title: The clinical spectrum of fetal Niemann-Pick type C.
abstract: Niemann-Pick type C (NPC) disease is a lysosomal neurovisceral storage disease. The spectrum of the clinical presentation as well as the severity of the disease and the age of presentation may be highly variable. Fetal presentation is rarely described in the literature. Here, we report on seven new cases of fetal onset NPC of whom two were diagnosed in utero and five postnatally. The fetal clinical presentation, included, in utero splenomegaly (6/7), in utero hepatomegaly (5/7), in utero ascites (4/7), intra uterine growth retardation (IUGR) (2/7), and oligohydramnios (2/7). Placentomegaly was present in two of the three pregnancies examined. Congenital thrombocytopenia (4/4), congenital anemia (2/4), and petechial rash (2/5) were diagnosed immediately after birth. Three patients were born preterm. Pregnancy and postnatal outcome were remarkably poor with one case of intrauterine fetal death, one elective termination of pregnancy, and four patients who died within the first months of life from a rapidly fatal neonatal cholestatic disease. NPC1 gene mutation analysis identified all of the mutant alleles including three novel mutations. Splenomegaly, hepatomegaly, and ascites were the most consistent prenatal ultrasonographic findings of the NPC fetuses. We suggest that once identified these findings, should raise the suspicion of fetal NPC. Our study further expands the antenatal clinical spectrum of NPC and provides clues to its prenatal diagnosis.
authors.affiliation: Genetic Institute, HaEmek Medical Center, Afula, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Spiegel
authors.forename: Annick
authors.initials: A
authors.lastname: Raas-Rothschild
authors.forename: Orit
authors.initials: O
authors.lastname: Reish
authors.forename: Miriam
authors.initials: M
authors.lastname: Regev
authors.forename: Vardiella
authors.initials: V
authors.lastname: Meiner
authors.forename: Ruth
authors.initials: R
authors.lastname: Bargal
authors.forename: Vivi
authors.initials: V
authors.lastname: Sury
authors.forename: Karen
authors.initials: K
authors.lastname: Meir
authors.forename: Michel
authors.initials: M
authors.lastname: Nadjari
authors.forename: Gratiana
authors.initials: G
authors.lastname: Hermann
authors.forename: Theodor C
authors.initials: TC
authors.lastname: Iancu
authors.forename: Stavit A
authors.initials: SA
authors.lastname: Shalev
authors.forename: Marsha
authors.initials: M
authors.lastname: Zeigler
mesh_terms: D001201:Ascites / Q000000981:diagnostic imaging / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005313:Fetal Death; D005333:Fetus; D006529:Hepatomegaly / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016464:Lysosomal Storage Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000175:diagnosis / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D013163:Splenomegaly / Q000000981:diagnostic imaging / Q000235:genetics*; D016216:Ultrasonography, Prenatal
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein