McGowan Rachel, Yano Shoji
Genetics Division, Pediatrics, Los Angeles General Hospital, University of Southern California, Los Angeles, CA, USA.
Mol Genet Metab Rep. 2024 Aug 31;41:101138. doi: 10.1016/j.ymgmr.2024.101138. eCollection 2024 Dec.
3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency is an autosomal recessive disorder of leucine metabolism. Since 3-MCC deficiency is thought to be a benign condition, a few newborn screening programs discontinued to screen this condition. We report a case of a 24-year-old previously healthy male patient who developed generalized rhabdomyolysis, weakness, respiratory and renal failure, acute pancreatitis, hyperammonemia, and altered consciousness after strenuous exercise. Diagnosis of 3-MCC was made based on increased plasma C5OH carnitine, urine 3-methylcrotonylglycine, and 3-hydroxyisovalerate, and later whole genome sequencing study confirmed the diagnosis. Low plasma carnitine and high creatine kinase (CK) levels were again noted after two months of poor compliance with carnitine therapy. Since 3-MCC deficiency is often incidentally diagnosed in asymptomatic mothers through positive newborn screening in the newborns and most positive newborn screening cases have benign clinical outcomes, 3-MCC deficiency has been considered a benign condition. Observation of a life-threatening episode triggered by strenuous exercise and recurrent occurrence of low carnitine and high CK without carnitine supplementation may support 3-MCC deficiency to be the condition covered by the newborn screen since carnitine supplementation likely prevents an episode that can be life-threatening. Asymptomatic adults with 3-MCC deficiency may benefit from periodic evaluation of plasma carnitine levels.
3-甲基巴豆酰辅酶A羧化酶(3-MCC)缺乏症是一种常染色体隐性遗传的亮氨酸代谢紊乱疾病。由于3-MCC缺乏症曾被认为是一种良性病症,一些新生儿筛查项目已停止对该病症进行筛查。我们报告了一例24岁的既往健康男性患者,该患者在剧烈运动后出现了全身性横纹肌溶解、肌无力、呼吸及肾衰竭、急性胰腺炎、高氨血症以及意识改变。基于血浆C5OH肉碱、尿3-甲基巴豆酰甘氨酸和3-羟基异戊酸水平升高做出了3-MCC缺乏症的诊断,随后全基因组测序研究证实了该诊断。在肉碱治疗依从性差两个月后,再次发现血浆肉碱水平低和肌酸激酶(CK)水平高。由于3-MCC缺乏症常通过新生儿的新生儿筛查呈阳性而在无症状母亲中被偶然诊断出来,且大多数新生儿筛查呈阳性的病例临床结局良好,因此3-MCC缺乏症一直被认为是一种良性病症。观察到剧烈运动引发的危及生命的发作以及在未补充肉碱的情况下反复出现低肉碱和高CK水平,可能支持将3-MCC缺乏症纳入新生儿筛查范围,因为补充肉碱可能预防危及生命的发作。无症状的3-MCC缺乏症成年人可能会从定期评估血浆肉碱水平中受益。