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

Hind Alsharhan 1 2 3, Amir A Ahmed 4 5, Naser M Ali 5, Ahmad Alahmad 6, Buthaina Albash 3, Reem M Elshafie 3 5, Sumaya Alkanderi 3 5, Usama M Elkazzaz 7, Parakkal Xavier Cyril 8, Rehab M Abdelrahman 4, Alaa A Elmonairy 3, Samia M Ibrahim 9, Yasser M E Elfeky 10, Doaa I Sadik 3, Sara D Al-Enezi 6, Ayman M Salloum 11, Yadav Girish 12, Mohammad Al-Ali 5, Dina G Ramadan 13, Rasha Alsafi 14, May Al-Rushood 4, Laila Bastaki 3

Affiliations

17 August 2021

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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.

Keywords: classic homocystinuria; incidence; methionine; molecular testing; newborn screening; total homocysteine.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1 The process of the newborn screening for classic homocystinuria in Kuwait. DBS: dried blood spot; NBS: newborn screening; AA: plasma amino acids; tHcy: total homocysteine.

Figure 1 The process of the newborn screening for classic homocystinuria in Kuwait. DBS: dried blood spot; NBS: newborn screening; AA: plasma amino acids; tHcy: total homocysteine.

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