目的:探讨3例晚发型多酰基辅酶A脱氢酶缺乏症(MADDⅢ型)患儿的临床特点及遗传变异。
方法:回顾性分析2020年3月至2022年3月郑州大学附属儿童医院收治的3例晚发性MADD患儿的临床资料。所有儿童均接受全外显子组测序(WES),和候选变体通过Sanger测序进行验证。所有患儿均接受改善代谢治疗,随访1~3年。
结果:儿童包括2名男性和1名女性,年龄由2个月至11岁零7个月。儿童1有间歇性呕吐,孩子2有下肢无力,而儿童3除了异常新生儿筛查外没有任何症状。三个孩子的串联质谱显示多个酰基肉碱升高,中链和长链。儿童1和2通过尿液气相色谱-质谱(GC-MS)分析显示戊二酸和多种二羧酸增加。发现所有儿童都带有ETFDH基因的复合杂合变体,包括父系c.1211T>C(p。M404T)和儿童1的母体c.488-22T>G变体,父系c.1717C>T(p。Q573X)和母体c.250G>A(p。A84T)在儿童2中变异,父系c.12851G>A,母系c.629A>G(p。S210N)子3中的变体。至于治疗,给予大剂量维生素B2、左卡尼汀和辅酶Q10以改善代谢,除了低脂肪,低蛋白质和高碳水化合物饮食。所有患儿在随访期间病情稳定,生长发育正常。
结论:ETFDH基因的复合杂合变体可能是肌肉无力的基础,及时呕吐,升高短,中等,和长链酰基肉碱,3例Ⅲ型MADD患儿戊二酸和各种二羧酸水平升高。
OBJECTIVE: To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ).
METHODS: Clinical data of three children diagnosed with late-onset MADD at the Children\'s Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years.
RESULTS: The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c.1211T>C (p.M404T) and a maternal c.488-22T>G variant in child 1, a paternal c.1717C>T (p.Q573X) and a maternal c.250G>A (p.A84T) variant in child 2, and a paternal c.1285+1G>A and maternal c.629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up.
CONCLUSIONS: The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.