Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India.
University Children's Hospital Zurich and Children's Research Centre, Steinwiesstr 75, CH-8032, Zurich, Switzerland.
Orphanet J Rare Dis. 2018 Oct 1;13(1):174. doi: 10.1186/s13023-018-0908-1.
Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile.
We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G > A (p.Arg157His) and c.1168G > A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis.
We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies.
尿素循环障碍（UCD）是一种遗传性代谢疾病，表现为高血氨症，并导致婴儿和儿童的死亡率和发病率显著增加。由于缺乏对临床和分子特征的全面研究，这些疾病在印度人群中报道较少。
我们报告了印度两个主要代谢中心的数据，包括 123 例各种 UCD 病例。其中大多数（72/123，58%）在新生儿期（出生后 30 天内）出现，其中 88%（72/82）在出生后 7 天内出现（经典表现），死亡率较高（64/72，88%）。瓜氨酸血症 1 型是最常见的 UCD，见于 61/123 例患者。鸟氨酸氨甲酰转移酶（OTC）缺乏症是第二常见的，见于 24 例。精氨酸琥珀酸尿症诊断为 20 例。还观察到精氨酸酶、N-乙酰谷氨酸合酶、氨甲酰磷酸合成酶、Citrin 和赖氨酸尿蛋白不耐受症的缺乏。分子遗传学分析显示 ASS1 基因有两个常见突变：c.470G>A（p.Arg157His）和 c.1168G>A（p.Gly390Arg）（36 例接受检测的患者中）。此外，还观察到 ASL 基因的少数复发性点突变和整个 OTC 基因缺失。在所研究的各种基因中总共观察到 24 个新突变。我们观察到总体预后不良，总死亡率为 63%（70/110 例有已知随访），幸存者中残疾率为 70%（28/40）。在 25 个家庭的 30 例妊娠中进行了产前诊断，包括一例植入前遗传学诊断。
我们报告了印度 UCD 的发生情况，其谱可能与世界其他地区不同。瓜氨酸血症 1 型是队列中最常见的 UCD。提高临床医生的认识将通过早期诊断和及时治疗改善结局。对先证者进行基因诊断将使随后的妊娠能够进行产前/植入前诊断。
Zotero 插件