title: [Fatal neonatal respiratory distress in Niemann-Pick C2 and prenatal diagnosis with mutations in gene HE1/NPC2].
abstract: We report the fifth case of neonatal form of type C2 (NP-C2) Niemann-Pick disease with early and fatal respiratory distress. Eleven families presenting such cases are known to date in the world. Since December 2000, isolation of the underlying gene HE1/NPC2 and its mutations has allowed major advances in diagnosis.
  
  
  METHODS
  Elisa was born in May 2000. NP-C2 disease was associated with severe respiratory distress leading to death at the age of four months. On the next pregnancy in September 2000, prenatal diagnosis was performed by means of biological tests that required four weeks response time. In December 2000, isolation of the HE1/NPC2 gene located to 14q24.3 and of some of its mutations allowed to characterize the patient as being homozygote for the nonsense mutation E20X. On the the two next pregnancies, prenatal diagnosis was performed at 12 SA, in 48 hours, by the means of mutation analysis. The last fetus was heterozygote for the mutation E20X, allowing the birth at term of a healthy male newborn baby.
  
  
  CONCLUSIONS
  Niemann-Pick type C disease is a rare lysosomal lipid storage disease with severe prognosis. It is characterized by abnormalities of intracellular transport of endocytosed cholesterol. Diagnosis relies on biological tests that require cultured cells. Genetic heterogeneity defines two different genetic complementation groups C1 and C2. Severe and early respiratory distress is more likely to be associated with the rare type C2. Since December 2000, after identification of the disease-causing mutations in the proband, mutation analysis of gene HE1/NPC2 on direct chorionic villus samples allows early and fast (48 hours) prenatal diagnosis.
authors.affiliation: Service de réanimation et médecine néonatale, centre hospitalier de Lens, France. cmorisot@ch-lens.fr
authors.forename: C
authors.initials: C
authors.lastname: Morisot
authors.forename: G
authors.initials: G
authors.lastname: Millat
authors.forename: A
authors.initials: A
authors.lastname: Coeslier
authors.forename: B
authors.initials: B
authors.lastname: Bourgois
authors.forename: E
authors.initials: E
authors.lastname: Fontenoy
authors.forename: D
authors.initials: D
authors.lastname: Dobbelaere
authors.forename: L
authors.initials: L
authors.lastname: Verot
authors.forename: N
authors.initials: N
authors.lastname: Haouari
authors.forename: C
authors.initials: C
authors.lastname: Vaillant
authors.forename: F
authors.initials: F
authors.lastname: Gottrand
authors.forename: E
authors.initials: E
authors.lastname: Bogaert
authors.forename: P
authors.initials: P
authors.lastname: Thelliez
authors.forename: S
authors.initials: S
authors.lastname: Klosowski
authors.forename: A
authors.initials: A
authors.lastname: Djebara
authors.forename: A
authors.initials: A
authors.lastname: Bachiri
authors.forename: S
authors.initials: S
authors.lastname: Manouvrier
authors.forename: M T
authors.initials: MT
authors.lastname: Vanier
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D009542:Niemann-Pick Diseases / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications*; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; C104585:NPC2 protein, human; D033921:Vesicular Transport Proteins