A Retrospective Multicentric Study of 34 Patients with Niemann-Pick Type C Disease and Early Liver Involvement in France.

Autor: Gardin A; Pediatric Hepatology and Liver Transplant Department, Centre de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, European Reference Network RARE-LIVER, Filière de Santé des Maladies Rares du Foie de l'Enfant et de l'Adulte, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Saclay, CHU Bicêtre, Le Kremlin-Bicêtre, France. Electronic address: antoine.gardin@gmail.com., Mussini C; Department of Pathology, Bicêtre Hospital, Le Kremlin-Bicêtre, France., Héron B; Department of Pediatric Neurology, Reference Center for Lysosomal Diseases, Armand Trousseau-La Roche Guyon Hospital, Assistance Publique-Hôpitaux de Paris, Fédération Hospitalo-Universitaire I2-D2, Sorbonne-Université, Paris, France., Schiff M; Reference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker-Enfants-Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Filière G2M, Paris, France; Inserm UMR S1163, Institut Imagine, Université Paris Cité, Paris, France., Brassier A; Reference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker-Enfants-Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Filière G2M, Paris, France., Dobbelaere D; Medical Reference Center for Inherited Metabolic Diseases, Jeanne de Flandre University Children's Hospital and Research Team for Rare Metabolic and Developmental Diseases (RADEME), EA 7364 CHRU Lille, Lille, France; MetabERN., Broué P; Department of Pediatric Hepatology, Reference Center for Inborn Error of Metabolism, Toulouse Children Hospital, Toulouse, France., Sevin C; Department of Pediatric Neurology, Bicêtre Hospital, Le Kremlin-Bicêtre, France., Vanier MT; Inserm U820, Laboratoire Gillet-Mérieux, Hospices Civils de Lyon, Lyon, France., Habes D; Pediatric Hepatology and Liver Transplant Department, Centre de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, European Reference Network RARE-LIVER, Filière de Santé des Maladies Rares du Foie de l'Enfant et de l'Adulte, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Saclay, CHU Bicêtre, Le Kremlin-Bicêtre, France., Jacquemin E; Pediatric Hepatology and Liver Transplant Department, Centre de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, European Reference Network RARE-LIVER, Filière de Santé des Maladies Rares du Foie de l'Enfant et de l'Adulte, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Saclay, CHU Bicêtre, Le Kremlin-Bicêtre, France; Inserm UMR S1193, Université Paris-Saclay, Hépatinov, Orsay, France., Gonzales E; Pediatric Hepatology and Liver Transplant Department, Centre de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, European Reference Network RARE-LIVER, Filière de Santé des Maladies Rares du Foie de l'Enfant et de l'Adulte, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Saclay, CHU Bicêtre, Le Kremlin-Bicêtre, France; Inserm UMR S1193, Université Paris-Saclay, Hépatinov, Orsay, France.
Jazyk: angličtina
Zdroj: The Journal of pediatrics [J Pediatr] 2023 Mar; Vol. 254, pp. 75-82.e4. Date of Electronic Publication: 2022 Oct 17.
DOI: 10.1016/j.jpeds.2022.10.015
Abstrakt: Objective: To describe the clinical features and course of liver involvement in a cohort of patients with Niemann-Pick type C disease (NP-C), a severe lysosomal storage disorder.
Study Design: Patients with genetically confirmed NP-C (NPC1, n = 31; NPC2, n = 3) and liver involvement before age 6 months were retrospectively included. Clinical, laboratory test, and imaging data were collected until the last follow-up or death; available liver biopsy specimens were studied using anti-CD68 immunostaining.
Results: At initial evaluation (median age, 17 days of life), all patients had hepatomegaly, 33 had splenomegaly, and 30 had neonatal cholestasis. Portal hypertension and liver failure developed in 9 and 4 patients, respectively. Liver biopsy studies, performed in 16 patients, revealed significant fibrosis in all 16 and CD68 + storage cells in 15. Serum alpha-fetoprotein concentration measured in 21 patients was elevated in 17. Plasma oxysterol concentrations were increased in the 16 patients tested. Four patients died within 6 months of life, including 3 from liver involvement. In patients who survived beyond age 6 months (median follow-up, 6.1 years), cholestasis regressed in all, and portal hypertension regressed in all but 1; 25 patients developed neurologic involvement, which was fatal in 16 patients.
Conclusions: Liver involvement in NP-C consisted of transient neonatal cholestasis with hepatosplenomegaly, was associated with liver fibrosis, and was responsible for death in 9% of patients. The combination of liver anti-CD68 immunostaining, serum alpha-fetoprotein measurement, and studies of plasma biomarkers should facilitate early identification of NP-C.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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