PDF(Pubmed)
Abstract：
3-methylcrotonyl-CoA carboxylase deficiency (3MCCD) is a hereditary disorder of leucine catabolism caused by pathogenetic variants in the MCCC1 or MCCC2 genes. Typically diagnosed through newborn screening (NBS), 3MCCD is characterized by elevation of 3-hydroxyisovalerylcarnitine (C5OH) in blood as well as increased excretion of 3-methylcrotonylglycine (3-MCG) in urine. While most diagnosed children remain asymptomatic, data on adults are scarce. To date, only 39 molecularly confirmed adult individuals have been reported, all being mothers diagnosed subsequent to their child NBS results. Herein, we present a 36-year-old asymptomatic man who was incidentally diagnosed with 3MCCD following his son NBS recall. Molecular analysis revealed compound heterozygosity for two pathogenic variants in the MCCC1 gene. This is the first molecularly confirmed adult man with 3MCCD reported. This case highlights the need for additional longitudinal follow-up data on individuals with 3MCCD to clarify the clinical significance of this condition and guide clinical practice, including NBS strategy.
摘要：
3-甲基巴豆酰辅酶A羧化酶缺乏症（3MCCD）是由MCCC1或MCCC2基因的致病变体引起的亮氨酸分解代谢的遗传性疾病。通常通过新生儿筛查（NBS）诊断，3MCCD的特征在于血液中3-羟基异戊酰基肉碱（C5OH）的升高以及尿液中3-甲基巴豆酰基甘氨酸（3-MCG）的排泄增加。虽然大多数被诊断的儿童仍然无症状，关于成年人的数据很少。迄今为止,只有39个分子确认的成年人被报道，所有的母亲都是在孩子NBS结果后被诊断出来的。在这里，我们介绍了一名36岁无症状男性,他在儿子NBS召回后偶然被诊断为3MCCD.分子分析揭示了MCCC1基因中两个致病变体的复合杂合性。这是首次报道的3MCCD分子证实的成年男子。该病例强调需要对患有3MCCD的个体进行额外的纵向随访数据，以阐明这种情况的临床意义并指导临床实践。包括NBS战略。
