern Iran in 2016 with splenomegaly and different neurological signs that diagnosis was confirmed by genetic study. In all of them, NPC-509 was pathologically increased. They also had an unreported homozygous mutation (c. 1415T>C, p.Leu472Pro) in exon 9 of the NPC1 gene. We found unreported homozygous mutation in NPC gene.

Knowing this mutation is significant to our people. Genotype-phenotype correlations for this specific mutation needs to be further studied.

References

1. Mengel E, Klunemann H, Lourenco C, and et al. Niemann-Pick disease type C symptomatology: an expert-based clinical description. Orphanet J Rare Dis 2013;8:166.

2. Vanier MT: Niemann-Pick disease type C. Orphanet J Rare Dis 2010;5:16.

3. Di Rocco M1, Dardis A, Madeo A, Barone R, Fiumara A. Early miglustat therapy in infantile Niemann-Pick disease type C. Pediatr Neurol 2012;47(1):40-3.

4. Karimzadeh P, Tonekaboni SH, Ashrafi MR, et al. Effects of Miglustat on Stabilization of Neurological Disorder in Niemann–Pick Disease Type C Iranian Pediatric Case Series. J Child Neurol 2013;28(12):1599-606.

5. Wijburg F, Sedel F, Pineda M et al. Development of a Suspicion Index to aid diagnosis of Niemann-Pick disease type C. Neurology 2012;78(20):1560-7.

6. Wraith JE, Imrie J. New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat. Ther Clin Risk Manag 2009;5:877-87.

7. Patterson M, Hendriksz Ch, Walterfang M, et al. Recommendations for the diagnosis and management of Niemann–Pick disease type C: An update. Mol Genet Metab 2012;106(3):330-44.

8. Margaret M, Destinck DJ. Lipidosis(Lysosomal storage disease). Nelson Textbook of Pediatrics. 19th ed.

Philadelphia: WB Saunders Company. 2011:488-9.

9. Patterson M.C, Mengel E, Wijburg F, et al. Disease and patient characteristics in NP-C patients: findings from an international disease registry. Orphanet J Rare Dis 2013;8:12.