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 | Full Text

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 | Full Text



Orphanet Journal of Rare Diseases

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

• Huey Yin LeongEmail authorView ORCID ID profile,
• Nor Azimah Abdul Azize,
• Hui Bein Chew,
• Wee Teik Keng,
• Meow Keong Thong,
• Mohd Khairul Nizam Mohd Khalid,
• Liang Choo Hung,
• Norzila Mohamed Zainudin,
• Azura Ramlee,
• Muzhirah Aisha Md Haniffa,
• Yusnita Yakob and
• Lock Hock Ngu

Orphanet Journal of Rare Diseases201914:143

https://doi.org/10.1186/s13023-019-1105-6

©  The Author(s). 2019

• Received: 16 March 2019
• Accepted: 26 May 2019
• Published: 14 June 2019

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.

Keywords

• Natural history
• Diagnosis
• Mucopolysaccharidosis IVA
• GALNS
• Malaysia