Genotypic‐phenotypic features and enzyme replacement therapy outcome in patients with mucopolysaccharidosis VI from Turkey

• Published in: American journal of medical genetics. Part A 2017-11, Vol.173 (11), p.2954-2967
• Main Authors: Kılıç, Mustafa, Dursun, Ali, Coşkun, Turgay, Tokatlı, Ayşegül, Özgül, Rıza K., Yücel‐Yılmaz, Didem, Karaca, Mehmet, Doğru, Deniz, Alehan, Dursun, Kadayıfçılar, Sibel, Genç, Aydan, Turan‐Dizdar, Handan, Gönüldaş, Burhanettin, Savcı, Sema, Sağlam, Melda, Aksoy, Cemalettin, Arslan, Umut, Sivri, Hatice‐Serap
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Child; Child, Preschool; Chondroitin sulfate; Enzyme Replacement Therapy; Enzymes; Female; Gene Frequency; Genetic Association Studies; Genetic disorders; genotype; Heart; Heart diseases; Humans; Infant; Infant, Newborn; Liver; Lysosomal Storage Diseases - enzymology; Lysosomal Storage Diseases - genetics; Lysosomal Storage Diseases - pathology; Lysosomal Storage Diseases - therapy; Male; Maroteaux-Lamy syndrome; Metabolic disorders; Mucopolysaccharidosis; mucopolysaccharidosis type VI; Mucopolysaccharidosis VI - enzymology; Mucopolysaccharidosis VI - genetics; Mucopolysaccharidosis VI - pathology; Mucopolysaccharidosis VI - therapy; Mutation; N-Acetylgalactosamine-4-Sulfatase - genetics; outcome; Quality of Life; Sensory integration; Spleen; Sulfates; Turkey - epidemiology; Young Adult
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.38459

Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD) characterized by a chronic, progressive course with multiorgan involvement. In our study, clinical, biochemical, molecular findings, and response to enzyme replacement therapy (ERT) for at least 6 months were evaluated in 20 patients with MPS VI. Treatment effects on clinical findings such as liver and spleen sizes, cardiac and respiratory parameters, visual and auditory changes, joints’ range of motions, endurance tests and changes in urinary glycosaminoglycan excretions, before and after ERT were analyzed. ERT caused increased physical endurance and decreased urinary dermatan sulfate/chondroitin sulfate ratios. Changes in growth parameters, cardiac, respiratory, visual, auditory findings, and joint mobility were not significant. All patients and parents reported out an increased quality of life, which were not correlated with clinical results. The most prevalent mutation was p.L321P, accounting for 58.8% of the mutant alleles and two novel mutations (p.G79E and p.E390 K) were found. ERT was a safe but expensive treatment for MPS VI, with mild benefits in severely affected patients. Early treatment with ERT is mandatory before many organs and systems are involved.