Kasapkara Çiğdem Seher, Tümer Leyla, Ezgü Fatih Suheyl, Küçükçongar Aynur, Hasanoğlu Alev
Department of Pediatric Metabolism and Nutrition, Gazi University Hospital , Ankara , Turkey.
Ren Fail. 2014 Jul;36(6):953-4. doi: 10.3109/0886022X.2014.900422. Epub 2014 Mar 24.
GRACILE syndrome is a rare autosomal recessive disease characterized by fetal growth retardation, Fanconi type aminoaciduria, cholestasis, iron overload, profound lactic acidosis, and early death. It is caused by homozygosity for a missense mutation in the BCS1L gene. The BCS1L gene encodes a chaperone responsible for assembly of respiratory chain complex III. Here we report that a homozygous mutation c.296C > T (p.P99L), in the first exon of BCS1L gene found in an affected 2-month-old boy of asymptomatic consanguineous parents results in GRACILE syndrome. This genotype is associated with a severe clinical presentation. So far no available treatments have changed the fatal course of the disease, and the metabolic disturbance responsible is still not clearly identified. Therefore, providing prenatal diagnosis in families with previous affected infants is of major importance. Mitochondrial disorders are an extremely heterogeneous group of diseases sharing, in common, the fact that they all ultimately impair the function of the mitochondrial respiratory chain. A clinical picture with fetal growth restriction, postnatal lactacidosis, aminoaciduria, hypoglycemia, coagulopathy, elevated liver enzymes, and cholestasis should direct investigations on mitochondrial disorder.
GRACILE综合征是一种罕见的常染色体隐性疾病，其特征为胎儿生长迟缓、范科尼型氨基酸尿症、胆汁淤积、铁过载、严重乳酸酸中毒及早期死亡。它由BCS1L基因中的一个错义突变纯合子所致。BCS1L基因编码一种伴侣蛋白，负责呼吸链复合物III的组装。在此我们报告，在一名无症状近亲父母所生的2个月大患病男婴中发现的BCS1L基因第一外显子中的纯合突变c.296C>T（p.P99L）导致了GRACILE综合征。这种基因型与严重的临床表现相关。到目前为止，尚无有效的治疗方法改变该疾病的致命进程，且导致疾病的代谢紊乱仍未明确。因此，对有患病婴儿史的家庭进行产前诊断至关重要。线粒体疾病是一组极其异质性的疾病，它们的共同之处在于最终都会损害线粒体呼吸链的功能。具有胎儿生长受限、产后乳酸酸中毒、氨基酸尿症、低血糖、凝血障碍、肝酶升高及胆汁淤积的临床表现应指导对线粒体疾病的调查。
