背景:全羧化酶合成酶缺乏症(HLCS缺乏症,OMIM#253270)是一种极其罕见的代谢紊乱,由于生物素循环受损而导致多种羧化酶缺乏。临床表现包括严重代谢性酸中毒,高氨血症,呼吸急促,皮疹,脱发,喂养问题,低张力,发育迟缓,癫痫发作,and,在严重的情况下,死亡。
结果:一名8天大的女性新生儿出现严重的乳酸性酸中毒,需要镇静和机械通气。尽管接受了支持性治疗,没有观察到明显的临床改善,伴有全身性鱼鳞病的发作。可操作代谢紊乱的遗传分析揭示了HLCS的复合杂合变体(NM_000411.8),特别是c。[710T>C(p。Leu237Pro)];[1544G>A(p。Ser515Asn)],提示开始生物素大剂量治疗(10毫克/天)。值得注意的是,在开始生物素给药后的第二天观察到乳酸性酸中毒的显著临床改善,导致机械通气在6天内停止。患者在随访期间情况稳定,表现出正常的生长和发育以及持续稳定的实验室发现,直到18个月大。
结论:我们的案例强调了早期基因检测对患有无法解释的代谢紊乱的新生儿的重要性,以便能够及时诊断和开始治疗。生物素治疗在改善HLCS缺乏症患者的临床状况方面具有显着疗效。导致有利的结果。
BACKGROUND: Holocarboxylase synthetase deficiency (HLCS deficiency, OMIM #253270) is an exceedingly rare metabolic disorder resulting in multiple carboxylase deficiencies owing to impaired biotin cycle. Clinical manifestations include severe metabolic acidosis, hyperammonemia, tachypnea, skin rash, alopecia, feeding problems, hypotonia, developmental delay, seizures, and, in severe cases, death.
RESULTS: An 8-day-old female neonate presented with severe lactic acidosis, necessitating sedation and mechanical ventilation. Despite receiving supportive care, no evident clinical improvement was observed, accompanied by the onset of generalized ichthyosis. Genetic analysis of actionable metabolic disorders revealed compound heterozygous variants of HLCS (NM_000411.8), specifically c.[710T>C (p.Leu237Pro)]; [1544G>A (p.Ser515Asn)], prompting the initiation of biotin mega-dose therapy (10 mg/day). Remarkably, dramatic clinical improvement in lactic acidosis was observed the day after initiating biotin administration, leading to the discontinuation of mechanical ventilation within 6 days. The patient remained in stable condition during follow-up, exhibiting normal growth and development along with consistently stable laboratory findings up to 18 months of age.
CONCLUSIONS: Our case highlights the significance of early genetic testing in neonates with unexplained metabolic disorders to enable timely diagnosis and therapy initiation. Biotin therapy has demonstrated remarkable efficacy in improving the clinical condition of patients with HLCS deficiency, leading to favorable outcomes.