Abstract
Niemann–Pick type C (NPC) disease is a recessive disorder that results in unesterified cholesterol accumulating in the lysosomal and late endosomal system. It is caused by mutations in NPC1 or NPC2 genes and leads to systemic and neurodegenerative symptoms. Few cases of prenatal presentation of NPC have been reported and only two cases in the absence of previous family history, indicating the diagnosis is particularly difficult in such a situation. We report a prenatal diagnosis of NPC in a couple without family history. An ultrasound screening at 22 weeks of gestation (WG) detected fetal ascites and hepatomegaly, which were still present at 25, 27, and 29 WG, and a splenomegaly progressively appeared. No placentomegaly or other signs of hydrops fetalis were observed. The diagnostic of NPC was prenatally confirmed by a filipin test and NPC1 sequencing and multiplex ligation-dependent probe amplification assay which revealed a maternal missense mutation (c.2608T>C; p.Ser870Pro) and a paternal deletion of exons 5 to 25. This additional prenatal case of NPC suggests that even in the absence of family history, fetal ascites associated with splenomegaly but no hydrops should nonetheless arouse suspicion concerning this disease as a possible diagnosis.
Competing interests: None declared
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Communicated by: Maurizio Scarpa, M.D, Ph.D
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Take-Home Message
This additional prenatal case of NPC suggests that even in the absence of family history, fetal ascites associated with splenomegaly but no hydrops should nonetheless arouse suspicion concerning this disease as a possible diagnosis.
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EC, LS, DB wrote the paper, PL and GPL did the filipin test and the sequencing of NPC1 and NPC2, AG and AZ did the cytogenetic test, EC and MB provided the genetic counseling, FB carried out the ultrasound examination, DL performed the fetal magnetic resonance imaging, and ST performed the histological examination.
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E. Colin, D. Bonneau, M. Barth, F. Boussion, P. Latour, G. Piguet-Lacroix, A. Guichet, A. Ziegler, S. Triau, D. Loisel, and L. Sentilhes declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from the patient to be included in the report.
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Colin, E. et al. (2015). In Utero Diagnosis of Niemann–Pick Type C in the Absence of Family History. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 28. JIMD Reports, vol 28. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_516
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DOI: https://doi.org/10.1007/8904_2015_516
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