PDF(Pubmed)
Abstract：
Biotinidase (BTD) deficiency (OMIM 253260) is an autosomal recessively inherited metabolic disorder resulting from deficient activity of the BTD enzyme, which can cleave and release biotin from a variety of biotin-dependent carboxylases, and is therefore recognized as a tool to recycle biotin. Being a condition caused by variations on BTD gene with a consequence of free biotin shortage, BTD deficiency may impair the activity of biotin-dependent carboxylases, and thus bring about a buildup of potentially toxic compounds in the body, primarily 3-hydroxyisovaleryl-carnitine in plasma as well as 3-hydroxyisovaleric acid in urine. The phenotype of BTD deficiency may vary dramatically, from asymptomatic adults to severe neurological anomalies, even death in infancy. In the present study, we reported on a 5-month-old boy, whose parents sought for medical consultation in our clinic for their son due to his loss of consciousness, repeated tetany, and motor retardation. Detailed clinical features included severe psychomotor retardation, hypotonia, as well as failure to thrive. The brain MRI at 12 months showed cerebellar hypoplasia and multiple foci of leukodystrophy. The result of antiepileptic therapy was not satisfying. During hospitalization, BTD deficiency was suggested by elevated concentration of 3-hydroxyisovaleryl-carnitine in the blood spots and 3-hydroxyisovaleric acid in the urine. The child was then diagnosed with profound BTD deficiency based on the above findings and low BTD enzyme activity. Subsequent mutational analysis revealed a novel homozygous variant, c.637_637delC (p.H213Tfs*51) in exon 4 of BTD gene in the proband, which was recognized as a further support to the diagnosis. Therefore, biotin treatment was started immediately, eventually with satisfactory outcomes achieved in terms of prevention of epileptic seizure, performance in deep tendon reflexes, and improvement of muscular hypotonia, but unfortunately, the therapy failed to show any evident effects on poor feeding and intellectual disability. This painful lesson suggests that newborn screening for inherited metabolic diseases is essential for early identification and treatment, which should have been performed in this case to avoid this tragedy.
摘要：
生物素酶（BTD）缺乏症（OMIM253260）是一种常染色体隐性遗传代谢紊乱，由BTD酶活性不足引起，可以从多种依赖生物素的羧化酶中切割和释放生物素，因此被认为是回收生物素的工具。是由BTD基因变异引起的疾病，是游离生物素短缺的结果，BTD缺乏可能会损害生物素依赖性羧化酶的活性，从而导致体内潜在有毒化合物的积聚，血浆中主要是3-羟基异戊酰基肉碱，尿液中主要是3-羟基异戊酸。BTD缺乏症的表型可能差异很大，从无症状的成年人到严重的神经系统异常，甚至在婴儿期死亡。在本研究中,我们报道了一个5个月大的男孩,由于儿子失去意识，其父母在我们的诊所为他寻求医疗咨询，反复手提，和运动迟缓。详细的临床特征包括严重的精神运动发育迟缓，低张力,以及未能茁壮成长。12个月时的脑MRI显示小脑发育不全和脑白质营养不良的多个病灶。抗癫痫治疗的结果不令人满意。住院期间,血液斑点中3-羟基异戊酰基肉碱和尿液中3-羟基异戊酸的浓度升高提示BTD缺乏症。然后基于上述发现和低BTD酶活性，该儿童被诊断为严重的BTD缺乏症。随后的突变分析揭示了一个新的纯合变体，c.637_637delC（p。H213Tfs*51)在先证者的BTD基因外显子4中，这被认为是对诊断的进一步支持。因此,生物素治疗立即开始，最终在预防癫痫发作方面取得了令人满意的结果，在深肌腱反射中的表现，和改善肌肉张力减退，但不幸的是,该疗法对喂养不良和智力障碍没有任何明显的影响。这一惨痛的教训表明，新生儿筛查遗传代谢性疾病对于早期识别和治疗至关重要。在这种情况下应该执行以避免这场悲剧。
