title: Pulmonary manifestations in Niemann-Pick type C disease with mutations in NPC2 gene: case report and review of literature.
abstract: BACKGROUND
  Niemann-Pick disease type C (NPC) is an inherited metabolic disorder; due to defect in cellular cholesterol trafficking. It is clinically a heterogeneous disease with variable age of onset with multiple organ systems being involved. NPC1 gene is involved in 95% cases where as remaining ~5% cases are linked with NPC2 gene.
  
  
  METHODS
  Case-1, a 14-months-old female presented with recurrent respiratory distress, failure to thrive and hepatosplenomegaly. Lung biopsy was suggestive of alveolar proteinosis and liver biopsy confirmed foamy macrophages. Molecular analysis revealed homozygous mutation c.141C > A in exon 2 of NPC2 gene. Case-2, a 3-year-old male presented with dyspnoea and hepatomegaly noticed at 1 year of age. HRCT-scan of thoracic region showed consolidation with mediastinal lymphadenopathy. Broncho-alveolar lavage revealed moderate amount of foamy macrophages and bone marrow examination detected foam cells. Homozygous T > C transition in intron 1 of the NPC2 gene was identified.
  
  
  CONCLUSIONS
  Our study demonstrates that NPC2 can present in early years of life with pulmonary complications like alveolar proteinosis and hepatosplenomegaly or hepatomegaly due to mutation in NPC2 gene. An early suspicion will help clinicians to clinch its diagnosis, management and genetic counselling.
authors.affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India. jshethad1@gmail.com.
authors.forename: Jayesh
authors.identifier: http://orcid.org/0000-0001-5936-5192
authors.initials: J
authors.lastname: Sheth
authors.affiliation: Department of Pediatrics, Believers Church Medical College Hospital, Tiruvalla, Kerala, 689 101, India.
authors.forename: Jijo John
authors.initials: JJ
authors.lastname: Joseph
authors.affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.
authors.forename: Krati
authors.initials: K
authors.lastname: Shah
authors.affiliation: Department of Paediatrics, KEM Hospital, Parel, Mumbai, 400 012, India.
authors.forename: Mamta
authors.initials: M
authors.lastname: Muranjan
authors.affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.
authors.forename: Mehul
authors.initials: M
authors.lastname: Mistri
authors.affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.
authors.forename: Frenny
authors.initials: F
authors.lastname: Sheth
mesh_terms: D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008171:Lung Diseases / Q000209:etiology*; D008297:Male; D009154:Mutation; D052556:Niemann-Pick Disease, Type C / Q000235:genetics*; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; C104585:NPC2 protein, human; D033921:Vesicular Transport Proteins
keywords: Alveolar proteinosis; Case report; Hepatosplenomegaly; Lung involvement; Lysosomal Storage Disorders; NPC2 gene; Niemann-Pick disease type C