Mucolipidosis IV
Incidence
The condition is autosomal recessive. This condition has been observed in approximately 35 to 40 patients. It is a rare disease that affects mainly but not exclusively Ashkenazi Jews.
Clinical Characteristics
Failing vision and mental delay develop simultaneously following a normal neonatal period. Corneal opacity may be absent despite poor vision in the first months of life. The condition usually starts before age 6 to 12 months. Corneal clouding, retinal degeneration and profound motor and mental retardation are present but facial features are normal and there are no skeletal changes or visceromegaly. The rest of neurologic development and visual impairment used to become evident between three and eight months of age. Corneal opacity which is the most characteristic feature of mucolipidosis IV is generally observable in early infancy but may not be detected until the second year of life or later. Retinal degeneration with evident ambliopia are generally found and the ERG is extinct. Motor development is severely impaired. No patient has been able to walk without assistance. Hand play and other manual activity are grossly impaired. Mental development is very poor. Most children have no speech at all. There is no obvious psychomotor regression. Most children are short stature and with a small head circumference often below third percentile. There is no organomegaly, no bone changes and no facial dysmorphism. There is no mucopolysacchariduria or olygosacchariduria. The disease has a protactive curse which extends well into adolescence and early adulthood. Diagnosis is based on demonstration of lysosomal inclusions in conjunctiva and skin biopsies. The lysosomal deposits are seen on the electron microscopy as concentric membranous bodies similar to those seen in Tay-Sachs disease. Clear vacuoles are also observed. These deposits are also seen in leukocytes and liver, spleen and brain cells. There is accumulation of gangliosides in cultured fibroblasts. The enzyme defect is unknown. There is no treatment for the condition but the corneal clouding can be prevented and probably reversed by protecting the cornea with regular use of artificial tears or with contact lenses. Photophobia is noted in 25% of children. Some patients have striking hypotonia with extrapyramidal signs. There are no seizures. The urine has no MPS but contains large quantities of GM3 gangliosides, phospholipids and neutral glycolipids. Diagnosis is made by visualizing the polysaccharide lipid-containing inclusion organels using electron microscopy of conjunctiva or skin biopsy. The defect can be related to a partial defect of neuraminidase or sialidase but has not been confirmed. In summary, mucolipidosis IV is a rare disease that affects mainly but not exclusively Ashkenazi Jews. Again, the clinical features are visual disturbances, corneal opacities, retinal degeneration, motor delay and lack of mental progress. There may be self mutilation.
Precipitants
No
Provocation Tests
no
Diagnostic Procedures
Diagnosis is based on demonstration of lysosomal inclusions in conjunctiva and skin biopsies. The lysosomal deposits are seen on the electron microscopy as concentric membranous bodies similar to those seen in Tay-Sachs disease. Clear vacuoles are also observed. These deposits are also seen in leukocytes and liver, spleen and brain cells. There is accumulation of gangliosides in cultured fibroblasts. The enzyme defect is unknown. Diagnosis is made by visualizing the polysaccharide lipid-containing inclusion organels using electron microscopy of conjunctiva or skin biopsy. The defect can be related to a partial defect of neuraminidase or sialidase but has not been confirmed.