PDF(Pubmed)
Abstract：
BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) or glutaric aciduria type II is an extremely rare autosomal recessive inborn error of fatty acid beta oxidation and branched-chain amino acids, secondary to mutations in the genes encoding the electron transfer flavoproteins A and B (ETFs; ETFA or ETFB) or ETF dehydrogenase (ETFDH). The clinical manifestation of MADD are heterogeneous, from severe neonatal forms to mild late-onset forms.
METHODS: We report the case of a preterm newborn who died a few days after birth for a severe picture of untreatable metabolic acidosis. The diagnosis of neonatal onset MADD was suggested on the basis of clinical features displaying congenital abnormalities and confirmed by the results of expanded newborn screening, which arrived the day the newborn died. Molecular genetic test revealed a homozygous indel variant c.606 + 1 _606 + 2insT in the ETFDH gene, localized in a canonical splite site. This variant, segregated from the two heterozygous parents, is not present in the general population frequency database and has never been reported in the literature.
CONCLUSIONS: Recently introduced Expanded Newborn Screening is very important for a timely diagnosis of Inherited Metabolic Disorders like MADD. In some cases which are the most severe, diagnosis may arrive after symptoms are already present or may be the neonate already died. This stress the importance of collecting all possible samples to give parents a proper diagnosis and a genetic counselling for future pregnacies.
METHODS: We report the case of a preterm newborn who died a few days after birth for a severe picture of untreatable metabolic acidosis. The diagnosis of neonatal onset MADD was suggested on the basis of clinical features displaying congenital abnormalities and confirmed by the results of expanded newborn screening, which arrived the day the newborn died. Molecular genetic test revealed a homozygous indel variant c.606 + 1 _606 + 2insT in the ETFDH gene, localized in a canonical splite site. This variant, segregated from the two heterozygous parents, is not present in the general population frequency database and has never been reported in the literature.
CONCLUSIONS: Recently introduced Expanded Newborn Screening is very important for a timely diagnosis of Inherited Metabolic Disorders like MADD. In some cases which are the most severe, diagnosis may arrive after symptoms are already present or may be the neonate already died. This stress the importance of collecting all possible samples to give parents a proper diagnosis and a genetic counselling for future pregnacies.
摘要：
背景：多重酰基辅酶A脱氢酶缺乏症（MADD）或戊二酸尿症II型是一种极为罕见的常染色体隐性遗传性先天性脂肪酸β氧化和支链氨基酸错误，继发于编码电子转移黄素蛋白A和B（ETF；ETFA或ETFB）或ETF脱氢酶（ETFDH）的基因中的突变。MADD的临床表现是异质性的，从严重的新生儿形式到轻度的迟发性形式。
方法：我们报告一例早产新生儿在出生后几天因严重的代谢性酸中毒而死亡。根据显示先天性异常的临床特征并经扩大新生儿筛查结果证实，建议诊断为新生儿发病MADD。这是在新生儿死亡的那天。分子遗传学检测揭示了ETFDH基因中的纯合indel变异c.606+1_606+2insT，位于典型的拼接位点。这个变种,与两个杂合亲本分离，在一般人群频率数据库中不存在，也从未在文献中报道过。
结论：最近推出的扩大新生儿筛查对于像MADD这样的遗传性代谢紊乱的及时诊断非常重要。在一些最严重的情况下，诊断可能在症状已经出现或可能是新生儿已经死亡后才出现。这强调了收集所有可能的样本的重要性，以便为父母提供适当的诊断和对未来怀孕的遗传咨询。
方法：我们报告一例早产新生儿在出生后几天因严重的代谢性酸中毒而死亡。根据显示先天性异常的临床特征并经扩大新生儿筛查结果证实，建议诊断为新生儿发病MADD。这是在新生儿死亡的那天。分子遗传学检测揭示了ETFDH基因中的纯合indel变异c.606+1_606+2insT，位于典型的拼接位点。这个变种,与两个杂合亲本分离，在一般人群频率数据库中不存在，也从未在文献中报道过。
结论：最近推出的扩大新生儿筛查对于像MADD这样的遗传性代谢紊乱的及时诊断非常重要。在一些最严重的情况下，诊断可能在症状已经出现或可能是新生儿已经死亡后才出现。这强调了收集所有可能的样本的重要性，以便为父母提供适当的诊断和对未来怀孕的遗传咨询。
