Early Diagnosis of Classic Homocystinuria in Kuwait through Newborn Screening: A 6-Year Experience.

Hind Alsharhan,Doaa I Sadik,May Al-Rushood,Yadav Girish,Buthaina Albash,Sumaya Alkanderi,Mohammad Al-Ali,Ahmad Alahmad,Parakkal Xavier Cyril,Yasser M E Elfeky ,Reem M Elshafie ,Rasha Alsafi ,Rehab M Abdelrahman ,Alaa A Elmonairy ,Amir A Ahmed ,Refat M Hassan ,Dina Ramadan ,Naser Ali ,Sara D Al-Enezi ,Usama M Elkazzaz ,Ayman M Salloum ,Lailá Bastaki

doi:10.3390/ijns7030056

Abstract

Kuwait is a small Arabian Gulf country with a high rate of consanguinity and where a national newborn screening program was expanded in October 2014 to include a wide range of endocrine and metabolic disorders. A retrospective study conducted between January 2015 and December 2020 revealed a total of 304,086 newborns have been screened in Kuwait. Six newborns were diagnosed with classic homocystinuria with an incidence of 1:50,000, which is not as high as in Qatar but higher than the global incidence. Molecular testing for five of them has revealed three previously reported pathogenic variants in the CBS gene, c.969G>A, p.(Trp323Ter); c.982G>A, p.(Asp328Asn); and the Qatari founder variant c.1006C>T, p.(Arg336Cys). This is the first study to review the screening of newborns in Kuwait for classic homocystinuria, starting with the detection of elevated blood methionine and providing a follow-up strategy for positive results, including plasma total homocysteine and amino acid analyses. Further, we have demonstrated an increase in the specificity of the current newborn screening test for classic homocystinuria by including the methionine to phenylalanine ratio along with the elevated methionine blood levels in first-tier testing. Here, we provide evidence that the newborn screening in Kuwait has led to the early detection of classic homocystinuria cases and enabled the affected individuals to lead active and productive lives.

Highlights

Kuwait is a small country situated in the northwestern part of the Arabian Gulf with a total area of 17,818 square kilometers [1]
The number of screened samples are typically higher than the number of screened newborns since the protocol of national newborn screening program (NBS) of Kuwait recommends collecting three dried blood spots (DBS) for premature babies over the first month of life
A total of six confirmed cases of HCU based on elevated plasma Met and total homocysteine (tHcy) have been identified since the year 2015 through the NBS program

Summary

Introduction

Kuwait is a small country situated in the northwestern part of the Arabian Gulf with a total area of 17,818 square kilometers [1]. In October 2014, the Kuwait Ministry of Health started a publicly funded expanded newborn screening program (NBS) meeting the highest international standards to screen for a wide range of metabolic and endocrine disorders, including a total of 22 disorders (Table 1) via testing dried blood spots (DBS) and replacing the old, limited NBS for congenital hypothyroidism and phenylketonuria that was introduced in 2005. The NBS program aims to screen all infants born in Kuwait; it initially only covered public hospitals until April 2015 when the private hospitals were included as they used to perform NBS testing individually. In May 2019, the NBS program, centered at the NBS Laboratory in the Kuwait Medical Genetics Center (KMGC), started covering 100% of the neonates born in Kuwait (Table 2; Figure 1)

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Results

Discussion

Conclusion