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. 2024 Jan 10:38:101048.
doi: 10.1016/j.ymgmr.2024.101048. eCollection 2024 Mar.

Twelve-year review of galactosemia newborn screening in Taiwan: Evolving methods and insights

Hui-An Chen  1   2 , Rai-Hseng Hsu  1   2 , Li-Chu Chen  2 , Ni-Chung Lee  1   2 , Pao-Chin Chiu  3 , Wuh-Liang Hwu  2   4 , Yin-Hsiu Chien  1   2
Affiliations

Twelve-year review of galactosemia newborn screening in Taiwan: Evolving methods and insights

Hui-An Chen et al. Mol Genet Metab Rep. .

Abstract

Background: Galactosemia was introduced into Taiwan's routine newborn screening (NBS) program in 1985. This study presents a 12-year experience, emphasizing disease diagnosis and screening performance.

Method: NBS for galactosemia utilized dried blood spot samples taken 48-72 h post-delivery, with total galactose (TGal) level as the primary marker. Newborns with critical TGal levels were referred immediately, while those with borderline TGal underwent a recall test. GALT activity measurement was applied simultaneously as the second-tier marker. Further confirmatory tests, such as whole exome sequencing (WES), were conducted upon referral.

Results: From January 1st, 2011, to December 31st, 2022, 51 cases were identified from 817,906 newborns. Of these, nine individuals had persistently elevated TGal. Diagnoses included one case of GALT deficiency, one of GALM deficiency, and seven of GALE deficiencies. Notably, the classic galactosemia patient (GALT deficiency) presented with extreme high TGal and was referred to the hospital for diet management immediately. All affected patients were instructed to adopt a galactose-restricted diet. By the median age of 2.5 years, all exhibited normal development and liver function.

Conclusion: The incidence of classical galactosemia and its variants is extremely low in Taiwan. Incorporating WES into NBS has improved our ability to detect various galactosemia forms, enriching our understanding of the genetic underpinnings. While these newly discovered forms often present with milder initial elevations in TGal, specific biochemical investigations and regular monitoring are essential to understanding the long-term implications and outcomes.

Keywords: Epimerase deficiency galactosemia; GALE deficiency; Galactosemia; Newborn screening; Whole exome sequencing.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Diagnostic Flowchart for Galactosemia Screening and Management. Caption: The flowchart represents the decision-making process for the screening and subsequent management of galactosemia based on total galactose (TGal) levels measured by newborn screening (NBS) and galactose-1-phosphate uridyltransferase (GALT) enzyme activity assays. Extremely elevated TGal levels (over 99.99th percentile, approximately equal to 30 μmol/L) or abnormal GALT activity prompts immediate confirmatory testing, while TGal levels between 99.95th percentile (i.e. 18 when using the GSP® Neonatal Total Galactose assay) and 99.99th percentile (approximately 30 μmol/L) alone require further evaluation of GALT activity. Based on GALT activity and TGal levels, dietary restrictions may be implemented and adjustments made as additional test results become available.
Fig. 2
Fig. 2
Variations in Total Galactose Concentration Among Galactosemia Subtypes and Transient Hypergalactosemia. Caption: The scatter plot illustrates the total galactose concentration (y-axis) for patients across four distinct groups: GALT, GALE, GALM, and transient hypergalactosemia (Negative). Red squares represent the initial dried blood spot (DBS) galactose levels, the retest DBS by blue circles, and the confirmatory DBS by green triangles, where applicable.
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References

    1. Timson D.J. The molecular basis of galactosemia - past, present and future. Gene. Sep 10 2016;589(2):133–141. doi: 10.1016/j.gene.2015.06.077. - DOI - PubMed
    1. Wada Y., et al. Biallelic GALM pathogenic variants cause a novel type of galactosemia. Genet. Med. Jun 2019;21(6):1286–1294. doi: 10.1038/s41436-018-0340-x. - DOI - PubMed
    1. Cerone J., Rios A. Galactosemia. Pediatr. Rev. Oct 2019;40(Suppl. 1):24–27. doi: 10.1542/pir.2018-0150. - DOI - PubMed
    1. Welling L., et al. International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up. J. Inherit. Metab. Dis. Mar 2017;40(2):171–176. doi: 10.1007/s10545-016-9990-5. - DOI - PMC - PubMed
    1. Pasquali M., Yu C., Coffee B. Laboratory diagnosis of galactosemia: a technical standard and guideline of the American College of Medical Genetics and Genomics (ACMG) Genet. Med. Jan 2018;20(1):3–11. doi: 10.1038/gim.2017.172. - DOI - PubMed