Natural History and Molecular Characteristics of Korean Patients with Mucopolysaccharidosis Type III

Min-Sun Kim; Aram Yang; Eu-Seon Noh; Chiwoo Kim; Ga Young Bae; Han Hyuk Lim; Hyung-Doo Park; Sung Yoon Cho; Dong-Kyu Jin

doi:10.3390/jpm12050665

Natural History and Molecular Characteristics of Korean Patients with Mucopolysaccharidosis Type III

J Pers Med. 2022 Apr 21;12(5):665. doi: 10.3390/jpm12050665.

Authors

Min-Sun Kim¹, Aram Yang², Eu-Seon Noh¹, Chiwoo Kim³, Ga Young Bae¹, Han Hyuk Lim⁴, Hyung-Doo Park⁵, Sung Yoon Cho¹, Dong-Kyu Jin¹

Affiliations

¹ Department of Pediatrics, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
² Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea.
³ Department of Pediatrics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Korea.
⁴ Department of Pediatrics, Chungnam National University College of Medicine, Daejeon 35015, Korea.
⁵ Department of Laboratory Medicine and Genetics, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Abstract

Background: Mucopolysaccharidosis type III (MPS III) is an autosomal recessive lysosomal storage disorder characterised by progressive neurocognitive deterioration. MPS III subtypes are clinically indistinguishable, with a wide range of symptoms and variable severity. The natural history of this disorder within an Asian population has not yet been extensively studied. This study investigated the natural history of Korean patients with MPS III.

Methods: Thirty-four patients from 31 families diagnosed with MPS III from January 1997 to May 2020 in Samsung Medical Centre were enrolled. Clinical, molecular, and biochemical characteristics were retrospectively collected from the patients' medical records and via interviews.

Results: 18 patients had MPS IIIA, 14 had IIIB, and two had IIIC. Twenty (58.9%) patients were male. Mean age at symptom onset was 2.8 ± 0.8 years and at diagnosis was 6.3 ± 2.2 years. All patients with MPS IIIA and IIIB were classified into the rapidly progressing (RP) phenotype. The most common symptom at diagnosis was language retardation (88.2%), followed by motor retardation (76.5%), general retardation (64.7%), and hyperactivity (41.2%). Language retardation was more predominant in IIIA, and motor retardation was more predominant in IIIB. The mean age of the 13 deceased patients at the time of the study was 14.4 ± 4.1 years. The age at diagnosis and lag time were significantly older and longer in the non-survivor group compared with the survivor group (p = 0.029 and 0.045, respectively). Genetic analysis was performed in 24 patients with MPS III and identified seven novel variants and three hot spots.

Conclusion: This study is the first to analyse the genetic and clinical characteristics of MPS III patients in Korea. Better understanding of the natural history of MPS III might allow early diagnosis and timely management of the disease and evaluation of treatment outcomes in future clinical trials for MPS III.

Keywords: Sanfilippo syndrome; lysosomal storage disease; mucopolysaccharidosis III (MPS III); natural history.