To expand the genetic spectrum of hereditary spastic paraparesis by a treatable condition and to evaluate the therapeutic effects of biotin supplementation in an adult patient with biotinidase deficiency (BD).

We performed exome sequencing (ES) in a patient with the clinical diagnosis of complex hereditary spastic paraparesis. The patient was examined neurologically, including functional rating scales. We performed ophthalmologic examinations and metabolic testing.

A 41-year-old patient presented with slowly progressive lower limb spasticity combined with optic atrophy. He was clinically diagnosed with complex hereditary spastic paraparesis. The initial panel diagnostics did not reveal the disease-causing variant; therefore, ES was performed. ES revealed biallelic pathogenic variants in the BTD gene leading to the genetic diagnosis of BD. BD is an autosomal recessive metabolic disorder causing a broad spectrum of neurologic symptoms, optic atrophy, and dermatologic abnormalities. When treatment is initiated in time, symptoms can be prevented or reversed by biotin supplementation. After diagnosis in our patient, biotin supplementation was started. One year after the onset of therapy, symptoms remained stable with slight improvement of sensory deficits.

These findings expand the genetic spectrum of the clinical diagnosis of complex hereditary spastic paraparesis by a treatable disease. Today, most children with BD should have been identified via newborn screening to start biotin supplementation before the onset of symptoms. However, adult patients and those born in countries without newborn screening programs for BD are at risk of being missed. Therapeutic success depends on early diagnosis and presymptomatic treatment.

通过可治疗的病症扩大遗传性痉挛性截瘫的遗传谱，并评估生物素补充剂对患有生物素酶缺乏症 (BD) 的成年患者的治疗效果。

我们对临床诊断为复杂遗传性痉挛性截瘫的患者进行了外显子组测序 (ES)。对患者进行了神经学检查，包括功能评定量表。我们进行了眼科检查和代谢测试。

一名 41 岁的患者出现缓慢进展的下肢痉挛并伴有视神经萎缩。他被临床诊断为复杂的遗传性痉挛性截瘫。最初的小组诊断没有发现致病变异；因此，进行了ES。ES 揭示了导致 BD 基因诊断的BTD基因中的双等位基因致病变异。BD 是一种常染色体隐性遗传代谢疾病，可导致广泛的神经系统症状、视神经萎缩和皮肤病学异常。当及时开始治疗时，可以通过补充生物素来预防或逆转症状。在我们的患者诊断后，开始补充生物素。治疗开始一年后，症状保持稳定，感觉障碍略有改善。

这些发现扩大了可治疗疾病对复杂遗传性痉挛性下肢轻瘫的临床诊断的遗传谱。今天，大多数患有 BD 的儿童应该已经通过新生儿筛查确定，以便在症状出现之前开始补充生物素。然而，成年患者和出生在没有 BD 新生儿筛查计划的国家的患者有被遗漏的风险。治疗成功取决于早期诊断和症状前治疗。