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Clinical, biochemical and genetic profiles of patients with mucopolysaccharidosis type IVA (Morquio A syndrome) in Malaysia: the first national natural history cohort study

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dc.contributor.authorHuey Yin Leong
dc.contributor.authorNor Azimah Abdul Azize
dc.contributor.authorHui Bein Chew
dc.contributor.authorWee Teik Keng
dc.contributor.authorMeow Keong Thong
dc.contributor.authorMohd Khairul Nizam Mohd Khalid
dc.contributor.authorLiang Choo Hung
dc.contributor.authorNorzila Mohamed Zainudin
dc.contributor.authorAzura Ramlee
dc.contributor.authorMuzhirah Aisha Md Haniffa
dc.contributor.authorYusnita Yakob
dc.contributor.authorLock Hock Ngu
dc.date.accessioned2024-05-14T08:10:45Z
dc.date.available2024-05-14T08:10:45Z
dc.date.issued2019
dc.description.abstractBackground: Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage disease due to N-acetylgalactosamine-6-sulfatase (GALNS) deficiency. It results in accumulation of the glycosaminoglycans, keratan sulfate and chondroitin-6-sulfate, leading to skeletal and other systemic impairments. Data on MPS IVA in Asian populations are scarce. Methods: This is a multicentre descriptive case series of 21 patients comprising all MPS IVA patients in Malaysia. Mutational analysis was performed by PCR and Sanger sequencing of the GALNS gene in 17 patients. Results: The patients (15 females and 6 males) had a mean age (± SD) of 15.5 (± 8.1) years. Mean age at symptom onset was 2.6 (± 2.1) years and at confirmed diagnosis was 6.9 (± 4.5) years. The study cohort included patients from all the main ethnic groups in Malaysia – 57% Malay, 29% Chinese and 14% Indian. Common presenting symptoms included pectus carinatum (57%) and genu valgum (43%). Eight patients (38%) had undergone surgery, most commonly knee surgeries (29%) and cervical spine decompression (24%). Patients had limited endurance with lower mean walking distances with increasing age. GALNS gene analysis identified 18 distinct mutations comprising 13 missense, three nonsense, one small deletion and one splice site mutation. Of these, eight were novel mutations (Tyr133Ser, Glu158Valfs*12, Gly168*, Gly168Val, Trp184*, Leu271Pro, Glu320Lys, Leu508Pro). Mutations in exons 1, 5 and 9 accounted for 51% of the mutant alleles identified. Conclusions: All the MPS IVA patients in this study had clinical impairments. A better understanding of the natural history and the clinical and genetic spectrum of MPS IVA in this population may assist early diagnosis, improve management and permit timely genetic counselling and prenatal diagnosis.
dc.identifier.doihttps://doi.org/10.1186/s13023-019-1105-6
dc.identifier.urihttps://repository.nih.gov.my/handle/123456789/310
dc.identifier.urihttps://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1105-6
dc.language.isoen
dc.relation.ispartofOrphanet Journal of Rare Diseases
dc.relation.issn1750-1172
dc.relation.journalOrphanet Journal of Rare Diseases
dc.subjectDiagnosis
dc.subjectGALNS
dc.subjectMalaysia
dc.subjectMucopolysaccharidosis IVA
dc.subjectNatural history.
dc.titleClinical, biochemical and genetic profiles of patients with mucopolysaccharidosis type IVA (Morquio A syndrome) in Malaysia: the first national natural history cohort study
dc.typejournal-article
dspace.entity.typePublication
oaire.citation.endPage10
oaire.citation.issue1
oaire.citation.startPage1
oaire.citation.volume14
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