Galactose epimerase deficiency: lessons from the GalNet registry.

Carlo Dionisi-Vici, M Estela Rubio-Gozalbo, Gerard T Berry, Karolina M Stepien, Anastasia Skouma, Sabine Scholl-Bürgi, Dorothea Möslinger, Eva Morava, Stephanie Grünewald, Matthias Gautschi, David J Timson, M Luz Couce, Ana Chiesa, Analía Cabrera, Alberto B Burlina, Samantha Banford, Rodrigo R Arantes, Didem Demirbas, Britt Derks

Journal: Orphanet journal of rare diseases 2022;17(1):331

PMID: 36056436

Free Full Text on BioMed Central View on PubMed

Abstract

BACKGROUND

Galactose epimerase (GALE) deficiency is a rare hereditary disorder of galactose metabolism with only a few cases described in the literature. This study aims to present the data of patients with GALE deficiency from different countries included through the Galactosemia Network to further expand the existing knowledge and review the current diagnostic strategy, treatment and follow-up of this not well characterized entity.

METHODS

Observational study collecting medical data from December 2014 to April 2022 of 22 not previously reported patients from 14 centers in 9 countries. Patients were classified as generalized or non-generalized based on their genotype, enzyme activities in different tissues and/or clinical picture and professional judgment of the treating physician.

RESULTS

In total 6 patients were classified as generalized and 16 as non-generalized. In the generalized group, acute neonatal illness was reported in 3, cognitive and developmental delays were present in 5 and hearing problems were reported in 3. Four generalized patients were homozygous for the genetic variant NM_001008216.2:c.280G > A (p.Val94Met). In the non-generalized group, no clearly related symptoms were found. Ten novel genetic variants were reported in this study population.

CONCLUSION

The phenotypic spectrum of GALE deficiency ranges from asymptomatic to severe. The generalized patients have a phenotype that is in line with the 9 described cases in the literature and prescribing dietary interventions is the cornerstone for treatment. In the non-generalized group, treatment advice is more difficult. To be able to offer proper counseling, in addition to red blood cell enzyme activity, genetic studies, transferrin glycoform analysis and enzymatic measurements in fibroblasts are recommended. Due to lack of facilities, additional enzymatic testing is not common practice in many centers nor a tailored long-term follow-up is performed.

Address: Department of Pediatrics and Clinical Genetics, Maastricht University Medical Centre+, P. Debyelaan 25, P.O. Box 5800, 6229 HX, Maastricht, The Netherlands.; GROW, Maastricht University, Maastricht, The Netherlands.; MetabERN: European Reference Network for Hereditary Metabolic Disorders, Udine, Italy.; UMD: United for Metabolic Diseases Member, Amsterdam, The Netherlands.; Division of Genetics and Genomics, Harvard Medical School, Boston Children's Hospital, 3 Blackfan Circle, Center for Life Science Building, Suite 14070, Boston, MA, 02115, USA.; Special Service of Medical Genetics, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; South Eastern Health and Social Care Trust, Downpatrick, BT30 6RL, UK.; Division of Inherited Metabolic Diseases, University Hospital, Via Orus 2/B, 35128, Padua, Italy.; Nutrition Department, Hospital de Niños V.J. Vilela, Sante Fe, Rosario, Argentina.; Department of Endocrinology, Hospital de Niños Ricardo Gutièrrez, Buenos Aires, Argentina.; Metabolic Unit, IDIS, Department of Neonatology, University Clinical Hospital of Santiago de Compostela. Calle Choupana, s/n, 15706, Santiago de Compostela, Spain.; Division of Metabolism, Bambino Gesu Children's Research Hospital IRCCS, Piazza S Onofrio 4, 00165, Roma, Italy.; Division of Paediatric Endocrinology and Metabolism, Department of Paediatrics, University Hospital Bern, Inselspital, Freiburgstrasse 15, CH-3010, Bern, Switzerland.; Metabolic Medicine Department, NIHR Biomedical Research Center (BRC), Institute for Child Health, Great Ormond Street Hospital, University College London, London, UK.; Department of Clinical Genomics and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.; Clinic for Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.; Institute of Child Health, Aghia Sophia Children's Hospital, Thivon & Papadiamantopoulou, 11527, Athens, Greece.; Adult Inherited Metabolic Disorders Department, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, Greater Manchester, UK.; School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton, BN2 4GJ, UK.; Department of Pediatrics and Clinical Genetics, Maastricht University Medical Centre+, P. Debyelaan 25, P.O. Box 5800, 6229 HX, Maastricht, The Netherlands. [email protected].; GROW, Maastricht University, Maastricht, The Netherlands. [email protected].; MetabERN: European Reference Network for Hereditary Metabolic Disorders, Udine, Italy. [email protected].; UMD: United for Metabolic Diseases Member, Amsterdam, The Netherlands. [email protected].

DOI: 10.1186/s13023-022-02494-4

Link outs

Free resources

Full Text Sources:

Miscellaneous:

https://assays.cancer.gov/CPTAC-1595

MeSH Terms: Galactosemias, Genotype, Homozygote, Humans, Registries, UDPglucose 4-Epimerase