Villeneuve Thomas, Jamme Thibaut, Schwob Robin, Levade Thierry, Prévot Grégoire
Respiratory Medicine Department, University Hospital, Toulouse, France.
Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM U1291, CNRS U5282, University Toulouse III, Toulouse, France.
Orphanet J Rare Dis. 2025 May 26;20(1):252. doi: 10.1186/s13023-025-03746-9.
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.
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.
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.
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.
B型酸性鞘磷脂酶缺乏症（ASMD）是一种由SMPD1基因突变引起的罕见溶酶体疾病。由于其患病率低且临床异质性强，诊断具有挑战性，而检测对于启动酶替代疗法至关重要。
我们在图卢兹大学医院进行了一项回顾性研究（RnIPH 2024 - 85），分析了359,802份血脂谱（2012 - 2023年）。我们确定总胆固醇/高密度脂蛋白胆固醇比值>4.5的个体。一种基于正则表达式的提取方法筛选记录中的近亲结婚、肝肿大、脾肿大和磨玻璃影（GGO），同时我们还分析血小板减少症（<150×10⁹/L）。符合≥4/5条标准的患者接受临床评估。
在63,653例血脂异常患者中，20.3%有血小板减少症，4.93%有肝脾肿大，2.29%有GGO，0.24%有近亲结婚。共有179例患者符合≥4/5条标准。19例（10.6%）为儿童患者。我们中心确定了3例先前诊断为B型ASMD的患者。此外，在其他病症中，46例（25.7%）患有单基因疾病，5例未确诊患者被标记进行ASMD筛查。
我们的混合筛查有效地识别了B型ASMD病例和基因检测的潜在候选者。这种结合算法筛选和临床专业知识的方法可以提高B型ASMD的诊断率。
