Natural history, clinical symptoms, and cognitive development of Japanese patients with mucopolysaccharidosis III.

Mucopolysaccharidosis type III (MPS III) is an autosomal recessive lysosomal storage disorder characterized by severe progressive neurocognitive deterioration. Currently, no definitive treatment for MPS III is available, although novel therapies are being developed. This retrospective study characterized the natural history, clinical symptoms, treatment strategies, and cognitive development of MPS III in Japan, which will provide the basis for evaluating the efficacy of new therapies. Twelve patients (three with MPS IIIA, nine with MPS IIIB) registered in the Japan Registration System for Metabolic & Inherited Diseases or their parents completed survey questions on patient background, diagnostic information, treatment history, and developmental age (DA). Mean age at diagnosis was 4 years and 7 months (standard deviation: 1 year and 6 months), with no notable difference between MPS IIIA and IIIB. All 12 patients had substantial developmental delay and progressive decline, as demonstrated by plotting DA against chronological age, as well as bone deformity, dysmorphic facial features (hirsutism), impaired motor and language development (language delay, hyperactivity, gait disorder), and sleep disturbance. Developmental delay had begun by approximately 3 years old when DA was usually first assessed, with regression occurring thereafter; regression was more gradual in MPS IIIB than in MPS IIIA. Most patients received daily care (e.g., tubal feeding) and medications to control symptoms (e.g., anticonvulsants). This was the first study to evaluate changes in DA, clinical symptoms, and treatment of patients with MPS III in Japan. These results can be used as natural history data in the future evaluation of new treatments.