Prenatal revelation of Niemann–Pick disease type C in siblings

Moreno, Rubén; Drouin‐Garraud, Valérie; Verspyck, É.; Marret, Stéphane; Laquerrière, Annie

doi:10.1111/j.1651-2227.2008.00829.x

Cited by 17 publications

(5 citation statements)

References 10 publications

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“…This report is, to our knowledge, the third case of fetalonset NPC diagnosed in utero in the absence of a previous case in the family (Spiegel et al 2009). To date, fourteen cases of prenatal-onset NPC have been reported in the literature (Maconochie et al 1989;Manning et al 1990;Moreno et al 2008;Spiegel et al 2009;Surmeli-Onay et al 2013;Baumk€ otter et al 1998). Table 1 shows that cardinal features were splenomegaly (8/10, 80% of the documented cases), ascites (11/14, 78.5%), hepatomegaly (6/10, 60% of the documented cases), and placentomegaly (5/6, 83% of the documented cases).…”

Section: Discussionmentioning

confidence: 63%

In Utero Diagnosis of Niemann–Pick Type C in the Absence of Family History

et al. 2015

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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.

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Section: Discussionmentioning

confidence: 63%

In Utero Diagnosis of Niemann–Pick Type C in the Absence of Family History

et al. 2015

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“…The second patient with similar clinical findings survived without progressive ascites or liver failure. Siblings with the same molecular defect may have different disease outcomes and variable presentation and severity of perinatal onset NPD-C[ 61 ].…”

Section: Npd Type Cmentioning

confidence: 99%

Natural history and management of liver dysfunction in lysosomal storage disorders

Sarma¹,

Tripathi²

2022

World J Hepatol

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Lysosomal storage disorders (LSD) are a rare group of genetic disorders. The major LSDs that cause liver dysfunction are disorders of sphingolipid lipid storage [Gaucher disease (GD) and Niemann-Pick disease] and lysosomal acid lipase deficiency [cholesteryl ester storage disease and Wolman disease (WD)]. These diseases can cause significant liver problems ranging from asymptomatic hepatomegaly to cirrhosis and portal hypertension. Abnormal storage cells initiate hepatic fibrosis in sphingolipid disorders. Dyslipidemia causes micronodular cirrhosis in lipid storage disorders. These disorders must be keenly differentiated from other chronic liver diseases and non-alcoholic steatohepatitis that affect children and young adults. GD, Niemann-Pick type C, and WD also cause neonatal cholestasis and infantile liver failure. Genotype and liver phenotype correlation is variable in these conditions. Patients with LSD may survive up to 4-5 decades except for those with neonatal onset disease. The diagnosis of all LSD is based on enzymatic activity, tissue histology, and genetic testing. Enzyme replacement is possible in GD and Niemann-Pick types A and B though there are major limitations in the outcome. Those that progress invariably require liver transplantation with variable outcomes. The prognosis of Niemann-Pick type C and WD is universally poor. Enzyme replacement therapy has a promising role in cholesteryl ester storage disease. This review attempts to outline the natural history of these disorders from a hepatologist’s perspective to increase awareness and facilitate better management of these rare disorders.

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“…NPC1 disease has an extremely variable clinical presentation, including an age of onset that ranges from in utero to adulthood [14][15][16]. The current NPC1 literature primarily describes the most commonly occurring infantile and juvenile ages of onset, with very few studies focused on pre/perinatal cases with an age of onset before 2 months [14,[16][17][18][19][20][21][22]. NPC1 patients suffering from this earlier presentation are characterized by more notable visceral clinical findings, such as splenomegaly and/or hepatomegaly as well as ascites (summarized in [22]); in contrast, later onset patients manifest the classical neurodegenerative symptoms of NPC1 [14].…”

Section: Introductionmentioning

confidence: 99%

NPC1 Deficiency in Mice is Associated with Fetal Growth Restriction, Neonatal Lethality and Abnormal Lung Pathology

Rodriguez-Gil

Watkins‐Chow

Baxter

et al. 2019

JCM

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The rare lysosomal storage disorder Niemann-Pick disease type C1 (NPC1) arises from mutation of NPC1, which encodes a lysosomal transmembrane protein essential for normal transport and trafficking of cholesterol and sphingolipids. NPC1 is highly heterogeneous in both clinical phenotypes and age of onset. Previous studies have reported sub-Mendelian survival rates for mice homozygous for various Npc1 mutant alleles but have not studied the potential mechanisms underlying this phenotype. We performed the first developmental analysis of a Npc1 mouse model, Npc1 em1Pav , and discovered significant fetal growth restriction in homozygous mutants beginning at E16.5. Npc1 em1Pav/em1Pav mice also exhibited cyanosis, increased respiratory effort, and over 50% lethality at birth. Analysis of neonatal lung tissues revealed lipid accumulation, notable abnormalities in surfactant, and enlarged alveolar macrophages, suggesting that lung abnormalities may be associated with neonatal lethality in Npc1 em1Pav/em1Pav mice. The phenotypic severity of the Npc1 em1Pav model facilitated this first analysis of perinatal lethality and lung pathology in an NPC1 model organism, and this model may serve as a useful resource for developing treatments for respiratory complications seen in NPC1 patients.

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Prenatal revelation of Niemann–Pick disease type C in siblings

Cited by 17 publications

References 10 publications

In Utero Diagnosis of Niemann–Pick Type C in the Absence of Family History

In Utero Diagnosis of Niemann–Pick Type C in the Absence of Family History

Natural history and management of liver dysfunction in lysosomal storage disorders

NPC1 Deficiency in Mice is Associated with Fetal Growth Restriction, Neonatal Lethality and Abnormal Lung Pathology

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