NeurometPlus

Incidence

This conditon is inherited autosomal recessive. Approximately seventy patients have been reported or probably much more cases than these for types I and II.

Clinical Characteristics

In alpha-mannosidosis mildler juvenile form or type II, the clinical picture may be at first quite uncharacteristic. During the first year of life, motor development is normal or somewhat retarded. Later, speech is delayed and remains imperfect. In the second or third years, mental retardation becomes evident but variable in degree. Motor performance is poor and movements are clumsy. Progression of neurological abnormality is hardly noticeable at least for many years. Often, the diagnosis of cerebral palsy or developmental mental retardation is done but there is deafness, ocular findings, subtle facial dysmorphism, skeletal abnormalities in X-rays, recurrent respiratory infection, hematological findings and possible hepatomegaly. Hearing loss is usual and apparently early. Superficial corneal opacity and spokelike posterior lens opacities are distinctive findings. Slight to moderate dysmorphic features comprise prominent forehead, large jaw, depressed nasal bridge, coarse features, and hyperplasia of the gums. Vertebral bodies are ovoid, flattened or with a beak-like deformity like that of mucopolysaccharidosis. Scoliosis may be present. Poor trabeculation of the long bones, a thick cranial calvarium and synostosis of longitudinal suture are important radiological findings. Destructive synovitis may occur in older patients. The susceptibility to multiple upper respiratory tract infections with abundant nasal discharge appears in infancy and may persist throughout the disease. The liver may be enlarged. Hernias are often present. 20 to 90 % of lymphocytes in peripheral blood contain translucent vacuoles and many polymorphonuclear leukocytes have coarse granulations. Foamy histiocytes have occasionally being found in bone marrow. The disease has a protracted course extending well into adulthood. Late in the disease, spastic paraplegia and also hydrocephalus may occur as in MPS or mucopolysaccharidosis. Diagnostic testing include excessive amount of mannose-containing oligosaccharides excreted in urine. Thin layer chromatography will easily disclose the particular pattern of oligosacchariduria which is characteristic of this disease. There is no mucopolysacchariduria. The deficient enzyme lysosomal acid alpha-mannosidase may be detected in leukocytes and cultured fibroblasts but not reliable in plasma. Heterozygote detection is possible. Pathological findings include marked and widespread distention of neurons which contain in the electron microscopy multiple clear membrane-bound vacuoles with fine reticular granular inclusions and other types of deposits. Similar lysosomal vacuoles are found in liver and other organs. Treatment: Residual activity of alpha-mannosidase can be stimulated by zinc ions but oral therapy with zinc sulfate has not been beneficial. Bone marrow transplantation may be tried with some somatic effects of the disease reversed but storage within the brain apparently unchanged.

Precipitants

no

Provocation Tests

no

Diagnostic Procedures

EB-W, EB-F. Diagnostic testing include excessive amount of mannose-containing oligosaccharides excreted in urine. Thin layer chromatography will easily disclose the particular pattern of oligosacchariduria which is characteristic of this disease. There is no mucopolysacchariduria. The deficient enzyme lysosomal acid alpha-mannosidase may be detected in leukocytes and cultured fibroblasts but not reliable in plasma. Heterozygote detection is possible. Pathological findings include marked and widespread distention of neurons which contain in the electron microscopy multiple clear membrane-bound vacuoles with fine reticular granular inclusions and other types of deposits. Similar lysosomal vacuoles are found in liver and other organs.