Acid ceramidase deficiency is an orphan lysosomal disorder caused by ASAH1 pathogenic variants and presenting with either Farber disease or spinal muscle atrophy with progressive myoclonic epilepsy (SMA‐PME). Phenotypic and genotypic features are rarely explored beyond the scope of case reports. Furthermore, the new biomarker C26‐Ceramide requires validation in a clinical setting. We evaluated the clinical, biomarker and genetic spectrum of 15 Egyptian children from 14 unrelated families with biallelic pathogenic variants in ASAH1 (12 Farber and 3 SMA‐PME). Recruited children were nine females/six males ranging in age at diagnosis from 13 to 118 months. We detected ASAH1 pathogenic variants in all 30 alleles including three novel variants (c.1126A>G (p.Thr376Ala), c.1205G>A (p.Arg402Gln), exon‐5‐deletion). Both total C26‐Ceramide and its trans‐ isomer showed 100% sensitivity for the detection of ASAH1‐related disorders in tested patients. A 10‐year‐old girl with the novel variant c.1205G>A (p.Arg402Gln) presented with a new peculiar phenotype of PME without muscle atrophy. We expanded the phenotypic spectrum of ASAH1‐related disorders and validated the biomarker C26‐Ceramide for supporting diagnosis in symptomatic patients.

中文翻译：

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ASAH1 相关疾病：15 名新型儿科患者的描述和临床表型的扩展。

酸性神经酰胺酶缺乏症是一种由ASAH1致病变异引起的孤儿溶酶体疾病，表现为法伯病或脊髓肌肉萎缩伴进行性肌阵挛性癫痫（SMA-PME）。表型和基因型特征很少超出病例报告的范围。此外，新的生物标志物 C26-神经酰胺需要在临床环境中进行验证。我们评估了来自 14 个不相关家庭的 15 名埃及儿童的临床、生物标志物和遗传谱，这些儿童在ASAH1 中具有双等位基因致病变异（12 个 Farber 和 3 个 SMA-PME）。招募的儿童是 9 名女性/6 名男性，诊断时的年龄从 13 个月到 118 个月不等。我们检测到ASAH1所有 30 个等位基因中的致病变异，包括三个新变异（c.1126A>G（p.Thr376Ala）、c.1205G>A（p.Arg402Gln）、外显子 5 缺失）。总 C26-神经酰胺及其反式异构体在检测受试患者的ASAH1相关疾病方面均表现出 100% 的敏感性。一名 10 岁女孩具有新的变异 c.1205G>A (p.Arg402Gln)，表现为一种新的 PME 特殊表型，但没有肌肉萎缩。我们扩展了ASAH1相关疾病的表型谱，并验证了生物标志物C26-神经酰胺以支持有症状患者的诊断。