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.