Clinical, Biochemical and Molecular Profile of Variant Galactosemia in Children Detected by National Newborn Screening: A Pilot Study

Sylvia Capistrano-Estrada,1,2 Daffodil M. Canson1 and Catherine Lynn T. Silao1,2

1Institute of Human Genetics, National Institutes of Health,
University of the Philippines Manila;
2Department of Pediatrics, College of Medicine and
Philippine General Hospital, University of the Philippines Manila

Objective. The observed irregularities in the biochemical profile and the limited information on long-term outcomes among patients with Duarte variant (D/G) galactosemia have led to patient management variability. This study examined the molecular characteristics of Filipino patients with presumed variant galactosemia for confirmation of diagnosis. It also aimed to describe the corresponding biochemical, clinical and neurodevelopmental profiles in order to gain a better understanding of the patients with normal galactose metabolites in spite of low to absent GALT activity detected by the local newborn screening program.

Methods. Thirteen (13) patients who were presumed to have a variant form of galactosemia by national newborn screening between 2002 and 2010, and who previously underwent physical and neurodevelopmental assessment were included in the study. Repeat clinical, ophthalmologic and neurodevelopmental evaluations were done upon recruitment of participants. Direct sequence analysis of the coding region of the GALT gene was conducted to determine the patients’ genotypes.

Results. None of the patients’ genotypes were consistent with Duarte variant (D/G) galactosemia. Their genotypes reflect the normal total blood galactose levels in patients, but were inconsistent with the absent or trace GALT activity.

Conclusion. Molecular testing for the entire cohort of presumed “variant” galactosemia Filipino patients will provide better profiling of this condition. Re-evaluation and assessment of the current guidelines used by national newborn screening in classifying variant galactosemia are recommended.

Key Words: galactosemia, Duarte variant, GALT genotype, newborn screening