Touro College of Osteopathic Medicine, Middletown, NY, 10940.
Children's Hospital of Philadelphia Research Institute, Philadelphia, PA, 19104.
Ann Clin Transl Neurol. 2021 Nov;8(11):2199-2204. doi: 10.1002/acn3.51464. Epub 2021 Oct 6.
Two siblings presented similarly with congenital hypotonia, lactic acidosis, and failure to thrive. Later in childhood, the brother developed cystinuria and nephrolithiasis whereas the older sister suffered from cystinuria and chronic neurobehavioral disturbances. Biopsied muscle studies demonstrated deficient cytochrome c oxidase activities consistent with a mitochondrial disease. Whole exome sequencing (WES), however, revealed a homozygous 2p21 deletion involving two contiquous genes, SLC3A1 (deletion of exons 2-10) and PREPL (deletion of exons 2-14). The molecular findings were consistent with the hypotonia-cystinuria 2p21 deletion syndrome, presenting similarly in infancy with mitochondrial dysfunction but diverging later in childhood and displaying intrafamilial phenotypic variability.
一对兄妹均表现为先天性肌张力低下、乳酸性酸中毒和生长发育迟缓。在儿童后期，哥哥（弟）发展为胱氨酸尿症和肾结石，而姐姐（妹）则患有胱氨酸尿症和慢性神经行为障碍。肌肉活检研究显示细胞色素 c 氧化酶活性缺陷，符合线粒体疾病。全外显子组测序（WES）显示，2p21 纯合缺失涉及两个连续基因，SLC3A1（外显子 2-10 缺失）和 PREPL（外显子 2-14 缺失）。分子发现与张力低下-胱氨酸尿症 2p21 缺失综合征一致，在婴儿期均表现为线粒体功能障碍，但在儿童后期表现出不同，表现出家族内表型变异性。
