Clinical features
Family NMD02 (Figure 1A) had seven individuals while that of family ID01 had one child (Figure 1B) affected with Mucolipidosis II alpha/beta like syndrome (OMIM#252500) (Table 1). Five affected individuals in family NMD02 were siblings and alive when the study was initiated. Two (III:5, III:6) of these affected individuals died during the course of the study. The parents and six siblings of the five patients were healthy with no obvious phenotype. The affected siblings had similar phenotypes (Figure 1C-E). However, the phenotype of the youngest affected individual was less severe as compared to that manifested by the older siblings, supporting a progressive course of the disorder (Table 1). Coarsening of facial features was more severe in the oldest siblings. Two affected individuals (III:5 and III:6) lost walking ability as the disease progressed and became bed ridden in late teens. They both died in their early twenties. Cognition of all affected individuals was average and the patients responded to questions and their speech was not impaired. Complete blood counts of individuals III:9 and III:11 detected mild anemia but no other abnormality (Table 1). Clinical or imaging investigations apart from skeletal radiography were not possible due to limited access to proper health care.
Family ID01 was identified in Iran with one affected girl with the onset of symptoms at the age of 6 months (Figure 1F). She had severe skeletal dysplasia, coarse facial features, developmental delay, short stature, craniosynostosis, kyphoscoliosis, hip joint subluxation, abnormal teeth, upper airway problem and motor impairment. Brain MRI showed thinning of corpus callosum and mild ventriculomegaly. Heart echocardiography documented a small ventricular septal defect. Biochemical tests for metabolic disorders showed an increase in Iduronate-2 sulfatase (Table 1).
Radiographs of individuals III:9 and III:11 (Figure 2A-B) in family NMD02 indicated severe skeletal dysplasia reminiscent of dysostosis multiplex. The long bones were severely affected with prominent metaphyseal regions and abnormal epiphyses. Pelvic radiograph of individual III:11 revealed small iliac wings with abnormal proximal hips. The skeletal anomalies were more severe in the older sibling, supporting a progressive nature of the disorder.
Radiographs of the affected child from family ID01 indicated severe skeletal dysplasia reminiscent of dysostosis multiplex. Multiple hemivertebrae, paddle shape ribs, hypoplasia and flattening of acetabular roof were also revealed by radiography (Figure 2C). Diaphyseal widening in humerus with hypoplastic epiphysis and hypoplastic genoid fossa was evident. Moreover, hip radiographs indicated short iliac wings and left hip dislocation. The child died at the age of 5 years due to respiratory failure.