Effects of miglustat therapy on neurological disorder and survival in early-infantile Niemann-Pick disease type C: a national French retrospective study

Orphanet Journal of Rare Diseases

Research

François Labarthe¹  Philippe Latour²  Anaïs Brassier³  Samia Pichard³  Pierre Broué⁴  Caroline Sevin⁵  Claude Cances⁶  Cécile Freihuber⁷  Bénédicte Héron⁷  Brigitte Chabrol⁸  Didier Eyer⁹  Bahia Dahmani-Rabehi^1,10  Thierry Levade^1,11  Marie T. Vanier^1,12 

[1]CRMR ToTeM, Department of Pediatrics, Hôpital Clocheville, CHRU Tours, and Laboratoire N2C, Inserm U1069, Université François Rabelais de Tours, 37 000, Tours, France

[2]Department of Biochemistry and Molecular Biology, Hospices Civils de Lyon, Lyon, France

[3]Department of Metabolic Disorders, Reference Center for Inborn Errors of Metabolism, Necker-Enfants Malades University Hospital, Paris, France

[4]Department of Paediatric Hepatology and Metabolic Disorders, Reference Centre for Inborn Errors of Metabolism and Genetic Cholestasis, Children’s Hospital Toulouse University Hospitals, Toulouse, France

[5]Department of Paediatric Neurology, Kremlin-Bicêtre University Hospital, Paris, France

[6]Department of Paediatric Neurology, Purpan University Hospital, Toulouse, France

[7]Department of Paediatric Neurology, Reference Centre for Lysosomal Diseases, Armand Trousseau-La Roche Guyon Hospital and Hospital-University I2-D2 Federation, Sorbonne-Université, Paris, France

[8]Department of Paediatric Neurometabolism, La Timone University Hospital, Marseille, France

[9]Department of Paediatrics, Haguenau Hospital, Hagueneau, France

[10]Department of Paediatrics, Jean Verdier University Hospital, Bondy, France

[11]INSERM U1037 (Cancer Research Centre of Toulouse), Université Paul Sabatier, Toulouse, France

[12]Department of Clinical Biochemistry, Toulouse University Hospital, Toulouse, France

[13]Laboratoire Gillet-Mérieux, Lyon-East University Hospital, Hospices Civils de Lyon, Lyon, France

[14]INSERM U820, Lyon, France

关键词: Niemann-Pick disease type C;    Paediatric;    Early infantile;    Miglustat;    Efficacy;    Survival;    Safety;    France;   

DOI  :  10.1186/s13023-023-02804-4

 received in 2023-04-10, accepted in 2023-07-06,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNiemann-Pick disease type C (NP-C) is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurodegeneration and premature death. While miglustat can stabilize neurological manifestations in later onset forms of NP-C, its efficacy in the early-infantile neurological form has not been demonstrated. In this observational retrospective study, we compared long-term neurodevelopmental outcome and survival between an untreated and a treated group of early infantile NP-C patients.MethodsData available on all NP-C patients with early infantile neurological onset diagnosed in France between 1990 and 2013 were compiled. Patients with incomplete data or who had died from a systemic perinatal, rapidly fatal form were excluded.ResultsTen patients were included in the treated group (year of birth: 2006–2012), and 16 patients in the untreated group [born 1987–2005 (n = 15), 2012 (n = 1)]. The median age at neurological onset was 9 months (5–18) in the treated group, and 12 months (3–18) in the untreated group (p = 0.22). Miglustat therapy was started at a median age of 24.5 months (9–29) and median duration was 30 months (11–56). Gastrointestinal adverse events were reported in 7/10 patients on miglustat. All patients developed loss of psychomotor acquisitions or additional neurological symptoms despite miglustat therapy. The ages of developmental milestones and neurological involvement did not significantly differ between the two groups. Four patients in the untreated group were lost to follow up. The 22 remaining patients had died by the end of the study and no patient survived beyond the age of 7.4 years. The median survival age was 4.42 years in the untreated group and 5.56 years in the treated group; the Kaplan–Meier survival curves were not significantly different (log-rank test: p = 0.11).ConclusionsMiglustat allowed no significant long-term neurodevelopmental improvement nor significant increase of survival in patients with early infantile NP-C.

【 授权许可】

CC BY   
© The Author(s) 2023

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