P.1.1 Natural history of Ullrich congenital muscular dystrophy

Ullrich congenital muscular dystrophy (UCMD) is the second most common CMD in Japan. Mutations in either COL6A1 , COL6A2 , or COL6A3 gene, each encoding a subunit of collagen VI (COL6) are known to cause UCMD. To date, there is no cure for this disease and only limited information on the rate of disease progression. To characterize the natural history of UCMD, questionnaire-based nationwide survey was conducted from October 2010 to February 2011. We enrolled 33 patients (age at survey, 11.0 ± 6.6 years (mean ± SD)) with COL6 deficiency on immunohistochemistry in skeletal muscle: 5with complete and 28 with sarcolemma specific COL6 deficiency. Sequence analysis of COL6 genes was performed using genomic DNA from 32 patients, 19 (59.4%) of whom carried identifiable mutations. We analyzed the information on perinatal and developmental abnormalities, clinical manifestations, data of Cobb angle and % vital capacity (%VC). Age at muscle biopsy was 3.2 ± 2.0 years. Creatine kinase level was 315 ± 110 (IU/L) ( n = 31). Twenty-five (81%) of 31 patients walked independently by age 1.7 ± 0.5 years but lost this ability by age 8.8 ± 2.9 years ( n = 11). Six patients never walked independently. %VC was decreased exponentially with age, resulting in severe respiratory dysfunction before pubescence. Noninvasive ventilation was initiated at age 11.2 ± 3.6 years ( n = 13). Cobb angle over 30° was noted at age 9.9 ± 5.3 years ( n = 17). The maximum progression rate was 16.2 ± 10.0°/year ( n = 13). Scoliosis surgery was performed in 3 patients at respective ages 5, 9 and 10 years. Postoperative %VC was relatively well maintained in the youngest patient. The natural history of walking ability, respiratory function and scoliosis in UCMD patients was characterized. Although the age of onset varied, scoliosis, as well as restrictive respiratory dysfunction, progressed rapidly within years, once they appeared.