title: Visceral symptoms as a key diagnostic sign for the early infantile form of Niemann-Pick disease type C in a Russian patient: a case report.
abstract: BACKGROUND
  Niemann-Pick disease type C is a rare metabolic disease characterized by progressive neurological deterioration with childhood onset, and often results in premature mortality. Niemann-Pick disease type C has an extremely heterogeneous clinical presentation with a wide range of visceral and neurological signs and symptoms that are not specific to the disease, and which progress over varied periods of time. The incidence and epidemiology of Niemann-Pick disease type C in Russia have not been characterized. We report the case of a Russian newborn with early-infantile onset Niemann-Pick disease type C who displayed prolonged neonatal jaundice and hepatosplenomegaly.
  
  
  METHODS
  A 5-year-old white boy born to non-consanguineous Russian parents was originally diagnosed with galactosemia at the age of 2 months based on a raised blood galactose level. A galactose-free and lactose-free diet resulted in achievement of a normal galactose level, but hepatosplenomegaly and cholestatic signs persisted. Liver biopsy results hinted at possible Niemann-Pick disease type C, but differential diagnostic investigations for progressive familial intrahepatic cholestasis type 2 (Byler syndrome) indicated a heterozygous genotype suggestive of this disease. Further, progressive neurological symptoms prompted additional genetic analyses for possible Niemann-Pick disease type C, from which an as-yet unreported combination of known NPC1 gene mutations was identified, and a final diagnosis of Niemann-Pick disease type C was established. The patient subsequently developed typical neurological symptoms of early-infantile Niemann-Pick disease type C, including vertical supranuclear ophthalmoparesis and cerebellar ataxia. Miglustat therapy was initiated 2.5 years ago, and some improvements in movement and speech have since been observed.
  
  
  CONCLUSIONS
  This case illustrates the continued challenges associated with diagnosing Niemann-Pick disease type C based on the appearance of nonspecific cholestatic symptoms. Based on this case we recommend examination of all newborns and children who display unexplained cholestasis or isolated splenomegaly/hepatosplenomegaly during the first months of life for other signs of possible Niemann-Pick disease type C.
authors.affiliation: Federal State Budget Institution, Research Center for Obstetrics, Gynecology and Perinatology, Federal State Budget Institution, 117997 Oparina str. 4, Moscow, Russia. annadim@yahoo.com.
authors.forename: A V
authors.initials: AV
authors.lastname: Degtyareva
authors.affiliation: Russian Children's Hospital, 117997 Leninsky Prospect 117, Moscow, Russia.
authors.forename: S V
authors.initials: SV
authors.lastname: Mikhailova
authors.affiliation: State Institution Medical Genetic Research Center, 115478, Moskvorechje str. 1, Moscow, Russia.
authors.forename: E Y
authors.initials: EY
authors.lastname: Zakharova
authors.affiliation: Russian National Research Medical University, 117997, Ostrovitjanova str. 1, Moscow, Russia.
authors.forename: E L
authors.initials: EL
authors.lastname: Tumanova
authors.affiliation: Federal State Budget Institution, Research Center for Obstetrics, Gynecology and Perinatology, Federal State Budget Institution, 117997 Oparina str. 4, Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Puchkova
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003951:Diagnostic Errors; D005693:Galactosemias / Q000175:diagnosis*; D005820:Genetic Testing; D065089:Glycoside Hydrolase Inhibitors / Q000627:therapeutic use; D006529:Hepatomegaly / Q000209:etiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000209:etiology; D008099:Liver / Q000473:pathology*; D008297:Male; D052556:Niemann-Pick Disease, Type C / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D012426:Russia; D013163:Splenomegaly / Q000209:etiology
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat
keywords: Cholestasis; Miglustat; Niemann–Pick disease type C; Splenomegaly