Institute of Clinical Sciences, Maria Skłodowska-Curie Medical Academy, Warsaw, Poland.
Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
Adv Clin Exp Med. 2024 Oct;33(10):1163-1168. doi: 10.17219/acem/193696.
Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive lysosomal storage disease (LSD) associated with biallelic pathogenic variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene.
The aim of this study was to provide the 2024 update on chronic visceral and neurovisceral ASMD diagnosed in the infancy/childhood in Polish patients.
All the patients diagnosed in the pediatric age (0-18 years) with ASMD, both chronic neurovisceral and visceral type, and then systematically followed up, were enrolled into the study.
A total number of 7 patients were enrolled into the study. Four patients were previously reported. Two patients were newly recognized with ASMD - 1 with chronic visceral and 1 with chronic neurovisceral ASMD. Splenomegaly was noted in all the patients while a mild liver enlargement was observed in 4 of 7 patients. All patients presented with decreased high-density lipoprotein cholesterol (HDL-C) and decreased serum 25-hydroxy-vitamin D concentration while almost all (6 of 7) with hypercholesterolemia. Cherry-red spot was observed in 5 of 7 patients, including 1 patient with neurovisceral type. Seven various SMPD1 gene variants were identified and missense variants were the most common types of genetic lesions, comprising 71% of all alleles. In all the screened patients, lyso-sphingomyelin (lyso-SM) in dried blood spot (DBS) was found elevated; however, the greater values were observed for patients with chronic neurovisceral type.
Chronic acid sphingomyelinase deficiency (ASMD) is a slowly progressive disease. Pediatric ASMD is characterized by spleno-hepatomegaly, dyslipidemia (with decreased HDL-C as the most characteristic) and infiltrative (interstitial) lung disease. Both visceral and neurovisceral chronic ASMD patients could present with cherry-red spot. Both acid spingomyelinase activity and lyso-spingomyelin concentration in DBS should be regarded as a first-tier screening method into ASMD.
酸性鞘磷脂酶缺乏症（ASMD）是一种常染色体隐性溶酶体贮积病（LSD），与鞘磷脂磷酸二酯酶 1（SMPD1）基因的双等位致病性变异相关。
本研究旨在提供波兰患者在婴儿/儿童期诊断的慢性内脏和神经内脏 ASMD 的 2024 年更新信息。
所有在儿科年龄（0-18 岁）被诊断为 ASMD 的患者，包括慢性神经内脏和内脏型，然后进行系统随访，均被纳入本研究。
共有 7 名患者被纳入研究。其中 4 名患者之前已被报道。新诊断为 ASMD 的 2 名患者中，1 名为慢性内脏型，1 名为慢性神经内脏型。所有患者均有脾肿大，7 名患者中有 4 名患者有轻度肝肿大。所有患者均有高密度脂蛋白胆固醇（HDL-C）降低和血清 25-羟维生素 D 浓度降低，而几乎所有患者（7 名患者中有 6 名）均有胆固醇升高。7 名患者中有 5 名出现樱桃红斑点，其中 1 名患有神经内脏型。共鉴定出 7 种不同的 SMPD1 基因突变，其中错义突变是最常见的遗传病变类型，占所有等位基因的 71%。在所有筛查的患者中，均发现干血斑（DBS）中的溶神经鞘磷脂（lyso-SM）升高；然而，慢性神经内脏型患者的数值更高。
慢性酸性鞘磷脂酶缺乏症（ASMD）是一种进展缓慢的疾病。儿科 ASMD 的特征是脾肿大、肝肿大、血脂异常（以高密度脂蛋白胆固醇降低为最特征性改变）和浸润性（间质）肺病。内脏和神经内脏慢性 ASMD 患者均可能出现樱桃红斑点。DBS 中的酸性鞘磷脂酶活性和溶神经鞘磷脂浓度均应视为 ASMD 的一线筛查方法。
