Biochemical Screening of Intellectually Disabled Patients: A Stepping Stone to Initiate a Newborn Screening Program in Pakistan

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Abstract

Inborn errors of metabolism (IEMs) are rare group of genetic disorders comprising of more than 1,000 different types. Around 200 of IEMs are potentially treatable through diet, pharmacological and other therapies, if diagnosed earlier in life. IEMs can be diagnosed early through newborn screening (NBS) programs, which are in place in most of the developed countries. However, establishing a NBS in a developing country is a challenging task due to scarcity of disease related data, large population size, poor economy, and burden of other common disorders. Since, not enough data is available for the prevalence of IEMs in Pakistan; therefore, in this study, we set out to find the prevalence of various treatable IEMs in a cohort of intellectually disabled patients suspected for IEMs, which will help us to initiate a NBS program for the most frequent IEMs in Pakistan. Therefore, a total of 429 intellectually disabled (IQ <70) patient samples were collected from Pakistan. A subset of 113 patient samples was selected based on the clinical information for the detailed biochemical screening. Advance analytical techniques like, Amino Acid Analyzer, GC-MS, UHPLC-MS, and MS/MS were used to screen for different treatable IEMs like aminoacidopathies, fatty acid β-oxidation disorders and mucopolysaccharidoses (MPS) etc. A total of 14 patients were diagnosed with an IEM i.e., 9 with homocystinuria, 2 with MPS, 2 with Guanidinoacetate methyltransferase (GAMT) deficiency and 1 with sitosterolemia. These IEMs are found frequent in the collected patient samples from Pakistan. Thus, present study can help to take an initiative step to start a NBS program in Pakistan, especially for the homocystinuria having highest incidence among aminoacidopathies in the studied patients, and which is amenable to treatment. This endeavor will pave the way for a healthier life of affected patients and will lessen the burden on their families and society.

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A proposed nosology of inborn errors of metabolism

Carlos R Ferreira, Clara D.M. van Karnebeek, Jerry Vockley … (2018)

Purpose We propose a nosology for inborn errors of metabolism that builds on their recent redefinition. Methods We established a strict definition of criteria in order to develop a self-consistent schema for inclusion of a disorder into the nosology. Results We identified 1,015 well-characterized inborn errors of metabolism described in the literature. In addition, there are 111 less well-characterized conditions that may be inborn errors but do not meet strict criteria for inclusion in the current nosology. Conclusion We provide a master list of all currently recognized inborn errors of metabolism grouped according to their pathophysiological basis, with the hope of setting a standard against which new errors should be defined, as well as to promote awareness and foster collaboration in the area. With the rapid advances in the field of genetics in recent years, it is likely that this nosology will need to be updated in the near future, a process that will benefit from broader input and collaboration of experts in the field in order to improve future versions of the proposed classification.

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A targeted metabolomics approach for clinical diagnosis of inborn errors of metabolism

Abeer K. Malkawi, Anas Abdel Rahman, Majed Dasouki … (2018)

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Expanded Newborn Screening for Inborn Errors of Metabolism and Genetic Characteristics in a Chinese Population

Kejian Guo, Xuan Zhou, Xigui Chen … (2018)

The incidence of inborn errors of metabolisms (IEMs) varies dramatically in different countries and regions. Expanded newborn screening for IEMs by tandem mass spectrometry (MS/MS) is an efficient approach for early diagnosis and presymptomatic treatment to prevent severe permanent sequelae and death. To determine the characteristics of IEMs and IEMs-associated mutations in newborns in Jining area, China, 48,297 healthy neonates were recruited for expanded newborn screening by MS/MS. The incidence of IEMs was 1/1178 in Jining, while methylmalonic acidemia, phenylketonuria, and primary carnitine deficiency ranked the top 3 of all detected IEMs. Thirty mutations in nine IEMs-associated genes were identified in 28 confirmed cases. As 19 cases with the mutations in phenylalanine hydroxylase (PAH), solute carrier family 22 member 5 (SLC22A5), and methylmalonic aciduria (cobalamin deficiency) cblC type with homocystinuria (MMACHC) genes, respectively, it suggested that mutations in the PAH, SLC22A5, and MMACHC genes are the predominant causes of IEMs, leading to the high incidence of phenylketonuria, primary carnitine deficiency, and methylmalonic acidemia, respectively. Our work indicated that the overall incidence of IEMs is high and the mutations in PAH, SLC22A5, and MMACHC genes are the leading causes of IEMs in Jining area. Therefore, it is critical to increase the coverage of expanded newborn screening by MS/MS and prenatal genetic consulting in Jining area.

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Contributors

Muhammad Wasim: URI : http://loop.frontiersin.org/people/658968/overview

Haq Nawaz Khan: URI : http://loop.frontiersin.org/people/692185/overview

Hina Ayesha: URI : http://loop.frontiersin.org/people/756430/overview

Clara D. M. van Karnebeek: URI : http://loop.frontiersin.org/people/58570/overview

Fazli Rabbi Awan: URI : http://loop.frontiersin.org/people/640569/overview

Journal

Journal ID (nlm-ta): Front Neurol

Journal ID (iso-abbrev): Front Neurol

Journal ID (publisher-id): Front. Neurol.

Title: Frontiers in Neurology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-2295

Publication date (Electronic): 17 July 2019

Publication date Collection: 2019

Volume: 10

Electronic Location Identifier: 762

Affiliations

[1] ¹Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE) , Faisalabad, Pakistan

[2] ²Pakistan Institute of Engineering and Applied Sciences , Islamabad, Pakistan

[3] ³Department of Pediatrics, DHQ and Allied Hospitals, Faisalabad Medical University (FMU/PMC) , Faisalabad, Pakistan

[4] ⁴Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam University Medical Centers, University of Amsterdam , Amsterdam, Netherlands

[5] ⁵Departments of Pediatrics and Clinical Genetics, Emma Children's Hospital, Amsterdam University Medical Centers, University of Amsterdam , Amsterdam, Netherlands

Author notes

Edited by: Austen J. Milnerwood, Montreal Neurological Institute and Hospital, McGill University, Canada

Reviewed by: Liena Elbaghir Omer Elsayed, University of Khartoum, Sudan; Luca Marsili, University of Cincinnati, United States

*Correspondence: Clara D. M. van Karnebeek c.d.vankarnebeek@ 123456amsterdamumc.nl

Fazli Rabbi Awan awan.fr@ 123456gmail.com

This article was submitted to Neurogenetics, a section of the journal Frontiers in Neurology

†These authors have contributed equally to this work

Article

DOI: 10.3389/fneur.2019.00762

PMC ID: 6650569

PubMed ID: 31379716

SO-VID: 91c17815-d469-4c7f-abe3-7595506ce8f1

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 22 February 2019

Date accepted : 01 July 2019

Page count

Figures: 0, Tables: 3, Equations: 0, References: 49, Pages: 7, Words: 5186

Funding

Funded by: International Center for Genetic Engineering and Biotechnology 10.13039/100007675

Funded by: Higher Education Commission, Pakistan 10.13039/501100004681

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Biochemical Screening of Intellectually Disabled Patients: A Stepping Stone to Initiate a Newborn Screening Program in Pakistan

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Most cited references 33

A proposed nosology of inborn errors of metabolism

A targeted metabolomics approach for clinical diagnosis of inborn errors of metabolism

Expanded Newborn Screening for Inborn Errors of Metabolism and Genetic Characteristics in a Chinese Population

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