Galactose epimerase deficiency: lessons from the GalNet registry
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 t...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-022-02494-4 |
| _version_ | 1811274885391974400 |
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| author | Britt Derks Didem Demirbas Rodrigo R. Arantes Samantha Banford Alberto B. Burlina Analía Cabrera Ana Chiesa M. Luz Couce Carlo Dionisi-Vici Matthias Gautschi Stephanie Grünewald Eva Morava Dorothea Möslinger Sabine Scholl-Bürgi Anastasia Skouma Karolina M. Stepien David J. Timson Gerard T. Berry M. Estela Rubio-Gozalbo |
| author_facet | Britt Derks Didem Demirbas Rodrigo R. Arantes Samantha Banford Alberto B. Burlina Analía Cabrera Ana Chiesa M. Luz Couce Carlo Dionisi-Vici Matthias Gautschi Stephanie Grünewald Eva Morava Dorothea Möslinger Sabine Scholl-Bürgi Anastasia Skouma Karolina M. Stepien David J. Timson Gerard T. Berry M. Estela Rubio-Gozalbo |
| author_sort | Britt Derks |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T23:28:11Z |
| format | Article |
| id | doaj.art-7b30d0500cf94f298bf161b0d11d2fb6 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-12T23:28:11Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-7b30d0500cf94f298bf161b0d11d2fb62022-12-22T03:12:21ZengBMCOrphanet Journal of Rare Diseases1750-11722022-09-0117111210.1186/s13023-022-02494-4Galactose epimerase deficiency: lessons from the GalNet registryBritt Derks0Didem Demirbas1Rodrigo R. Arantes2Samantha Banford3Alberto B. Burlina4Analía Cabrera5Ana Chiesa6M. Luz Couce7Carlo Dionisi-Vici8Matthias Gautschi9Stephanie Grünewald10Eva Morava11Dorothea Möslinger12Sabine Scholl-Bürgi13Anastasia Skouma14Karolina M. Stepien15David J. Timson16Gerard T. Berry17M. Estela Rubio-Gozalbo18Department of Pediatrics and Clinical Genetics, Maastricht University Medical Centre+Division of Genetics and Genomics, Harvard Medical School, Boston Children’s HospitalSpecial Service of Medical Genetics, Hospital das Clínicas da Universidade Federal de Minas GeraisSouth Eastern Health and Social Care TrustMetabERN: European Reference Network for Hereditary Metabolic DisordersNutrition Department, Hospital de Niños V.J. VilelaDepartment of Endocrinology, Hospital de Niños Ricardo GutièrrezMetabERN: European Reference Network for Hereditary Metabolic DisordersMetabERN: European Reference Network for Hereditary Metabolic DisordersDivision of Paediatric Endocrinology and Metabolism, Department of Paediatrics, University Hospital BernMetabolic Medicine Department, NIHR Biomedical Research Center (BRC), Institute for Child Health, Great Ormond Street Hospital, University College LondonDepartment of Clinical Genomics and Department of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Pediatrics and Adolescent Medicine, Medical University of ViennaMetabERN: European Reference Network for Hereditary Metabolic DisordersInstitute of Child Health, Aghia Sophia Children’s HospitalAdult Inherited Metabolic Disorders Department, Salford Royal NHS Foundation TrustSchool of Pharmacy and Biomolecular Sciences, University of BrightonDivision of Genetics and Genomics, Harvard Medical School, Boston Children’s HospitalDepartment of Pediatrics and Clinical Genetics, Maastricht University Medical Centre+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.https://doi.org/10.1186/s13023-022-02494-4Galactose epimerase deficiencyGalactosemia type IIIGalactosemias NetworkGalactose-restricted diet |
| spellingShingle | Britt Derks Didem Demirbas Rodrigo R. Arantes Samantha Banford Alberto B. Burlina Analía Cabrera Ana Chiesa M. Luz Couce Carlo Dionisi-Vici Matthias Gautschi Stephanie Grünewald Eva Morava Dorothea Möslinger Sabine Scholl-Bürgi Anastasia Skouma Karolina M. Stepien David J. Timson Gerard T. Berry M. Estela Rubio-Gozalbo Galactose epimerase deficiency: lessons from the GalNet registry Orphanet Journal of Rare Diseases Galactose epimerase deficiency Galactosemia type III Galactosemias Network Galactose-restricted diet |
| title | Galactose epimerase deficiency: lessons from the GalNet registry |
| title_full | Galactose epimerase deficiency: lessons from the GalNet registry |
| title_fullStr | Galactose epimerase deficiency: lessons from the GalNet registry |
| title_full_unstemmed | Galactose epimerase deficiency: lessons from the GalNet registry |
| title_short | Galactose epimerase deficiency: lessons from the GalNet registry |
| title_sort | galactose epimerase deficiency lessons from the galnet registry |
| topic | Galactose epimerase deficiency Galactosemia type III Galactosemias Network Galactose-restricted diet |
| url | https://doi.org/10.1186/s13023-022-02494-4 |
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