背景:本研究旨在描述临床,生物化学,全羧化酶合成酶(HLCS)缺乏症患者的分子特征,并研究HCLS缺乏症的突变谱及其与表型的潜在相关性。
方法:共纳入2006年至2021年的28例HLCS缺乏症患者。从病历中回顾性审查临床和实验室数据。
结果:在28例患者中,六名患者接受了新生儿筛查,其中只有一个被错过了。因此,23例患者因疾病发作而被诊断。在所有的病人中,24例出现不同程度的皮疹等症状,呕吐,癫痫发作,和困倦,而如今只有4例无症状。血液和丙酮酸中3-羟基异戊酰基肉碱(C5-OH)的浓度,3-羟基丙酸酯,甲基柠檬酸,3-羟基戊酸,在受影响的个体中,尿液中的3-甲基巴豆酰基甘氨酸大大增加。及时补充生物素后,临床和生化症状均得到显著缓解,随访中几乎所有患者的智力和体质均正常.DNA测序揭示了患者HLCS基因中的12种已知变体和6种新型变体。其中,c.1522C>T的变体是最常见的。
结论:我们的发现扩展了中国人群中HLCS缺乏症的表型和基因型,并表明及时的生物素治疗,HLCS缺乏症患者死亡率低,预后乐观.新生儿筛查对早期诊断至关重要,治疗,和长期结果。
This study aimed to describe the clinical, biochemical, and molecular characteristics of Chinese patients with holocarboxylase synthetase (HLCS) deficiency, and to investigate the mutation spectrum of HCLS deficiency as well as their potential correlation with phenotype.
A total of 28 patients with HLCS deficiency were enrolled between 2006 and 2021. Clinical and laboratory data were reviewed retrospectively from medical records.
Among the 28 patients, six patients underwent newborn screening, of which only one was missed. Therefore, 23 patients were diagnosed because of disease onset. Among all the patients, 24 showed varying degrees of symptoms such as rash, vomiting, seizures, and drowsiness, while only four cases remained asymptomatic nowadays. The concentration of 3-hydroxyisovalerylcarnitine (C5-OH) in blood and pyruvate, 3-hydroxypropionate, methylcitric acid, 3-hydroxyvaleric acid, 3-methylcrotonylglycine in urine were increased greatly among affected individuals. After prompt supplement of biotin, both the clinical and biochemical symptoms were dramatically resolved and nearly all patients developed normal intelligence and physique on follow-up. DNA sequencing revealed 12 known and 6 novel variants in the HLCS gene of patients. Among them, the variant of c.1522C > T was the most common.
Our findings expanded the spectrum of phenotypes and genotypes for HLCS deficiency in Chinese populations and suggested that with timely biotin therapy, patients with HLCS deficiency showed low mortality and optimistic prognosis. Newborn screening is crucial for early diagnosis, treatment, and long-term outcomes.