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.

Impact of selected inborn errors of metabolism on prenatal and neonatal development

“…Fetal presentation has been described only in few case reports. These patients were born prematurely with pronounced hepatosplenomegaly and ascites (38)(39)(40). Intrauterine growth retardation, oligohydramnion, congenital thrombocytopenia, and anemia were present as well.…”

Gene Therapy for the Treatment of Neurological Disorders: Metabolic Disorders

“…NPC can become symptomatic between infancy and adulthood [17], with cognitive dysfunction, ataxia, dysarthria and loss of language [18]. Although, severity of symptoms might differ along with the onset of symptoms, most patients die between the ages of 10 and 25.…”

“…Although, severity of symptoms might differ along with the onset of symptoms, most patients die between the ages of 10 and 25. Of note, even fetal NPC has been described [17]. …”

Niemann–Pick type C: a potentially treatable disorder?

“…About 95% of patients have NPC1 gene mutations, encoding the NPC1 protein; this is a large membrane glycoprotein predominantly located within the late endosomal membrane but is also transiently associated with lysosomes and the trans-Golgi network. It plays a role in LDL cholesterol intracellular trafficking, plasma levels and distribution 8 9. Disrupting this trafficking allows lipid accumulation with resulting neurological and hepatic manifestations 10…”