Division of Genetic Medicine, University of Lausanne and University Hospital of Lausanne, Lausanne, Switzerland.
Genetic Medicine Division, Geneva University Hospitals, Geneva, Switzerland.
Mol Genet Metab. 2023 Apr;138(4):107560. doi: 10.1016/j.ymgme.2023.107560. Epub 2023 Mar 24.
Biotinidase deficiency (BD) is an autosomal recessively inherited disorder that was first described in 1982. Forty years after its first description, we compiled available clinical data on BD with the aim of generating a more comprehensive picture of this condition.
A systematic search strategy was performed in relevant databases without limits for publication date or languages. We screened 3966 records and included 144 articles reporting individuals with BD and their clinical presentation as well as the outcomes, when available.
This study included 1113 individuals with BD. More than half (51.5%) of these individuals were diagnosed by newborn screening, 43.3% in presence of clinical symptoms and 5.2% due to family screening. We grouped symptomatic individuals into four main clinical presentations: neonatal-onset (<1 month; 7.9%), early childhood-onset (<2 years; 59.2%), juvenile-onset (2-16 years; 25.1%) and adult-onset (>16 years; 7.7%). BD affected five main organ systems: nervous system (67.2%), skin (53.7%), eye (34.4%), auditory (26.9%) and respiratory system (17.8%). Involvement was mainly multisystemic (82.2%) of individuals, whereas isolated system presentation was seen in only 17.2% of individuals. When reported, metabolic acidosis was present in 42.4% of symptomatic individuals and characteristic abnormal organic acid metabolites were found in 57.1%. Biotin treatment led to clinical stability or improvement in 89.2% of individuals. 1.6% of reported individuals with BD died due to non-availability of treatment or late diagnosis.
Newborn screening has had a major positive impact on the outcome of many individuals with BD. However, undiagnosed and non-treated BD remains a health concern. Given the risk of mortality or complications associated with late or missed diagnosis if newborn screening is not available, a trial of biotin should be considered in undiagnosed infants and adults exhibiting suspected clinical signs. Enzymatic activity and/or analysis of genetic variants can readily confirm the diagnosis of BD.
生物素酶缺乏症（BD）是一种常染色体隐性遗传疾病，于 1982 年首次描述。在首次描述 40 年后，我们收集了关于 BD 的现有临床数据，旨在更全面地了解这种疾病。
在相关数据库中进行了系统的搜索策略，没有对发表日期或语言进行限制。我们筛选了 3966 条记录，纳入了 144 篇报告 BD 患者及其临床表现以及结果的文章（如果有的话）。
本研究纳入了 1113 名 BD 患者。其中超过一半（51.5%）通过新生儿筛查诊断，43.3%的患者存在临床症状，5.2%的患者因家族筛查而诊断。我们将有症状的个体分为四种主要临床表现：新生儿发病（<1 个月；7.9%）、早发儿童期发病（<2 岁；59.2%）、青少年发病（2-16 岁；25.1%）和成人发病（>16 岁；7.7%）。BD 影响五个主要的器官系统：神经系统（67.2%）、皮肤（53.7%）、眼睛（34.4%）、听觉（26.9%）和呼吸系统（17.8%）。大多数个体表现为多系统受累（82.2%），而仅 17.2%的个体表现为单一系统受累。报告中，有症状的个体中有 42.4%存在代谢性酸中毒，57.1%的个体发现特征性异常有机酸代谢物。生物素治疗使 89.2%的个体的临床状况稳定或改善。报告中，有 1.6%的 BD 患者因治疗不及时或诊断延迟而死亡。
新生儿筛查对许多 BD 患者的结局产生了重大的积极影响。然而，未确诊和未经治疗的 BD 仍然是一个健康问题。如果新生儿筛查不可用，由于延迟或漏诊相关的死亡或并发症风险，对于表现出可疑临床症状的未确诊婴儿和成人，应考虑试用生物素。酶活性和/或遗传变异分析可快速确认 BD 的诊断。
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