Introduction

Biotinidase deficiency (BD) is an autosomal recessively inherited disorder characterized by developmental delay, seizures, hypotonia, ataxia, skin rash/eczema, alopecia, conjunctivitis/visual problem/optic atrophy and metabolic acidosis. Delayed diagnosis may lead to irreversible neurological damage.

Methodology

Clinically suspected patients were screened for biotinidase level by a fluorometry method. Profound BD patients were confirmed by mutation analysis of BTD gene.

Results

9 patients had biotinidase activity of less than 77 U. 3 patients (33%) had profound BD while 6 patients (67%) had partial BD. Compound heterozygous mutations were detected at c.98_104delinsTCC p.(Cys33Phefs*36) in Exon 2 and c.833T>C p.(Leu278Pro) in Exon 4 in two patients and a homozygous mutation at c.98_104delinsTCC p.(Cys33Phefs*36) in Exon 2 in another patient.

Conclusion

Correct diagnosis lead to early treatment and accurate management of patient. Biochemical screening of BD in symptomatic child is prerequisite to determine enzyme status however molecular confirmation is vital in differentiating individuals with profound biotinidase deficiency from partial biotinidase deficiency and also individuals' carriers.

中文翻译：

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马来西亚人口中生物素酶缺乏症的临床、生化和突变发现。

介绍

生物素酶缺乏症 (BD) 是一种常染色体隐性遗传疾病，其特征是发育迟缓、癫痫发作、肌张力减退、共济失调、皮疹/湿疹、脱发、结膜炎/视力问题/视神经萎缩和代谢性酸中毒。延误诊断可能导致不可逆的神经损伤。

方法

通过荧光测定法筛查临床疑似患者的生物素酶水平。BTD基因突变分析证实有严重BD患者。

结果

9 名患者的生物素酶活性低于 77 U。3 名患者 (33%) 患有严重 BD，而 6 名患者 (67%) 患有部分 BD。两名患者在外显子 2 的 c.98_104delinsTCC p.(Cys33Phefs*36) 和外显子 4 的 c.833T>C p.(Leu278Pro) 检测到复合杂合突变，在 c.98_104delinsTCC p.(Cys33Phefs*36) 检测到纯合突变) 在另一名患者的外显子 2 中。

结论

正确的诊断导致早期治疗和患者的准确管理。对有症状的儿童进行 BD 的生化筛查是确定酶状态的先决条件，但分子确认对于区分具有严重生物素酶缺乏症的个体与部分生物素酶缺乏症以及个体携带者至关重要。