국내 뮤코지방증 환자의 임상적 특징 및 분자유전학적 분석에 대한 연구
Clinical features and molecular analysis of 12 Korean patients with Mucolipidosis II and III
Abstract
Mucolipidosis (ML) II alpha/beta and III alpha/beta are autosomal recessive inherited diseases caused by a dysfunction of the lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNac-1-phophotransferase). With dysfunction of this enzyme, digestive enzymes cannot be tagged with mannose-6-phosphate and transported to lysosomes. The substrates of digestive enzyme are accumulated in lysosome, which results in characteristic features of ML. Total 12 patients were diagnosed as ML II (n=5) or ML III (n=7) by lysosomal enzyme assay. Most patients showed developmental delay, multiple joint contracture and skeletal dysplasia, and cardiac involvement. All ML II patients showed hepatosplenomegaly. Most patients with ML III (n=6) showed valvular involvement only, while most patients with ML II showed hypertrophic cardiomyopathy (n=3) or left ventricular hypertrophy (n=1) in addition to valvular abnormalities. Two ML II patients needed respiratory support due to respiratory distress. We analyzed the GNPTAB gene, which encoded alpha and/or beta subunits of GlcNac-1-phophotransferase, in 4 ML II and 5 ML III patients from 8 families. We detected 11 pathogenic variants in GNPTAB, most of them were nonsense or deletion mutations. c.3565C>T (p.R1189X) accounted for 16.7% (3/16 allele). Due to bone pain associated with osteoporosis, two patients with ML III and one patient with ML II treated with intravenous pamidronate. The efficacy and safety of pamidronate treatment shouldbe investigated for longer time. This study demonstrates clinical features and molecular analysis in Korean patients with ML II and III.