Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing
- PDF / 790,422 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 72 Downloads / 195 Views
RESEARCH
Open Access
Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing Sunita Bijarnia-Mahay1* , Johannes Häberle2, Anil B. Jalan3, Ratna Dua Puri1, Sudha Kohli1, Ketki Kudalkar3, Véronique Rüfenacht2, Deepti Gupta1, Deepshikha Maurya1, Jyotsna Verma1, Yosuke Shigematsu4, Seiji Yamaguchi5, Renu Saxena1 and Ishwar C. Verma1
Abstract Background: 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. Results: 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. Conclusions: 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. Keywords: Urea cycle, UCD, OTC deficiency, Citrullinemia, Argininosuccinic aciduria, Mutation, Prenatal diagnosis, Hyperammonemia
* Correspondence: [email protected]; [email protected] 1 Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(
Data Loading...
