Clinical and genetic features of Classic Galactosemia in the south of Brazil

Abstract

Introduction

Classic Galactosemia (CG) is a rare metabolic disorder that leads to acute neonatal hepatic dysfunction, with striking improvement after diet treatment. However, long-term complications, such as intellectual deficits, often persist.

Aim

To describe the demographic, clinical, and genetic features of CG in a cohort of patients from South Brazil.

Methods

Data were retrieved through medical charts review of CG patients followed in Rio Grande do Sul, Brazil.

Results

Thirty-one patients were included (families = 29; ethnicity: white = 20, indigenous Kaingang = 9, black = 2; female = 14). Five patients were diagnosed through private NBS and began treatment at a median age of 17 days (15–30), while others presented symptoms at 5 days (1–19) starting treatment at 27 days (5–4680). Eight patients presented Cerebral Palsy, Microcephaly, and/or Epilepsy, and two had died. Notable clinical findings were the “double cap sign” in Brain MRI (n = 1), pseudohyperglycemia (n = 3), and elevated chitotriosidase activity (n = 3). GALT sequencing was performed in 25/31 patients, and the most frequent causal variant found was c.563 A > G (p.Gln188Arg). Two novel variants were detected: c.164G > T (p.Gly55Val), associated with clinical variant galactosemia; and a novel haplotype c.[90dup; 529 A > G] (p.[His31Alafs*9;Met177Val]) detected in Kaingang patients. The minimal prevalence of CG in this Indigenous population was estimated in at least 1:900 live births.

Conclusion

This data improves the characterization of CG in symptomatic diagnosed patients and identifies a high incidence of CG in the Kaingang people due to a founder effect.