Changing clinical manifestations of Gaucher disease in Taiwan.
Enzyme replacement therapy
Gaucher disease
Newborn screening
Phenotype
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:
15 09 2023
15 09 2023
Historique:
received:
28
06
2022
accepted:
28
08
2023
medline:
18
9
2023
pubmed:
16
9
2023
entrez:
15
9
2023
Statut:
epublish
Résumé
Gaucher disease (GD) is a lysosomal storage disorder characterized by deficient glucocerebrosidase activity that results from biallelic mutations in the GBA1 gene. Its phenotypic variability allows GD to be classified into 3 subtypes based on the presence and extent of neurological manifestations. Enzyme replacement therapy (ERT) has been available for all patients with GD in Taiwan since 1998. Newborn screening (NBS) for GD has been available since 2015. This study attempted to unveil the clinical features of patients diagnosed with GD during different eras in Taiwan. Data from the health records of two tertiary hospitals responsible for two-thirds of the patients with GD in Taiwan were used. The study population included all patients identified as having GD between 1998, and April 2022, in these two hospitals for review. A total of 42 individuals were included, six of whom were diagnosed by NBS. Our cohort presented a higher proportion of GD3 individuals, both by clinical suspicion and by NBS diagnosis, than that reported worldwide. The major subtypes that were recognized following NBS diagnosis were GD2 and GD3. The majority of GD patients carry at least one p.Leu483Pro variant. The 5-year survival rates were 0% for GD2 patients and 100% for patients with other subtypes. Patients diagnosed during the post-NBS era were free of symptoms on initial presentation, except for those with the GD2 subtype. For those diagnosed earlier, ERT was shown to be effective in terms of improved hemograms and prevented bone crises. However, the neurological symptoms in GD3 patients progressed despite ERT intervention. ERT is essential in reversing the hematological presentations and preventing the skeletal complications of GD. Timely diagnosis of GD with NBS allows for early intervention with ERT to prevent disease progression and complications. However, the need for effective intervention for neurological dysfunction remains unmet.
Sections du résumé
BACKGROUND
Gaucher disease (GD) is a lysosomal storage disorder characterized by deficient glucocerebrosidase activity that results from biallelic mutations in the GBA1 gene. Its phenotypic variability allows GD to be classified into 3 subtypes based on the presence and extent of neurological manifestations. Enzyme replacement therapy (ERT) has been available for all patients with GD in Taiwan since 1998. Newborn screening (NBS) for GD has been available since 2015. This study attempted to unveil the clinical features of patients diagnosed with GD during different eras in Taiwan.
MATERIALS AND METHODS
Data from the health records of two tertiary hospitals responsible for two-thirds of the patients with GD in Taiwan were used. The study population included all patients identified as having GD between 1998, and April 2022, in these two hospitals for review. A total of 42 individuals were included, six of whom were diagnosed by NBS.
RESULTS
Our cohort presented a higher proportion of GD3 individuals, both by clinical suspicion and by NBS diagnosis, than that reported worldwide. The major subtypes that were recognized following NBS diagnosis were GD2 and GD3. The majority of GD patients carry at least one p.Leu483Pro variant. The 5-year survival rates were 0% for GD2 patients and 100% for patients with other subtypes. Patients diagnosed during the post-NBS era were free of symptoms on initial presentation, except for those with the GD2 subtype. For those diagnosed earlier, ERT was shown to be effective in terms of improved hemograms and prevented bone crises. However, the neurological symptoms in GD3 patients progressed despite ERT intervention.
CONCLUSION
ERT is essential in reversing the hematological presentations and preventing the skeletal complications of GD. Timely diagnosis of GD with NBS allows for early intervention with ERT to prevent disease progression and complications. However, the need for effective intervention for neurological dysfunction remains unmet.
Identifiants
pubmed: 37715271
doi: 10.1186/s13023-023-02895-z
pii: 10.1186/s13023-023-02895-z
pmc: PMC10502973
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
293Informations de copyright
© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).
Références
Ann Clin Transl Neurol. 2016 Feb 02;3(3):200-15
pubmed: 27042680
Am J Hematol. 2018 Feb;93(2):205-212
pubmed: 29090476
Clin Adv Hematol Oncol. 2012 Jun;10(6 Suppl 8):1-16
pubmed: 22895100
J Inherit Metab Dis. 2020 Sep;43(5):1056-1059
pubmed: 32242941
Blood Cells Mol Dis. 2020 Mar;81:102402
pubmed: 31918384
Am J Hematol. 2015 Jul;90 Suppl 1:S12-8
pubmed: 26096741
J Inherit Metab Dis. 2014 Jul;37(4):587-98
pubmed: 24820227
Blood Cells Mol Dis. 2006 May-Jun;36(3):422-5
pubmed: 16546416
Mol Genet Metab. 2021 Feb;132(2):49-58
pubmed: 33483255
J Clin Exp Hepatol. 2014 Mar;4(1):37-50
pubmed: 25755533
Nat Rev Dis Primers. 2018 Oct 1;4(1):27
pubmed: 30275469
Arch Intern Med. 2000 Oct 9;160(18):2835-43
pubmed: 11025794
Neurology. 2019 Dec 10;93(24):e2272-e2283
pubmed: 31719137
Genet Med. 2019 Mar;21(3):631-640
pubmed: 30093709
Semin Hematol. 2004 Oct;41(4 Suppl 5):4-14
pubmed: 15468045
Mol Genet Metab Rep. 2022 Apr 19;31:100867
pubmed: 35782609
Neurology. 2020 Oct 13;95(15):e2119-e2130
pubmed: 32764102
Mol Genet Metab. 2015 Feb;114(2):110-122
pubmed: 25435509
Orphanet J Rare Dis. 2022 Jun 18;17(1):234
pubmed: 35717194
Int J Mol Sci. 2017 Feb 17;18(2):
pubmed: 28218669
Ann N Y Acad Sci. 2016 May;1371(1):15-29
pubmed: 27144735
Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):389-394
pubmed: 33275748
Blood Cells Mol Dis. 2014 Sep;53(3):105-9
pubmed: 24984925
Mol Genet Metab. 2016 Feb;117(2):172-8
pubmed: 26674302
Front Neurol. 2022 Jun 06;13:907317
pubmed: 35734474
Mol Genet Metab. 2019 Feb;126(2):157-161
pubmed: 30448006
Expert Rev Hematol. 2016 Jan;9(1):51-8
pubmed: 26565753
Mol Genet Metab. 2011 Dec;104(4):438-47
pubmed: 21889384
AJR Am J Roentgenol. 1998 Dec;171(6):1693-8
pubmed: 9843315
Acta Paediatr Taiwan. 2001 Jul-Aug;42(4):231-5
pubmed: 11550412
Ann Transl Med. 2019 Jul;7(13):281
pubmed: 31392193