GM1 Gangliosidosis type III. Late onset chronic form. Adult form. Lysosomal beta-galactosidase deficiency.
Incidence
This condition is autosomal recessive disorder caused by deficiency of lysosomal beta-galactosidase. This type of GM1 gangliosidosis has been observed frequently in Japanese.
Clinical Characteristics
The onset is usually in late childhood or adolescence but may occur as early as four years of age or as late as in the third or fourth decade. The slowly progressive neurological signs most frequently observed are dysarthria and extrapyramidal signs especially dystonia. Seizures are uncommon. Cerebellar ataxia and myoclonus are generally not seen. Retinal changes, macular cherry red spots and corneal opacity are also absent. No dysmorphism or organomegaly is observed. Intellectual impairment if present is only slight or moderate. Mild bone changes like flattening of the vertebrae bodies may be observed. Occasionally they may cause a spinal compression. The chronic form also called adult form usually starts in the teens with wide range of clinical manifestations such as gait and speech disturbances, caused by persistent muscle hypertonia, dystonic posture and movements, facial grimacing, parkinsonian manifestation, seizures, and near normal intellect to severe intellectual impairment. The course of the disease extends over several decades. The clinical diagnosis is very difficult. Diagnosis is made by measurement of beta-galactosidase. Urine contains excessive amount of keratan sulfate-like substance and galactose-containing products derived from glycoproteins. Diagnosis is made by demonstration of deficiency of acid beta-galactosidase in leukocytes and cultured fibroblasts. Pathologically and biochemically this condition is similar to those earlier forms of GM1 gangliosidosis. There are variable skeletal abnormalities that may be present such as cortical thinness of the long bones, dysplasia of the femoral head, hypoplasia in vertebrae bodies, flatness of the vertebrae bodies, osteosclerosis of the skull. Other abnormalities may include hyperintensity lesions in the putamen on T-2 weighted and proton density imaging, ventriculomegaly, brain atrophy and atrophy of the caudate nuclei on the MRI.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
EB-W, EB-F. Diagnosis is made by measurement of beta-galactosidase. Urine contains excessive amount of keratan sulfate-like substance and galactose-containing products derived from glycoproteins. Diagnosis is made by demonstration of deficiency of acid beta-galactosidase in leukocytes and cultured fibroblasts. Pathologically and biochemically this condition is similar to those earlier forms of GM1 gangliosidosis.