A Retrospective Multicentric Study of 34 Patients with Niemann–Pick Type C Disease and Early Liver Involvement in France - 14/03/23

Doi : 10.1016/j.jpeds.2022.10.015

Antoine Gardin, MD ^1,^⁎ , Charlotte Mussini, MD ², Bénédicte Héron, MD ³, Manuel Schiff, MD, PhD ^4,⁵, Anaïs Brassier, MD ⁴, Dries Dobbelaere, MD ⁶, Pierre Broué, MD ⁷, Caroline Sevin, MD, PhD ⁸, Marie T. Vanier, MD, PhD ⁹, Dalila Habes, MD ¹, Emmanuel Jacquemin, MD, PhD ^1,¹⁰, Emmanuel Gonzales, MD, PhD ^1,¹⁰
¹ 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
² Department of Pathology, Bicêtre Hospital, Le Kremlin-Bicêtre, France
³ 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
⁴ 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
⁵ Inserm UMR S1163, Institut Imagine, Université Paris Cité, Paris, France
⁶ 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
⁷ Department of Pediatric Hepatology, Reference Center for Inborn Error of Metabolism, Toulouse Children Hospital, Toulouse, France
⁸ Department of Pediatric Neurology, Bicêtre Hospital, Le Kremlin-Bicêtre, France
⁹ Inserm U820, Laboratoire Gillet-Mérieux, Hospices Civils de Lyon, Lyon, France
¹⁰ Inserm UMR S1193, Université Paris-Saclay, Hépatinov, Orsay, France

^∗Reprint requests: Antoine Gardin, MD, Pediatric Hepatology and Liver Transplant Department, Centre de Référence de l’Atrésie des Voies Biliaires et des Cholestases Génétiques, European Reference Network for Rare Hepatological Diseases (ERN 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, FrancePediatric Hepatology & Pediatric Liver Transplant DepartmentCentre de Référence de l’Atrésie des Voies Biliaires et des Cholestases GénétiquesERN RARE LIVERFilière de Santé des Maladies Rares du Foie de l'enfant et de l'adulteAssistance Publique-Hôpitaux de ParisFaculté de Médecine Paris-SaclayCHU BicêtreLe Kremlin-BicêtreFrance

Abstract

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.

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Keywords : NPC1, NPC2, Niemann–Pick disease, cholestasis, liver pathology

Abbreviations : 7-KC, AFP, ALT, AST, C-triol, γGT, HSCT, LysoSM, NP-C, PPCS, PT, ULN

Plan

Methods

Results

Initial Liver Involvement (within the First 6 Months of Life)

Liver Histology in Patients with NP-C

Diagnosis of NP-C

Liver Disease beyond Age 6 Months and General Outcome

Discussion

	The authors declare no conflicts of interest.
	Portions of this study were presented as a poster during the Groupe Francophone d’Hépatologie-Gastroentérologie et Nutrition Pédiatrique meeting, Bordeaux, France, April 1-2, 2022, and as a poster during the Société Française pour l’étude des erreurs innées du métabolisme meeting, Tours, France, June 27-28, 2022.

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Vol 254

P. 75 - mars 2023 Retour au numéro

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A Retrospective Multicentric Study of 34 Patients with Niemann–Pick Type C Disease and Early Liver Involvement in France - 14/03/23

Abstract

Objective

Study design

Results

Conclusions

Plan

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