Abstract
WE DESCRIBE FOUR PATIENTS WITH NIEMANN—Pick disease type C (NPC), in whom the presentation was isolated splenic enlargement; this remained the only abnormality for a number of years. Diagnosis can be suggested by either finding abnormal storage material in a tissue biopsy specimen or by showing a modest elevation in plasma chitotriosidase activity. In patients with suggestive abnormalities, filipin staining of a skin fibroblast sample should confirm the abnormality in cholesterol trafficking. Formal esterification studies and mutation analysis should also be performed, especially if prenatal testing is to be performed in subsequent pregnancies. If the diagnosis is not considered and established, the family are at risk of having further affected children. Investigation of patients with isolated splenomegaly is not complete until NPC has been excluded.
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- Erickson R. P., Garver W. S., Camargo F., Hossain G. S., Heidenreich R. A. Pharmacological and genetic modifications of somatic cholesterol do not substantially alter the course of CNS disease in Niemann-Pick C mice. J Inherit Metab Dis. 2000 Feb;23(1):54–62. doi: 10.1023/a:1005650930330. [DOI] [PubMed] [Google Scholar]
- Fensom A. H., Grant A. R., Steinberg S. J., Ward C. P., Lake B. D., Logan E. C., Hulman G. An adult with a non-neuronopathic form of Niemann-Pick C disease. J Inherit Metab Dis. 1999 Feb;22(1):84–86. doi: 10.1023/a:1005463718823. [DOI] [PubMed] [Google Scholar]
- Fink J. K., Filling-Katz M. R., Sokol J., Cogan D. G., Pikus A., Sonies B., Soong B., Pentchev P. G., Comly M. E., Brady R. O. Clinical spectrum of Niemann-Pick disease type C. Neurology. 1989 Aug;39(8):1040–1049. doi: 10.1212/wnl.39.8.1040. [DOI] [PubMed] [Google Scholar]
- Hsu Y. S., Hwu W. L., Huang S. F., Lu M. Y., Chen R. L., Lin D. T., Peng S. S., Lin K. H. Niemann-Pick disease type C (a cellular cholesterol lipidosis) treated by bone marrow transplantation. Bone Marrow Transplant. 1999 Jul;24(1):103–107. doi: 10.1038/sj.bmt.1701826. [DOI] [PubMed] [Google Scholar]
- Millat G., Marçais C., Rafi M. A., Yamamoto T., Morris J. A., Pentchev P. G., Ohno K., Wenger D. A., Vanier M. T. Niemann-Pick C1 disease: the I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype. Am J Hum Genet. 1999 Nov;65(5):1321–1329. doi: 10.1086/302626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neville B. G., Lake B. D., Stephens R., Sanders M. D. A neurovisceral storage disease with vertical supranuclear ophthalmoplegia, and its relationship to Niemann-Pick disease. A report of nine patients. Brain. 1973;96(1):97–120. doi: 10.1093/brain/96.1.97. [DOI] [PubMed] [Google Scholar]
- Omarini L. P., Frank-Burkhardt S. E., Seemayer T. A., Mentha G., Terrier F. Niemann-Pick disease type C: nodular splenomegaly. Abdom Imaging. 1995 Mar-Apr;20(2):157–160. doi: 10.1007/BF00201528. [DOI] [PubMed] [Google Scholar]
- Pentchev P. G., Comly M. E., Kruth H. S., Vanier M. T., Wenger D. A., Patel S., Brady R. O. A defect in cholesterol esterification in Niemann-Pick disease (type C) patients. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8247–8251. doi: 10.1073/pnas.82.23.8247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schofer O., Mischo B., Püschel W., Harzer K., Vanier M. T. Early-lethal pulmonary form of Niemann-Pick type C disease belonging to a second, rare genetic complementation group. Eur J Pediatr. 1998 Jan;157(1):45–49. doi: 10.1007/s004310050764. [DOI] [PubMed] [Google Scholar]
- Vanier M. T., Rodriguez-Lafrasse C., Rousson R., Mandon G., Boué J., Choiset A., Peyrat M. F., Dumontel C., Juge M. C., Pentchev P. G. Prenatal diagnosis of Niemann-Pick type C disease: current strategy from an experience of 37 pregnancies at risk. Am J Hum Genet. 1992 Jul;51(1):111–122. [PMC free article] [PubMed] [Google Scholar]
- Watari H., Blanchette-Mackie E. J., Dwyer N. K., Glick J. M., Patel S., Neufeld E. B., Brady R. O., Pentchev P. G., Strauss J. F., 3rd Niemann-Pick C1 protein: obligatory roles for N-terminal domains and lysosomal targeting in cholesterol mobilization. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):805–810. doi: 10.1073/pnas.96.3.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yan-Go F. L., Yanagihara T., Pierre R. V., Goldstein N. P. A progressive neurologic disorder with supranuclear vertical gaze paresis and distinctive bone marrow cells. Mayo Clin Proc. 1984 Jun;59(6):404–410. doi: 10.1016/s0025-6196(12)61464-5. [DOI] [PubMed] [Google Scholar]