GM2 Gangliosidosis. Chronic type. Juvenile and adult type. Hexosaminidase A deficiency.
Incidence
More than 40 cases have been reported. AR disease. The majority of patients are Jewish in origin.
Clinical Characteristics
This condition occurs at any time between early childhood and adulthood. In one third of cases, onset is before age ten years and as early as three years. Many cases have not been recognized until middle and even late adulthood. The clinical expression of the chronic form is extremely variable. There are prominent signs of lower neuron and spinal cerebellar dysfunction. Progressive dystonia and psychiatric manifestation are also common. Onset is insidious and progression is slow. The initial development is generally normal but some children have been clumsy initially and have some difficulty at school. Slowly progressive speech difficulty with dysarthria and stuttering, voice with nasal quality and difficulty in walking and coordination of limb movements may show at the beginning of the condition. Cerebellar ataxia and pyramidal signs may be prominent. Some patients have been reported to have a clinical picture of atypical spinal cerebellar degeneration or atypical Friedreich disease. Dystonia, supranuclear ophthalmoplegia and oculo-motor apraxia has been recorded. Vision is not impaired. Optic fundi is normal. All patients have involvement of the lower motor neurons leading to proximal and later distal weakness and amyotrophy of limbs. Also there are fasciculations and signs of denervation atrophy in the EMG. No sensory loss. Sensory nerve conduction velocity is normal. Some patients mimic spinal muscular atrophy or amyotrophic lateral sclerosis (ALS). Psychiatric disturbances are present in approximately half of the patients. Bizarre irrational behavior, episodes of depression and psychosis with hallucinations can occur at various stages of the disease, occasionally as one of the first manifestations. Intellectual deterioration is frequent but not constant and may be a late sign. Cerebellar atrophy can be seen with MRI. CSF is normal. EEG abnormalities are variable and nonspecific. The course of the disease is protracted and may extend over several decades, sometimes until middle adulthood. Diagnosis is difficult in view of its extraordinary diversity. Enzymatic screening makes diagnosis. Skin and rectal biopsies may be helpful in detecting typical intralysosomal inclusions but may be normal. Most patients have the ordinary type of hexosaminidase A deficiency.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
EB-W, EB-F. Diagnosis is difficult in view of its extraordinary diversity. Enzymatic screening makes diagnosis. Skin and rectal biopsies may be helpful in detecting typical intralysosomal inclusions but may be normal. Most patients have the ordinary type of hexosaminidase A deficiency.