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

Orphanet Journal of Rare Diseases

卷:14

Meow Keong Thong¹  Muzhirah Aisha Md Haniffa²  Huey Yin Leong²  Lock Hock Ngu²  Wee Teik Keng²  Hui Bein Chew²  Azura Ramlee³  Liang Choo Hung⁴  Norzila Mohamed Zainudin⁴  Nor Azimah Abdul Azize⁵  Yusnita Yakob⁵  Mohd Khairul Nizam Mohd Khalid⁵ 

[1] Department of Paediatrics, Faculty of Medicine, University Malaya;

[2] Genetics Department, Hospital Kuala Lumpur, Ministry of Health Malaysia;

[3] Ophthalmology Department, Hospital Selayang, Ministry of Health Malaysia;

[4] Paediatric Department, Hospital Kuala Lumpur, Ministry of Health Malaysia;

[5] Unit of Molecular Diagnostics & Protein, Institute for Medical Research, Ministry of Health Malaysia;

关键词: Natural history;    Diagnosis;    Mucopolysaccharidosis IVA;    GALNS;    Malaysia;   

DOI  :  10.1186/s13023-019-1105-6

来源: DOAJ

【 摘 要 】

Abstract Background 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.

【 授权许可】

Unknown