Long-term follow-up of children with carbamoyl phosphate synthase 1 deficiency detectedin newborn screening.

Abstract

OBJECTIVES:

To investigate the incidence, genotype-phenotype characteristics and long-term prognosis of neonatal carbamoyl phosphate synthase 1 (CPS1) deficiency among children through newborn screening in Zhejiang province.

METHODS:

The clinical and follow-up data of children with CPS1 deficiency detected through neonatal screening and confirmedby tandem mass spectrometry and genetic testing in Zhejiang Province Newborn Disease Screening Center from September 2013 to August 2023 were retrospectively analyzed.

RESULTS:

A total of 4 056 755 newborns were screened during September 2013 to August 2023 in Zhejiang province, and 6 cases of CPS1 deficiency were diagnosed through phenotypic and genetic testing. Ten different mutations ofCPS1 genewere identified in genetic testing, including 2 known pathogenic mutations (c.2359C>T, c.1549+1G>T) and 8 unreported mutations (c.3405-1G>T, c.2372C>T, c.1436C>T, c.2228T>C, c.2441G>A, c.3031G>A, c.3075T>C and c.390-403del). All affected infants had decreased citrulline levels (2.72-6.21 μmol/L),and varying degrees of elevated blood ammonia. Following diagnosis, the patients received restricted natural protein intake (special formula), ammonia scavenger and supportive therapy. They were followed up for a period ranging from 9 months to 10 years. Three patients experienced hyperammonemia, and 1 patient each had attention deficit hyperactivity disorder (ADHD),transient facial twitching and increased muscle tone. One patient died, while the other five surviving patients had normal scores of the Ages &Stages Questionnaires (ASQ) and GriffithsDevelopment Scales up to the present time; 4 cases had combined height or weight lag and 1 case was normal in height and weight.

CONCLUSIONS:

The estimated incidence of CPS1deficiency in Zhejiang province is approximately 1 in 680000. The common biochemical changes include low citrulline levels and hyperammonemia. Most mutations identified were specific to individual families, and no hotspot mutations have been found. Early diagnosis through newborn screening and following standardized treatment can significantly improve the prognosis of patients.

• Authors: Zhanming Zhang, Fan Tong, Chi Chen, Ting Zhang, Guling Qian, Xin Yang, Xinwen Huang, Rulai Yang, Zhengyan Zhao
• Journal: Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences (Zhejiang Da Xue Xue Bao Yi Xue Ban) Pg. 1-6 (Nov 14 2023) ISSN: 1008-9292 [Print] China
• Vernacular Title: 新生儿筛查发现的氨甲酰磷酸合成酶1缺乏症患儿长期随访研究.
• PMID: 37986659 (Publication Type: Journal Article)