Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 6978  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
  »  Article in PDF (802 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

  In this Article
 »  References

 Article Access Statistics
    PDF Downloaded62    
    Comments [Add]    

Recommend this journal


Table of Contents    
Year : 2015  |  Volume : 63  |  Issue : 4  |  Page : 626-628

Niemann-Pick type C disease in a 13-year-old boy from Nepal: A genetically confirmed case

1 Department of Neonatal, Division of Pediatric Neurology, Pediatric and Adolescent Medicine, BL Kapur (BLK) Super Speciality Hospital, New Delhi, India
2 Department of Pediatrics, Division of Pediatric Neurology, Lady Hardinge Medical College and Associated Kalawati Saran Children Hospital, New Delhi, India
3 Department of Pediatrics, B.P. Koirala Institute of Health Sciences, Dharan, Nepal
4 Department of Paediatrics and Adolescent Medicine, Albert-Schweitzer Campus, Münster, Germany
5 Department of Paediatrics and Adolescent Medicine, Albert-Schweitzer-Str. 33, Münster, Germany

Date of Web Publication4-Aug-2015

Correspondence Address:
Suvasini Sharma
Department of Pediatrics, Division of Pediatric Neurology, Lady Hardinge Medical College and Associated Kalawati Saran Children Hospital, New Delhi
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.162104

Rights and Permissions

How to cite this article:
Jain P, Sharma S, Poudel P, Reunert J, Marquardt T, Aneja S. Niemann-Pick type C disease in a 13-year-old boy from Nepal: A genetically confirmed case. Neurol India 2015;63:626-8

How to cite this URL:
Jain P, Sharma S, Poudel P, Reunert J, Marquardt T, Aneja S. Niemann-Pick type C disease in a 13-year-old boy from Nepal: A genetically confirmed case. Neurol India [serial online] 2015 [cited 2023 Dec 8];63:626-8. Available from:


Niemann-Pick disease type C is a rare neurodegenerative disorder caused by mutations in the NPC1 or the NPC2 gene. It has a variable age of onset and course with a heterogeneous clinical phenotype. [1],[2],[3] This makes the diagnosis challenging. We report a 13-year-old boy with Niemann-Pick disease type C with a predominant neurological phenotype.

This case was a 13-year-old Nepalese boy who presented with gait abnormalities noted for 6 months. He had no adverse peri-natal events and was developmentally normal. He had a progressively increasing frequency of falls for 6 months. He was also unsteady while walking. There was no difficulty in rising from sitting or lying position, and no history of a slapping gait or upper limb weakness. He had a poor scholastic performance with recent deterioration in speech. He spoke slowly with difficulty. There were no feeding difficulties. There was no history of seizures or loss of tone following laughter. The family history was unremarkable. He was born to a nonconsanguineous couple. Two other male siblings were normal.

Examination revealed vertical supranuclear gaze palsy (both saccadic and pursuit gaze palsy) [Video 1]. There were impaired voluntary and reflexive saccades with abnormal speed and range of movements. Other findings included a normal muscle tone, brisk muscle stretch-reflexes (including an ill-sustained clonus at ankle), cerebellar signs (score on brief ataxia rating scale [4] was 17/30), and orolingual and distal limb dyskinesia. There was no organomegaly and the fundus was normal.

Investigations showed a normal brain and cervical spine magnetic resonance imaging and a normal ultrasonography of the abdomen. Serum albumin, cholesterol, ceruloplasmin, copper, arterial blood gas, lactate and ammonia were normal. Serum alpha-fetoprotein, plasma acylcarnitine profile, plasma amino acids and urinary organic acids were normal. Bone marrow revealed increased histiocytes, few showing abundant foamy cytoplasm with occasional sea blue histiocytes. Mild hemophagocytosis was also seen. Filipin staining could not be done.

The score on NP-C suspicion index was 90 (scores > 70 warrants immediate testing for Niemann-Pick disease type C). [5] The plasma chitotriosidase activity was normal (52 nmol/h/ml; normal < 100 nmol/h/ml). The plasma cholestantriol levels were elevated (125 ng/mL; normal range < 50 ng/mL). The coding region including the flanking sequences of the NPC1 gene was sequenced. The mutations c. 302T > G F101C in exon 4 and IVS24 + 1G > A in the NPC1 gene were found in a heterozygous state. His father also showed the heterozygous mutation in IVS24 + 1G > A. This confirmed the diagnosis of Niemann-Pick type C disease.

The patient was started on supportive management. Miglustat could not be procured because of nonaffordability. Genetic counselling was done.

Niemann-Pick disease type C is a rare lysosomal storage disorder with a reported prevalence of 1 case in every 120,000 live-births. [1] The majority of the cases are due to mutations in the NPC1 or NPC2 gene. The gene defect leads to impaired cholesterol esterification and lipid trafficking as well as altered sphingolipid metabolism. [1],[3] More than 250 mutations are known in the NPC1 gene. [3] The NPC1 mutations in the reported case have not been described before. Only the variation IVS24 + 1G > C has been described in literature to be associated with the disease. [6] The reported cases from India are very sparse. [7],[8]

