一例携带罕见BTD c.690C>G (p.Phe230Leu)变异的部分性生物素酶缺乏症患者的生化和临床特征：病例报告
Biochemical and Clinical Characterization of a Patient with Partial Biotinidase Deficiency Carrying the Rare BTD c.690C>G (p.Phe230Leu) Variant: A Case Report.
文献信息
| PMID | 42795373 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Daniela Semeraro |
| 作者单位 | Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy. |
| 期刊 | Life (Basel, Switzerland) |
| SCI 分区 | Q1 |
| IF | 3.9 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 耳科 |
中文摘要
背景： 生物素酶缺乏症（BD）是一种常染色体隐性遗传病，其中生物素酶（BTD）完全或部分缺陷，维生素生物素不能回收。已鉴定出超过200种BTD基因致病性变异，导致酶活性完全或部分丧失，并导致深度或部分性BD。尽管基因型-表型相关性尚未完全明确，但某些基因型与深度型BD相关，另一些与部分型BD相关。部分性BD患者大多无症状，但在感染等应激条件下可能出现症状。深度BD患者如果不接受生物素补充治疗，可能出现神经系统问题、听力损失、视觉异常和有机酸尿症。BD被纳入大多数新生儿筛查项目（NBS）。筛查试验依赖于干血斑（DBS）中BTD酶活性的测量，随后进行血浆BTD测定和BTD分子分析作为确认试验。我们描述了一名通过新生儿筛查项目发现的部分性BD男婴。检测到DBS中BTD活性低；BTD分子分析显示先证者为复合杂合子，携带已知的轻度变异c.1270G>C (p.Asp424His)和罕见变异c.690C>G (p.Phe230Leu)，后者先前由我们团队鉴定。在本研究中，我们提供了携带c.690C>G (p.Phe230Leu)变异患者的生化和临床特征，我们的发现支持该变异可能对部分性BD表型有贡献。
英文摘要
Biotinidase deficiency (BD) is an autosomal recessive inherited disorder in which the enzyme biotinidase (BTD) is totally or partially defective and the vitamin biotin is not recycled. More than 200 pathogenic variants in the BTD gene have been identified, causing complete or partial loss of enzyme activity and leading to profound or partial BD. Although the genotype-phenotype correlation is not fully defined, some genotypes are associated with profound forms and others with partial forms of BD. The patients with partial BD are mostly asymptomatic but symptoms may appear during stressful conditions such as infections. The patients with profound BD may present neurological problems, hearing loss, visual abnormalities, and organic aciduria, if not treated with biotin supplementation. BD is included in most newborn screening programs (NBS). Screening test relies on measurement of BTD enzyme activity in dried blood spot (DBS), followed by a plasma BTD assay and BTD molecular analysis as confirmatory test. We describe a male newborn with partial BD identified through the newborn screening program. Low BTD activity on DBS was detected; BTD molecular analysis showed the proband to be compound heterozygous for the c.1270G>C (p.Asp424His) mild known variant, and for the rare variant c.690C>G (p.Phe230Leu) previously identified by our group. In this study, we provide the biochemical and clinical characterization of a patient carrying the c.690C>G (p.Phe230Leu) variant, and our findings support a possible contribution of this variant to the partial BD phenotype.