Advanced strategies for detecting acid sphingomyelinase deficiency type B with attenuated phenotypes
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...
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BMC
2025-05-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03746-9 |
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| author | Thomas Villeneuve Thibaut Jamme Robin Schwob Thierry Levade Grégoire Prévot |
| author_facet | Thomas Villeneuve Thibaut Jamme Robin Schwob Thierry Levade Grégoire Prévot |
| author_sort | Thomas Villeneuve |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-806b51c84ded4b81bea5a817ce89775a |
| institution | DOAJ |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-806b51c84ded4b81bea5a817ce89775a2025-08-20T03:22:11ZengBMCOrphanet Journal of Rare Diseases1750-11722025-05-012011410.1186/s13023-025-03746-9Advanced strategies for detecting acid sphingomyelinase deficiency type B with attenuated phenotypesThomas Villeneuve0Thibaut Jamme1Robin Schwob2Thierry Levade3Grégoire Prévot4Respiratory Medicine Department, University HospitalClinical Biochemistry Laboratory, Reference Center for Inherited Metabolic Diseases, Federative Institute of Biology, University HospitalDigital and Data Management Department University HospitalClinical Biochemistry Laboratory, Reference Center for Inherited Metabolic Diseases, Federative Institute of Biology, University HospitalRespiratory Medicine Department, University HospitalAbstract 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.https://doi.org/10.1186/s13023-025-03746-9Rare disease diagnosisMetabolic diseaseASMD type BNiemann pick B disease |
| spellingShingle | Thomas Villeneuve Thibaut Jamme Robin Schwob Thierry Levade Grégoire Prévot Advanced strategies for detecting acid sphingomyelinase deficiency type B with attenuated phenotypes Orphanet Journal of Rare Diseases Rare disease diagnosis Metabolic disease ASMD type B Niemann pick B disease |
| title | Advanced strategies for detecting acid sphingomyelinase deficiency type B with attenuated phenotypes |
| title_full | Advanced strategies for detecting acid sphingomyelinase deficiency type B with attenuated phenotypes |
| title_fullStr | Advanced strategies for detecting acid sphingomyelinase deficiency type B with attenuated phenotypes |
| title_full_unstemmed | Advanced strategies for detecting acid sphingomyelinase deficiency type B with attenuated phenotypes |
| title_short | Advanced strategies for detecting acid sphingomyelinase deficiency type B with attenuated phenotypes |
| title_sort | advanced strategies for detecting acid sphingomyelinase deficiency type b with attenuated phenotypes |
| topic | Rare disease diagnosis Metabolic disease ASMD type B Niemann pick B disease |
| url | https://doi.org/10.1186/s13023-025-03746-9 |
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