Multiple sulfatase deficiency. Mucosulfatidosis. Austin disease. Depression of the activity of arylsulfatase A and six other sulfatases.
Incidence
This condition is an autosomal recessive hereditary disorder. More than 50 cases have been reported from many countries.
Clinical Characteristics
Clinical manifestations present with neurological symptoms similar to early infantile metachromatic leukodystrophy except that early psychomotor development tends to be more severely retarded. Also, there are features reminiscent of mucopolysaccharidoses like moderate facial and skeletal deformities, hepatomegaly, deafness and inclusions in leukocytes. Another important feature is ichthyosis. This condition is an autosomal recessive hereditary disorder characterized by neurovisceral storage of sulfatides, mucopolysaccharides and cholesteryl sulfates due to depression of the activity of arylsulfatase A and six other sulfatases. The urine contains excessive quantities of sulfatides as well as heparan sulfate and dermatan sulfate. In half the cases, the neurological development during the first year of life was normal or moderately delayed. Neurologic regression begins between twelve and eighteen months, manifested by difficulty in walking, weakness of muscles, unsteadiness of movements and frequent falling. In all the patients, the development is very retarded and the child never walked. When children walk, they loss the ability to walk later. The neurological examination showed characteristic combination of pyramidal signs and peripheral neuropathy similar to metachromatic leukodystrophy. Peripheral neuropathy is present but tendon reflexes occasionally are present. However, there is always marked slowing of the nerve conduction velocity, both motor and sensory velocity. Non paralytic strabismus is frequent. Optic fundi is normal in the early stage. Head circumference is normal or reduced. The spinal fluid protein is usually elevated. With time, mental capacity regress and speech basically is never obtained. Generalized and myoclonic seizures are frequent. Motor deterioration continues, developing some arm tremor. By the age of four years, the child is quadriplegic with pseudobulbar signs and has lost all evidence of meaningful mental activity. At this age, optic atrophy is apparent. Other ocular abnormalities may be seen like grayish discoloration of macula and sometimes cherry red spots and pigmentary degeneration of the retina. There are other clinical features suggestive of mucopolysaccharide storage disease like facial features usually abnormal, with narrow prominent forehead, depressed nasal bridge, thick eyebrows, long eyelashes. The hands are often stubby and thumbs are short. Sternum can be prominent or concave. There is hepatomegaly and occasionally splenomegaly. X-ray abnormalities of bones are slight but significant. At the dorsal lumbar junction, the vertebral bodies are rounded with slight anterior beaking. Metacarpal bones are broad and poorly trabeculated with tapered ends. Other alterations may be found in the pelvis and femoral epiphyses and ribs. Peripheral blood and bone marrow show metachromatic inclusions similar to Hurler disease seen in lymphocytes. Deafness is frequent as in MPS. Corneal opacities are not present. A characteristic and nearly constant finding is a diffuse alteration of the skin usually in the form of fine ichthyosis, sometimes reported as thick and dry skin which is present since birth. The course of the disease extends over several years. Age of death varies from three to twelve years. The main laboratory findings for diagnosis is an increase in urinary secretion of sulfatides, dermatan sulfate and heparan sulfate. Enzyme essay in cultured skin fibroblasts show deficiency of arylsulfatase A but also loss of activity of arylsulfatase B and arylsulfatase C and four other sulfatases that degrade MPS. Other important laboratory finding are slow nerve conduction velocity, presence of inclusions in peripheral blood and bone marrow leukocytes, elevated CSF protein and intralysosomal inclusions in Schwann cells typical of metachromatic leukodystrophy in the sural nerve biopsy. There are some variants reported. One with early onset at birth, dysmorphism and skeletal changes. The other variant is from Saudi Arabia with severe dysostosis multiplex, large head and corneal clouding and mild mental retardation without ichthyosis nor deafness. There is no effective treatment available. Bone marrow transplantation has not been done.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
EB-F. The main laboratory findings for diagnosis is an increase in urinary secretion of sulfatides, dermatan sulfate and heparan sulfate. Enzyme essay in cultured skin fibroblasts show deficiency of arylsulfatase A but also loss of activity of arylsulfatase B and arylsulfatase C and four other sulfatases that degrade MPS. Other important laboratory finding are slow nerve conduction velocity, presence of inclusions in peripheral blood and bone marrow leukocytes, elevated CSF protein and intralysosomal inclusions in Schwann cells typical of metachromatic leukodystrophy in the sural nerve biopsy.