目的:在本研究中,我们旨在基于重复的生物素酶酶测量来评估生物素酶酶缺乏症患者的基因型-表型关系.
方法:患者的医院档案信息,酶缺乏进行回顾性评估,并分析了首次和重复酶活性评估后的BTD基因突变分析结果与生物素酶活性之间的关系。
结果:纳入了一百一十例患者。在第一次酶评估中,在15例(13.6%)中发现了严重的生物素酶缺乏症,63例(57.3%)的部分生物素酶缺乏,32例(29.1%)患者存在杂合子生物素酶缺乏症。BTD遗传分析显示42(38.2%)纯合,42(38.2%)杂合,和26个(23.6%)复合杂合变体。最常见的纯合变体,p.Asp444His,通过130次重复酶测量进行评估,并且在55.4%的病例中与部分生物素酶缺乏一致,杂合子生物素酶缺乏在43.8%的病例,1例(0.8%)严重缺乏生物素酶。17例患者在随访期间出现临床症状,其中70.6%与神经发育有关。在出现症状的患者中,最常见的变异是纯合p.Asp444His(29.4%)。
结论:这是迄今为止第一项通过重复测量生物素酶活性来评估生物素酶缺乏症患者基因型-表型关系的研究。研究表明,单独的生物素酶活性不足以诊断生物素酶缺乏或评估疾病的严重程度。因为遗传研究也需要确定诊断生物素酶酶缺乏症。
OBJECTIVE: In the present study, we aimed to evaluate the genotype-phenotype relation in patients with biotinidase enzyme deficiency based on repeated biotinidase enzyme measurements.
METHODS: The hospital file information of patients with biotinidase, enzyme deficiency was assessed retrospectively, and the relationship between the BTD gene mutations analysis results and biotinidase enzyme activity following the first and repeated enzyme activity assessments was analyzed.
RESULTS: One-hundred-ten patients were included. In the first enzyme evaluation, profound biotinidase enzyme deficiency was identified in 15 (13.6 %), partial biotinidase enzyme deficiency in 63 (57.3 %), and heterozygous biotinidase enzyme deficiency in 32 (29.1 %) of the patients. The BTD genetic analysis revealed 42 (38.2 %) homozygous, 42 (38.2 %) heterozygous, and 26 (23.6 %) compound heterozygous variants. The most common homozygous variant, p.Asp444His, was evaluated with 130 repeated enzyme measurements and was consistent with a partial biotinidase enzyme deficiency in 55.4 % of cases, heterozygous biotinidase enzyme deficiency in 43.8 % of cases, and profound biotinidase enzyme deficiency in one (0.8 %) case. Clinical symptoms developed in 17 patients during follow-up, of which 70.6 % were related to neurodevelopment. The most common variant was homozygous p.Asp444His (29.4 %) among the patients who developed symptoms.
CONCLUSIONS: This is the first study to date to evaluate the genotype-phenotype relationship in patients with biotinidase deficiency through repeated measurements of biotinidase enzyme activity. The study reveals that biotinidase enzyme activity alone is inadequate for diagnosing biotinidase enzyme deficiency or evaluating disease severity, as genetic investigations are also required for a definitive diagnosis of biotinidase enzyme deficiency.