NeurometPlus

Incidence

This is an autosomal recessive disorder due to a deficiency of lysosomal acid beta-galactosidase which results in abnormal accumulation of GM1 gangliosides in the nervous system and of galactose-containing products.

Clinical Characteristics

This is an autosomal recessive disorder due to a deficiency of lysosomal acid beta-galactosidase which results in abnormal accumulation of GM1 gangliosides in the nervous system and of galactose-containing products that are derived from glycoproteins and keratan-like substances in visceral organs. The main clinical characteristics are symptoms that begin in the second year of life and survival up to twenty years. Neurological symptoms are mental retardation, spasticity, ataxia, rigidity, seizures, and progressive dementia. The fundi is normal. This condition begins in the second year of life, usually between twelve and eighteen months. The first definite sign is difficulty in walking and frequent falling. If the child has not begun to walk, increasing unsteadiness in sitting and attempting to stand is observed. Purposeful movements of the arms soon become ackward. Speech is lost rapidly. By the time the child reaches 2 or 3 years, standing and sitting without support is no longer possible and mental retardation is severe. Spastic quadriparesis is developed associated with prominent pseudobulbar signs that are responsible for drooling and dysphagia. Sometimes, seizures are frequent and may become a major problem late in the condition. Vision is normal. Non paralytic strabismus frequently occur. No abnormalities on the cornea nor retina is seen. Peripheral nerves are normal. Spinal fluid is normal. EEG is non specific abnormal, the latter the worse. There is no significant facial dysmorphism or clinically detectable skeletal deformities. Head size is normal. Liver and spleen are normal. Routine laboratory procedures may help in diagnosis. X-ray of the spine shows some moderate but constant changes such as mild anterosuperior hypoplasia of the vertebral bodies at the thoracolumbar junction. Mild hypoplasia of the acetabulae and proximal deformation of metacarpal bones are found. Some times, the skeletal is normal or mildly dysplastic. Bone marrow show few histiocytes with clear vacuoles or with fibrillary wrinkled cytoplasm resembling Gaucher\\\'s cells. Occasionally vacuolated lymphocytes are seen. At the end of the disease, the patient lapses in to a state of decorticate rigidity. Death terminates the illness between three to twenty years of age from pneumonia. Laboratory testing show urine contains a high amount of keratan-like substance and various galactose-containing substances derived from glycoproteins. Skin or conjunctival biopsies may reveal clear intracellular vacuoles similar to mucopolysacharidosis. The final diagnosis is based on enzymatic measurements and recently by exome sequencing identifying GLB1 gene mutations (c.602G>A, p.R201H). Also MALDI-TOF/TOF mass spectrometry analysis showing multiple oligosaccharides with terminal galactose residues. Deficiency of lysosomal acid beta-galactosidase is demostrated in leukocytes or cultured fibroblasts. The pathology of this condition is similar to the early infantile form. The average time from onset of symptoms to diagnosis is often greater than 5 years.

Precipitants

no

Provocation Tests

no

Diagnostic Procedures

EB-W, EB-F. Laboratory testing show urine contains a high amount of keratan-like substance and various galactose-containing substances derived from glycoproteins. Skin or conjunctival biopsies may reveal clear intracellular vacuoles similar to mucopolysacharidosis. The final diagnosis is based on enzymatic measurements and recently by exome sequencing identifying GLB1 gene mutations (c.602G>A, p.R201H). Also MALDI-TOF/TOF mass spectrometry analysis showing multiple oligosaccharides with terminal galactose residues. Deficiency of lysosomal acid beta-galactosidase is demostrated in leukocytes or cultured fibroblasts.