Galactose epimerase deficiency: lessons from the GalNet registry.
Galactose epimerase deficiency
Galactose-restricted diet
Galactosemia type III
Galactosemias Network
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
02 09 2022
02 09 2022
Historique:
received:
24
05
2022
accepted:
15
08
2022
entrez:
2
9
2022
pubmed:
3
9
2022
medline:
9
9
2022
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 36056436
doi: 10.1186/s13023-022-02494-4
pii: 10.1186/s13023-022-02494-4
pmc: PMC9438182
doi:
Substances chimiques
UDPglucose 4-Epimerase
EC 5.1.3.2
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
331Informations de copyright
© 2022. The Author(s).
Références
J Biol Chem. 2005 Apr 8;280(14):13493-502
pubmed: 15701638
Am J Hum Genet. 2006 Jan;78(1):89-102
pubmed: 16385452
J Inherit Metab Dis. 1998 Jun;21(4):341-50
pubmed: 9700591
J Inherit Metab Dis. 1988;11 Suppl 2:249-51
pubmed: 3141714
JIMD Rep. 2017;37:19-25
pubmed: 28247339
Proc Natl Acad Sci U S A. 1971 Nov;68(11):2660-3
pubmed: 4941982
Lancet. 1995 Oct 21;346(8982):1073-4
pubmed: 7564790
Glycobiology. 2005 Dec;15(12):1268-76
pubmed: 16037488
Arch Dis Child. 1981 Nov;56(11):885-7
pubmed: 7305435
Hum Mol Genet. 2019 Jan 1;28(1):133-142
pubmed: 30247636
Am Fam Physician. 2017 Jul 1;96(1):36-43
pubmed: 28671370
Pediatrics. 1994 Oct;94(4 Pt 1):558-65
pubmed: 7755691
Gene. 2013 Jul 25;524(2):95-104
pubmed: 23644136
Mol Genet Metab. 2005 Jan;84(1):32-8
pubmed: 15639193
JIMD Rep. 2012;2:113-7
pubmed: 23430863
Am J Med Genet A. 2021 Oct;185(10):3118-3121
pubmed: 34159722
Mol Syndromol. 2020 Dec;11(5-6):320-329
pubmed: 33510604
Helv Paediatr Acta. 1973 Dec;28(6):497-510
pubmed: 4785150
Orphanet J Rare Dis. 2019 Apr 27;14(1):86
pubmed: 31029175
J Pediatr. 1983 Dec;103(6):927-30
pubmed: 6549612
Glycobiology. 1998 Apr;8(4):351-7
pubmed: 9499382
Biochemistry. 2000 May 16;39(19):5691-701
pubmed: 10801319
J Inherit Metab Dis. 2017 Mar;40(2):169-170
pubmed: 27837294
Arch Dis Child. 1999 Apr;80(4):374-6
pubmed: 10086948
J Inherit Metab Dis. 1983;6(1):17-20
pubmed: 6408303
Am J Hum Genet. 1999 Feb;64(2):462-70
pubmed: 9973283
Indian J Pediatr. 2010 Aug;77(8):909-10
pubmed: 20725869
Gene. 2013 Sep 10;526(2):318-24
pubmed: 23732289
Helv Paediatr Acta. 1972 Jun;27(2):125-30
pubmed: 4644860
J Biol Chem. 2020 Jan 31;295(5):1225-1239
pubmed: 31819007
FEBS J. 2005 Dec;272(23):6170-7
pubmed: 16302980