Abstract
Mucolipidosis type II (MLII) is a rare lysosomal storage disorder caused by defective trafficking of lysosomal enzymes. Severe skeletal manifestations are a hallmark of the disease including hip dysplasia. This study aims to describe hip morphology and the natural course of hip pathologies in MLII by systematic evaluation of plain radiographs, ultrasounds and magnetic resonance imaging (MRI). An international two-centered study was performed by retrospective chart review. All MLII patients with at least one pelvic radiograph were included. A total of 16 patients were followed over a mean of 3.5 years (range 0.2–10.7 years). Typical age-dependent radiographic signs identified were femoral cloaking (7/16), rickets/hyperparathyroidism-like changes (6/16) and constrictions of the supra-acetabular part of the os ilium (16/16) and the femoral neck (7/16). The course of acetabular and migration indexes (AI, MI) significantly increased in female patients. However, in the overall group, there was no relevant progression of acetabular dysplasia with a mean AI of 23.0 (range 5°–41°) and 23.7° (range 5°–40°) at the first and last assessments, respectively. Better knowledge on hip morphology in MLII could lead to earlier diagnosis, improved clinical management and enables assessment of effects of upcoming therapies on the skeletal system.
Highlights
Mucolipidosis type II and III (MLII/MLIII) are rare lysosomal storage disorders caused by a deficiency of N-acetylglucosamine-(GlcNAc) 1-phosphotransferase
The present study proves distinct age-depended radiographic changes in MLII
Sex differences exist, the overall course of acetabular development does not result in rapid hip dysplasia progression or secondary high hip dislocations
Summary
Mucolipidosis type II and III (MLII/MLIII) are rare lysosomal storage disorders caused by a deficiency of N-acetylglucosamine-(GlcNAc) 1-phosphotransferase. This enzyme catalyzes the first step of tagging lysosomal enzymes with mannose 6-phosphate (M6P) recognition markers for their receptor-mediated transport to the lysosomes [1]. Mutations in the GNPTAB gene coding for the α/β-subunit of GlcNAc-1-phosphotransferase are causing MLII (MIM #252500) or ML III alpha/beta (MIM #252600), whereas ML III gamma (MIM #252505) is originating from a defective GlcNAc-1-phosphotransferase γ-subunit due to mutations in the GNPTG gene [3,4,5]. MLIII alpha/beta patients are presenting an attenuated phenotype of MLII [6]. Individuals with a phenotype between MLII and MLIII are referred to as ML intermediate [7,8,9]
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