{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:49:37Z","timestamp":1792763377879,"version":"4.5.0"},"reference-count":29,"publisher":"Walter de Gruyter GmbH","issue":"0","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Classical homocystinuria (HCU) is an autosomal recessive inborn error of metabolism, which is caused by the cystathionine-\u03b2-synthase (CBS: encoded by CBS<\/jats:italic>) deficiency. Symptoms of untreated classical HCU patients include intellectual disability (ID), ectopia lentis and long limbs, along with elevated plasma methionine, and homocysteine.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A total of 429 ID patients (age range: 1.6\u201323 years) were sampled from Northern areas of Punjab, Pakistan. Biochemical and genetic analyses were performed to find classical HCU disease in ID patients.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Biochemically, nine patients from seven unrelated families were identified with high levels of plasma methionine and homocysteine. Targeted exonic analysis of CBS<\/jats:italic> confirmed seven causative homozygous mutations; of which three were novel missense mutations (c.451G>T; p.Gly151Trp, c.975G>C; p.Lys325Asn and c.1039\u00a0+\u00a01G>T splicing), and four were recurrent variants (c.451\u00a0+\u00a01G>A; IVS4\u00a0+\u00a01 splicing, c.770C>T; p.Thr257Met, c.808_810del GAG; p.Glu270del and c.752T>C; p.Leu251Pro). Treatment of patients was initiated without further delay with pyridoxine, folic acid, cobalamin, and betaine as well as dietary protein restriction. The immediate impact was noticed in behavioral improvement, decreased irritability, improved black hair color, and socialization. Overall, health outcomes in this disorder depend on the age and symptomatology at the time of treatment initiation.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n With personalized treatment and care, such patients can reach their full potential of living as healthy a life as possible. This screening study is one of the pioneering initiatives in Pakistan which would help to minimize the burden of such treatable inborn errors of metabolism in the intellectually disabled patients.<\/jats:p>\n <\/jats:sec>","DOI":"10.1515\/jpem-2021-0508","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T19:30:37Z","timestamp":1639510237000},"source":"Crossref","is-referenced-by-count":5,"title":["Identification of three novel pathogenic mutations in cystathionine beta-synthase gene of Pakistani intellectually disabled patients"],"prefix":"10.1515","volume":"0","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0969-6609","authenticated-orcid":false,"given":"Muhammad","family":"Wasim","sequence":"first","affiliation":[{"name":"Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE) , Faisalabad , Pakistan"},{"name":"NIBGE-College, Pakistan Institute of Engineering and Applied Sciences (PIEAS) , Nilore , Islamabad , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haq N.","family":"Khan","sequence":"additional","affiliation":[{"name":"Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE) , Faisalabad , Pakistan"},{"name":"NIBGE-College, Pakistan Institute of Engineering and Applied Sciences (PIEAS) , Nilore , Islamabad , Pakistan"},{"name":"Department of Biological and Biomedical Sciences, Aga Khan University , Karachi , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hina","family":"Ayesha","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Allied & DHQ Hospitals, Faisalabad Medical University (FMU\/PMC) , Faisalabad , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazhar","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE) , Faisalabad , Pakistan"},{"name":"NIBGE-College, Pakistan Institute of Engineering and Applied Sciences (PIEAS) , Nilore , Islamabad , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Tawab","sequence":"additional","affiliation":[{"name":"Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE) , Faisalabad , Pakistan"},{"name":"NIBGE-College, Pakistan Institute of Engineering and Applied Sciences (PIEAS) , Nilore , Islamabad , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Irfan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Allied & DHQ Hospitals, Faisalabad Medical University (FMU\/PMC) , Faisalabad , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warsha","family":"Kanhai","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry , Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers , Duivendrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna M. I.","family":"Goorden","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry , Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers , Duivendrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lida","family":"Stroomer","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry , Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers , Duivendrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajja","family":"Salomons","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry , Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers , Duivendrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic M.","family":"Vaz","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry , Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers , Duivendrecht , The Netherlands"},{"name":"Departments of Pediatrics and Clinical Genetics , Amsterdam University Medical Centers, University of Amsterdam , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara D. M. van","family":"Karnebeek","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Clinical Genetics , Amsterdam University Medical Centers, University of Amsterdam , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8210-705X","authenticated-orcid":false,"given":"Fazli R.","family":"Awan","sequence":"additional","affiliation":[{"name":"Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE) , Faisalabad , Pakistan"},{"name":"NIBGE-College, Pakistan Institute of Engineering and Applied Sciences (PIEAS) , Nilore , Islamabad , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"2021121418372159297_j_jpem-2021-0508_ref_001","doi-asserted-by":"crossref","unstructured":"van Karnebeek, CDM. Evaluation of the child with developmental impairments. 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