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. 2025 May 26;20(1):252.
doi: 10.1186/s13023-025-03746-9.

Advanced strategies for detecting acid sphingomyelinase deficiency type B with attenuated phenotypes

Thomas Villeneuve  1   2 , Thibaut Jamme  3 , Robin Schwob  4   5 , Thierry Levade  3   6 , Grégoire Prévot  7
Affiliations

Advanced strategies for detecting acid sphingomyelinase deficiency type B with attenuated phenotypes

Thomas Villeneuve et al. Orphanet J Rare Dis. .

Abstract

Background: Acid Sphingomyelinase Deficiency (ASMD) type B is a rare lysosomal disorder caused by SMPD1 mutations. Due to its low prevalence and clinical heterogeneity, diagnosis is challenging, and detection is crucial for the initiation of enzyme replacement therapy.

Methods: We conducted a retrospective study (RnIPH 2024-85) at Toulouse University Hospital, analyzing 359,802 lipid profiles (2012-2023). We identified individuals with a total cholesterol/HDL cholesterol ratio > 4.5. A regex-based extraction method screened records for consanguinity, hepatomegaly, splenomegaly, and ground-glass opacities (GGOs), while we also analyzed thrombocytopenia (< 150 × 10⁹/L). Patients meeting ≥ 4/5 criteria underwent clinical review.

Results: Among 63,653 patients with dyslipidemia, 20.3% had thrombocytopenia, 4.93% hepatosplenomegaly, 2.29% GGOs, and 0.24% consanguinity. In total, 179 patients met ≥ 4/5 criteria. Nineteen (10.6%) were pediatric. Three previously diagnosed ASMD type B patients in our center were identified. Additionally, among other conditions, 46 cases (25.7%) had monogenic diseases, and five undiagnosed patients were flagged for ASMD screening.

Conclusion: Our hybrid screening effectively identified ASMD type B cases and potential candidates for genetic testing. This approach combining algorithmic filtering and clinical expertise, could enhance ASMD type B diagnosis.

Keywords: ASMD type B; Metabolic disease; Niemann pick B disease; Rare disease diagnosis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This retrospective study, conducted at Toulouse University Hospital (RnIPH 2024-85), is exempt from Ethics Committee submission under French law and complies with MR-004 methodology and GDPR regulations (EU 2016/679). It is registered with CNIL (2206723 v 0), ensuring full adherence to ethical standards. Consent for publication: Not applicable. Competing interests: TV, TJ, and RS have nothing to declare. TL declares that over the past four years, consultation agreements have been established through INSERM or CHU Toulouse for a contract providing financial support for investigator-initiated research (Sanofi) and for honoraria received for presentations (Sanofi-Aventis, Chiesi) or consulting (Aceragen); payments were made to INSERM or CHU Toulouse. GP declares that over the past four years, he has received honoraria for presentations as an oral speaker for Sanofi.

Figures

Fig. 1
Fig. 1
The Venn diagram illustrates the overlap between all types of conditions compatible with ASMD among selected patients with a cholesterol risk ratio > 4.5 (n = 63 653). The numbers represent the cohort of patients derived from the total population. Individuals with a confirmed diagnosis of ASMD who met four or five diagnostic criteria are represented by grey points. Abbreviations: CT: Computed Tomography; GGOs: Ground-Glass Opacities
See this image and copyright information in PMC

References

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