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.

Background: Leptospirosis is an emerging infectious disease of global significance, and is endemic in tropical countries, including Malaysia. Over the last decade, a dramatic increase of human cases was reported; however, information on the primary vector, the rat, and the Leptospira serovars circulating among the rat population is limited. Therefore, the present study was undertaken to isolate Leptospira and characterise the serovars circulating in the urban rat populations from selected main cities in Peninsular Malaysia. Methods: Rat trappings were carried out between October 2011 to February 2014 in five urban cities which were chosen as study sites to represent different geographical locations in Peninsular Malaysia. Microscopic agglutination test (MAT) and PCR were carried out to identify the Leptospiral serogroup and determine the pathogenic status of the isolates, respectively while pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD)-PCR were used to characterize the isolates. Results: Three rat species were identified from the three hundred and fifty seven rats captured with Rattus rattus, being the dominant rat species (285, 80 %) followed by Rattus norgevicus (53, 15 %) and Rattus exulans (19, 5 %). Only 39 samples (11.0 %) were positive by culture and further confirmed as pathogenic Leptospira by PCR. Significant associations were shown between host infection with locality, season, host-age and species. Based on MAT, two serogroups were identified in the population namely; L. borgpetersenii serogroup Javanica (n = 16) and L. interrogans serogroup Bataviae (n = 23). Pulsed-field gel electrophoresis (PFGE) distinguished the two serovars in the urban rat populations: L. borgpetersenii serovar Javanica (41 %), and L. interrogans serovar Bataviae (59 %). RAPD-PCR yielded 14 distinct patterns and was found to be more discriminative than PFGE. Conclusions: This study confirms two Leptospira serovars circulating among the urban rats population in Peninsular Malaysia namely; L. borgpetersenii serovar Javanica and L. interrogans serovars Bataviae. Despite the low number of isolates obtained from the rat population, this study suggests that rodent control programs and disease surveillance may help to reduce the possible risk of disease transmission.