Deletion of Exon 4 in the N-Acetylgalactosamine-4-Sulfatase Gene in a Taiwanese Patient with Mucopolysaccharidosis Type VI

Deletion of Exon 4 in the N-Acetylgalactosamine-4-Sulfatase Gene in a Taiwanese Patient with Mucopolysaccharidosis Type VI

WEI-DE LIN,^1,2 YU-YUAN KE,³ I-CHING CHOU,^4,5 CHUNG-HSING WANG^4,6 and FUU-JEN TSAI^4,7,8,9

¹Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
²School of Post Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan
³Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan
⁴Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan
⁵Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
⁶School of Medicine, China Medical University, Taichung, Taiwan
⁷Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan
⁸School of Chinese Medicine, China Medical University, Taichung, Taiwan
⁹Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan

Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), one of the enzymes required for the degradation of dermatan sulfate (DS). Accumulation of DS in connective tissue causes growth failure, resulting in short stature. Here, we observed a 5-year-old girl who was the only one affected member of her family and who presented with an exaggerated, convex curvature of the back at the age of one year. Abnormal excretion of DS in the urine and extremely low leukocyte ARSB activity were noted. The patient was suspected to have MPS VI. Direct DNA sequencing indicated that there was no mutation in the coding region of ARSB. However, RT-PCR analysis of RNA prepared from blood samples indicated the deletion of the entire exon 4. Further analysis of the genomic DNA by quantitative PCR confirmed a homozygous deletion of exon 4, an unusual intragenic deletion in ARSB. The deletion led to a truncated protein that lacks most of the catalytic domain. The patient received recombinant human ARSB as enzyme replacement therapy (ERT) at an early stage (2 years), and responded positively in terms of skeletal development and other developmental milestones. The early identification of type VI MPS patients and subsequent treatment with ERT may be beneficial for the clinical outcome of MPS VI patients. In addition, detailed gene analysis may enhance the ability to provide genetic counseling to families of patients affected by MPS VI.

keywords —— deletion mutation; dermatan sulfate accumulation; enzyme replacement therapy; mucopolysaccharidosis type VI; N-acetylgalactosamine-4-sulfatase

===============================

Tohoku J. Exp. Med., 2015, 235, 267-273

Correspondence: Chung-Hsing Wang, Department of Pediatrics, China Medical University Hospital, No. 2, Yude Road, 404, Taichung, Taiwan.

e-mail: d5894@mail.cmuh.org.tw