Newborn screening for ornithine transcarbamylase deficiency in Zhejiang Province and the follow-up analysis
10.3760/cma.j.cn101070-20221102-01246
- VernacularTitle:浙江省新生儿鸟氨酸氨甲酰转移酶缺乏症筛查及随访分析
- Author:
Duo ZHOU
1
;
Rulai YANG
;
Xinwen HUANG
;
Fan TONG
;
Xiaolei HUANG
;
Guling QIAN
;
Xin YANG
;
Jianbin YANG
;
Zhengyan ZHAO
Author Information
1. 浙江大学医学院附属儿童医院遗传与代谢科，国家儿童健康与疾病临床医学研究中心，国家儿童区域医疗中心，杭州 310052
- Keywords:
Ornithine transcarbamylase deficiency;
Urea cycle disorders;
Newborn screening
- From:
Chinese Journal of Applied Clinical Pediatrics
2023;38(1):43-48
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the incidence, clinical characteristics and prognosis of ornithine transcarbamylase deficiency(OCTD) in newborns in Zhejiang Province.Methods:A retrospective research was conducted.A total of 4 261 036 newborns from Department of Genetics and Metabolism, Children′s Hospital, Zhejiang University School of Medicine, between January 2009 and December 2021 were screened for inherited metabolic disorders using tandem mass spectrometry.OCTD was confirmed by urine organic acid and OTC gene analysis.Patients with OTCD received guidance on diet and lifestyle management, and were treated with citrulline and arginine.Long-term follow-up was performed.Their growth and intellectual development were evaluated. Results:A total of 7 patients with OCTD were diagnosed, with an incidence of 1.6/1 million.All patients were males.Two patients had neonatal-onset OCTD, and the other 5 had late-onset OCTD.Symptoms occurred several times in 6 patients, inducing hyperammonemia and hepatic impairment.One patient had no clinical manifestation.One patient died in the neonatal period.Blood citrulline levels were decreased in 7 patients to varying degrees.Uracil levels were increased in 4 patients, and 1 of them was complicated with elevated orotic acid levels.All patients had hemizygote variations in the OTC gene, including 6 missense variations(c.604C>T, c.386G>A, c.779T>C, c.1019C>T, c.594C>G, c.931G>A) and 1 intron variation(c.514-35C>G). Two variants(c.594C>G, c.514-35C>G) were never reported previously. Conclusions:The OTCD incidence by newborn screening is low with 1.6/1 million in Zhejiang province.All patients are males and present hypocitrullinemia.The clinical manifestations of OTCD are highly heterogeneous.The neonatal-onset form is severe and survivors always suffer serious sequelae.The late-onset form is mostly manifested with hyperammonemia and hepatic impairment.There may be association between phenotype and genotype.Two novel OTC variants are identified, which further expands the mutational spectrum.
