Compound heterozygosity with a novel S222N GALT mutation leads to atypical galactosemia with loss of GALT activity in erythrocytes but little evidence of clinical disease

Benjamin Cocanougher; Umut Aypar; Amber McDonald; Linda Hasadsri; Michael J Bennett; W Edward Highsmith; Kristin D'Aco

doi:10.1016/j.ymgmr.2014.12.004

Compound heterozygosity with a novel S222N GALT mutation leads to atypical galactosemia with loss of GALT activity in erythrocytes but little evidence of clinical disease

Mol Genet Metab Rep. 2015 Jan 21:2:61-64. doi: 10.1016/j.ymgmr.2014.12.004. eCollection 2015 Mar.

Authors

Benjamin Cocanougher¹, Umut Aypar², Amber McDonald², Linda Hasadsri², Michael J Bennett^{3

4}, W Edward Highsmith², Kristin D'Aco¹

Affiliations

¹ University of Rochester School of Medicine and Dentistry, Department of Pediatrics, Division of Genetics, Rochester, NY, USA.
² Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
³ Metabolic Disease Laboratory, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
⁴ Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Abstract

Galactosemia is an inborn error of galactose metabolism caused by mutations in the GALT gene. Though early detection and galactose restriction prevent severe liver disease, affected individuals have persistently elevated biomarkers and often neuro-developmental symptoms. We present a teenage compound heterozygote for a known pathogenic mutation (H132Q) and a novel variant of unknown significance (S222N), with nearly absent erythrocyte GALT enzyme activity but normal biomarkers and only mild anxiety despite diet non-adherence. This case is similar to a previously reported S135L mutation. In this report we investigate the novel S222N variant and critically evaluate a clinically puzzling case.

Keywords: Diagnosis; Galactosemia; Pathogenesis.