High prevalence of femoral head necrosis in Mucopolysaccharidosis type III (Sanfilippo disease): A national, observational, cross-sectional study

摘要

Background: Sanfilippo disease, or Mucopolysaccharidosis type III (MPS III), is a lysosomal storage disorder and a member of the mucopolysaccharidoses (MPSs). MPS III is clinically characterized by progressive neurodegeneration. Skeletal disease is not felt to be an important clinical component in MPS III patients, unlike in the other MPSs. We conducted radiographic studies in a relatively large group of MPS III patients and detected a high prevalence of osteonecrosis of the femoral head (ONFH). Methods: Thirty-three patients were included in the study. All the patients underwent an X-ray of the pelvis (anteroposterior view). All the X-rays were evaluated by a single, blinded radiologist using a modified Ficat classification system for ONFH (the stages ranged from 0 to IV, with increasing stages signifying more severe abnormalities). Clinical symptoms possibly related to hip disease were recorded. The patients were divided into different phenotypes based on mutational analysis and their plasma heparan sulfate (HS) levels. Results: In 21 of the 33 patients, the disease severity could be predicted by genotype. In 11 of the 12 remaining patients, the phenotype could be assessed via the plasma HS levels. Eight patients (24%) exhibited signs of ONFH (Ficat stage ≥ I), and 6 (75%) of them had bilateral changes. None of the patients with attenuated MPS III (n = 14) had ONFH. In 6 of the patients with a severe phenotype, hip dysplasia was detected as an additional finding. The 7 patients with Ficat stages ≥ II reported hip pain. Conclusions: Femoral head disease, which resembles ONFH, is common in patients with the severe MPS III phenotype. An evaluation of hip disease should be included in follow-up visits with MPS III patients.