Fatal neonatal respiratory failure in an infant with congenital hypothyroidism due to haploinsufficiency of the NKX2-1 gene: alteration of pulmonary surfactant homeostasis
Fatal neonatal respiratory failure in an infant with congenital hypothyroidism due to haploinsufficiency of the NKX2-1 gene: alteration of pulmonary surfactant homeostasis
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DOI：
10.1136/adc.2009.180448
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发表时间：
2011-11-01
影响因子：
4.4
通讯作者：
Holzinger, Andreas
中科院分区：
文献类型：
--
作者：
Kleinlein, Barbara;Griese, Matthias;Holzinger, Andreas
编码甲状腺转录因子-1的NKX 2 -1基因的缺陷会导致脑-甲状腺-肺综合征（MIM 610978），其特征是良性遗传性舞蹈病、先天性甲状腺功能减退症和呼吸道疾病。一个长期婴儿的情况下，轻度原发性先天性甲状腺功能减退症和新生儿持续性呼吸衰竭与致命的结果，在10个月的年龄，尽管持续的辅助治疗的支持。排除了已知干扰表面活性蛋白和脂质稳态的基因（SFTPB、SFTPC、ABCA 3）的先天性缺陷。甲状腺功能减退促使NKX 2 -1的测序，其显示杂合的29 bp缺失（c.278_306del29）破坏了受影响的等位基因。支气管肺泡灌洗液的分析表明，与SP-B相关的表面活性蛋白C（SP-C）含量异常低，表面活性磷脂水平低，表明NKX 2 -1单倍不足导致SP和脂质稳态紊乱。NKX 2 -1单倍不足可能导致新生儿由于肺表面活性物质稳态的破坏而导致致命的呼吸衰竭。NKX 2 -1基因分析应考虑在调查新生儿不可逆的呼吸功能不全。
Defects of the NKX2-1 gene, encoding thyroid transcription factor-1, cause brain-thyroid-lung syndrome (MIM 610978), characterised by benign hereditary chorea, congenital hypothyroidism and respiratory disease. The case of a term infant with mild primary congenital hypothyroidism and neonatal persistent respiratory failure with fatal outcome at 10 months of age despite continuous ventilatory support is described. Congenital defects of genes known to disturb surfactant protein and lipid homeostasis (SFTPB, SFTPC, ABCA3) were excluded. Hypothyroidism prompted sequencing of NKX2-1, which revealed a heterozygous 29 bp deletion (c.278_306del29) disrupting the affected allele. Analysis of bronchoalveolar lavage fluid demonstrated an abnormally low amount of surfactant protein C (SP-C) in relation to SP-B, and low levels of surfactant phospholipids, indicating disturbance of SP and lipid homeostasis as a consequence of NKX2-1 haploinsufficiency. NKX2-1 haploinsufficiency may lead to lethal respiratory failure of the newborn due to disruption of pulmonary surfactant homeostasis. NKX2-1 gene analysis should be considered when investigating irreversible respiratory insufficiency of the newborn.