title: Galactose Epimerase Deficiency: Expanding the Phenotype.
abstract: Galactose epimerase deficiency is an inborn error of metabolism due to uridine diphosphate-galactose-4'-epimerase (GALE) deficiency. We report the clinical presentation, genetic and biochemical studies in two siblings with generalized GALE deficiency.Patient 1: The first child was born with a dysmorphic syndrome. Failure to thrive was noticed during the first year. Episodes of heart failure due to dilated cardiomyopathy, followed by liver failure, occurred between 12 and 42 months. The finding of a serum transferrin isoelectrofocusing (IEF) type 1 pattern led to the suspicion of a congenital disorder of glycosylation (CDG). Follow-up disclosed psychomotor disability, deafness, and nuclear cataracts.Patient 2: The sibling of patient 1 was born with short limbs and hip dysplasia. She is deceased in the neonatal period due to intraventricular hemorrhage in the context of liver failure. Investigation disclosed galactosuria and normal transferrin glycosylation.Next-generation sequence panel analysis for CDG syndrome revealed the previously reported c.280G>A (p.[V94M]) homozygous mutation in the GALE gene. Enzymatic studies in erythrocytes (patient 1) and fibroblasts (patients 1 and 2) revealed markedly reduced GALE activity confirming generalized GALE deficiency. This report describes the fourth family with generalized GALE deficiency, expanding the clinical spectrum of this disorder, since major cardiac involvement has not been reported before.
authors.affiliation: Unidade de Doenças Metabólicas, Centro de Desenvolvimento da Criança, Hospital Pediátrico - Centro Hospitalar e Universitário de Coimbra, EPE, Avenida Afonso Romão, Coimbra, 3000-206, Portugal. filipacdcosta@gmail.com.
authors.forename: Filipa
authors.initials: F
authors.lastname: Dias Costa
authors.affiliation: Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Sacha
authors.initials: S
authors.lastname: Ferdinandusse
authors.affiliation: Serviço de Cuidados Intensivos Pediátricos, Hospital Pediátrico - Centro Hospitalar e Universitário de Coimbra, EPE, Coimbra, Portugal.|Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Pinto
authors.affiliation: Serviço de Cuidados Intensivos Pediátricos, Hospital Pediátrico - Centro Hospitalar e Universitário de Coimbra, EPE, Coimbra, Portugal.|Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dias
authors.affiliation: Center for Human Genetics, University of Leuven, Leuven, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Keldermans
authors.affiliation: Unidade de Bioquímica Genética, Centro de Genética Médica Jacinto de Magalhães, Centro Hospitalar do Porto, Porto, Portugal.|Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP, Porto, Portugal.
authors.forename: Dulce
authors.initials: D
authors.lastname: Quelhas
authors.affiliation: Center for Human Genetics, University of Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
authors.affiliation: Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Petra A
authors.initials: PA
authors.lastname: Mooijer
authors.affiliation: Unidade de Doenças Metabólicas, Centro de Desenvolvimento da Criança, Hospital Pediátrico - Centro Hospitalar e Universitário de Coimbra, EPE, Avenida Afonso Romão, Coimbra, 3000-206, Portugal.|Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Diogo
authors.affiliation: Department of Pediatrics, Centre for Metabolic Disease, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.|Metabool Centrum - Universitair Ziekenhuis Leuven, Leuven, Belgium.
authors.forename: Jaak
authors.initials: J
authors.lastname: Jaeken
authors.affiliation: Unidade de Doenças Metabólicas, Centro de Desenvolvimento da Criança, Hospital Pediátrico - Centro Hospitalar e Universitário de Coimbra, EPE, Avenida Afonso Romão, Coimbra, 3000-206, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia
keywords: Congenital disorder(s) of glycosylation; GALE; Galactosemia; Generalized galactose epimerase deficiency