Orphanet Journal of Rare Diseases (Aug 2024)

Acid sphingomyelinase deficiency in France: a retrospective survival study

  • Wladimir Mauhin,
  • Nathalie Guffon,
  • Marie T. Vanier,
  • Roseline Froissart,
  • Aline Cano,
  • Claire Douillard,
  • Christian Lavigne,
  • Bénédicte Héron,
  • Nadia Belmatoug,
  • Yurdagül Uzunhan,
  • Didier Lacombe,
  • Thierry Levade,
  • Aymeric Duvivier,
  • Ruth Pulikottil-Jacob,
  • Fernando Laredo,
  • Samia Pichard,
  • Olivier Lidove,
  • ASSUR Study Group

DOI
https://doi.org/10.1186/s13023-024-03234-6
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 12

Abstract

Read online

Abstract Background Acid sphingomyelinase deficiency (ASMD) or Niemann–Pick disease types A, A/B, and B is a progressive, life-limiting, autosomal recessive disorder caused by sphingomyelin phosphodiesterase 1 (SMPD1) gene mutations. There is a need to increase the understanding of morbidity and mortality across children to adults diagnosed with ASMD. Methods This observational retrospective survey analysed medical records of patients with ASMD with retrievable data from 27 hospitals in France, diagnosed/followed up between 1st January 1990 and 31st December 2020. Eligible records were abstracted to collect demographic, medical/developmental history, and mortality data. Survival outcomes were estimated from birth until death using Kaplan–Meier survival analyses; standardised mortality ratio (SMR) was also explored. Results A total of 118 medical records of patients with ASMD (type B [n = 94], type A [n = 15], and type A/B [n = 9]) were assessed. The majority of patients were males (63.6%); the median [range] age at diagnosis was 8.0 [1.0–18.0] months (type A), 1.0 [0–3] year (type A/B), and 5.5 [0–73] years (type B). Overall, 30 patients were deceased at the study completion date; the median [range] age at death for patients with ASMD type A (n = 14) was 1 [0–3.6] year, type A/B (n = 6) was 8.5 [3.0–30.9] years, and type B (n = 10) was 57.6 [3.4–74.1] years. The median [95% confidence interval (CI)] survival age from birth in patients with ASMD type A and type A/B was 2.0 [1.8–2.7] years and 11.4 [5.5–18.5] years, respectively. Survival analysis in ASMD type B was explored using SMR [95% CI] analysis (3.5 [1.6–5.9]), which showed that age-specific deaths in the ASMD type B population were 3.5 times more frequent than those in the general French population. The causes of death were mostly severe progressive neurodegeneration (type A: 16.7%), cancer (type B: 16.7%), or unspecified (across groups: 33.3%). Conclusions This study illustrated a substantial burden of illness with high mortality rates in patients with ASMD, including adults with ASMD type B, in France.

Keywords