It is a neurovisceral disorder characterized by a variable phenotype depending on the age of onset of symptoms. The frequent neurological manifestations, reported from an international registry [2] were: Ataxia (70%), vertical supranuclear gaze palsy (70%), dysarthria (66%), cognitive impairment (62%) and dysphagia (52%). Vertical supranuclear gaze palsy is a strong clinical indicator of Niemann-Pick disease type C and has been reviewed elsewhere. [9] It may also be seen in other pediatric disorders like kernicterus, neurodegeneration associated with brain iron accumulation, spinocerebellar ataxias, ataxia telengiectasia, Tay-Sach disease, Leigh syndrome, etc. [9]

Similarly, the combination of cerebellar ataxia and dystonia strongly points towards the diagnosis of Niemann-Pick disease type C as in our case. However, this combination may also be encountered in late-onset GM2-gangliosidosis, Gaucher-disease type-3, ataxia with oculomotor apraxia type-1 and Leigh syndrome. Cataplexy is another specific symptom for Niemann-Pick disease type C especially seen in late-infantile (2-6 years) and juvenile-onset (6-15 years) cases. It was absent in our case.

Splenomegaly with or without hepatomegaly is common especially in early-onset cases. In older patients, mild splenomegaly may be detected only by abdominal ultrasound. [1] There was no organomegaly in our case both clinically and on investigation using an abdominal ultrasound.

Genetic testing is confirmatory. Histopathology (bone marrow, liver and skin) and filipin staining may be supportive. [1] Plasma chitotriosidase has low sensitivity and specificity for diagnosis of Niemann-Pick disease type C especially in juvenile-onset cases. [10] It was normal in our case. Oxysterols (cholesterol oxidation products) have been recently reported to be sensitive and specific markers for screening of Niemann-Pick disease type C. [1],[3],[11] Plasma cholestantriol, one of the cholesterol oxidation products, was elevated in our case. Plasma lysosphingolipid may also be a potential biomarker for Niemann-Pick disease type C. [12]

The prognosis is uniformly poor. Symptomatic treatment is pivotal. Miglustat (competitive inhibitor of glucosylceramide synthase, the enzyme involved in glycosphingolipid synthesis) may be offered to patients with neurological manifestations aiming at stabilizing the disease or reducing the rate of disease progression. [1] It is not available in India and Nepal currently.

Thus, the diagnosis of Niemann-Pick disease type C is challenging given the heterogenous nature of the clinical phenotype. Specific symptoms/signs (splenomegaly, vertical supranuclear gaze palsy, cataplexy, psychotic symptoms) and their combinations may suggest the diagnosis. [3],[5]

 » References Top

Patterson MC, Hendriksz CJ, Walterfang M, Sedel F, Vanier MT, Wijburg F, et al. Recommendations for the diagnosis and management of Niemann-Pick disease type C: An update. Mol Genet Metab 2012;106:330-44.  Back to cited text no. 1
Patterson MC, Mengel E, Wijburg FA, Muller A, Schwierin B, Drevon H, et al. Disease and patient characteristics in NP-C patients: Findings from an international disease registry. Orphanet J Rare Dis 2013;8:12.  Back to cited text no. 2
Mengel E, Klünemann HH, Lourenço CM, Hendriksz CJ, Sedel F, Walterfang M, et al. Niemann-Pick disease type C symptomatology: An expert-based clinical description. Orphanet J Rare Dis 2013;8:166.  Back to cited text no. 3
Schmahmann JD, Gardner R, MacMore J, Vangel MG. Development of a brief ataxia rating scale (BARS) based on a modified form of the ICARS. Mov Disord 2009;24:1820-8.  Back to cited text no. 4
Wijburg FA, Sedel F, Pineda M, Hendriksz CJ, Fahey M, Walterfang M, et al. Development of a suspicion index to aid diagnosis of Niemann-Pick disease type C. Neurology 2012;78:1560-7.  Back to cited text no. 5
Millat G, Marçais C, Tomasetto C, Chikh K, Fensom AH, Harzer K, et al. Niemann-Pick C1 disease: Correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop. Am J Hum Genet 2001;68:1373-85.  Back to cited text no. 6
Sheth JJ, Sheth FJ, Oza N. Niemann-Pick type C disease. Indian Pediatr 2008;45:505-7.  Back to cited text no. 7
Paul P, Mondal B, Mukherjee AK, Paul M, Kumar H. Unusually prominent horizontal gaze palsy in a case of Niemann-Pick type C disease. Ann Indian Acad Neurol 2013;16:279-81.  Back to cited text no. 8
[PUBMED]  Medknow Journal  
Salsano E, Umeh C, Rufa A, Pareyson D, Zee DS. Vertical supranuclear gaze palsy in Niemann-Pick type C disease. Neurol Sci 2012;33:1225-32.  Back to cited text no. 9
Pineda M, Wraith JE, Mengel E, Sedel F, Hwu WL, Rohrbach M, et al. Miglustat in patients with Niemann-Pick disease Type C (NP-C): A multicenter observational retrospective cohort study. Mol Genet Metab 2009;98:243-9.  Back to cited text no. 10
Jiang X, Sidhu R, Porter FD, Yanjanin NM, Speak AO, te Vruchte DT, et al. A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma. J Lipid Res 2011;52:1435-45.  Back to cited text no. 11
Welford RW, Garzotti M, Marques Lourenço C, Mengel E, Marquardt T, Reunert J, et al. Plasma lysosphingomyelin demonstrates great potential as a diagnostic biomarker for Niemann-Pick disease type C in a retrospective study. PLoS One 2014;9:e114669  Back to cited text no. 12


Print this article  Email this article
Online since 20th March '04
Published by Wolters Kluwer - Medknow