GM2 Gangliosidosis. Early infantile form. Tay-Sachs Disease. Hexosaminidase A deficiency.
Incidence
It is an autosomal recessive inherited disorder. The condition is especially frequently in Ashkenazic Jews. The incidence is 1/112,000 in general population but 1/3900 in Jewish population. Heterozygotes can be detected.
Clinical Characteristics
Tay-Sachs disease is an autosomal recessive inherited disorder associated with deficiency of hexosaminidase A. This results in intraneuronal accumulation of GM2 gangliosides. The disorder is seen primarily in Jewish children. The clinical characteristics are abnormal acousticomotor reaction, psychomotor deterioration, axial hypotonia, bilateral pyramidal signs and blindness with macular cherry red spots. No visceral or skeletal involvement. There is no abnormality by electron microscopy of bone marrow and leukocytes. No abnormal urinary excretion of oligosaccharides. The disease is always fatal, usually between the ages of three and five years. There is no known treatment. The children are born with normal height and weight and head circumference. The first sign of the disease is the startle response to sounds which occur after the second month of life. Cherry red spots may be seen between the fourth and always after the sixth month of life. Psychomotor regression is seen after the age of six months. The child loss the ability to maintain the sitting position and as the condition became worse, the infant becomes unable to roll over and loss all developmental milestones acquired before. After a few months, marked axial hypotonia with pyramidal signs and progressive limb spasticity is observed. Pendular nystagmus may be present from the fourth month. There is blindness after the patient's eight month. The cherry red spot is found in more than 90 % of cases. Electroretinogram is normal. After the first year of life, there is progressive macrocephaly. Seizures may occur late, tonic clonic type or minor motor seizures type, often elicited by noise. Abnormal EEG shows paroxysmal slow wave activity and multiple spike potentials and often hypsarrythmia as well. There is no peripheral nerve involvement. Nerve conduction velocity is normal. Spinal fluid is normal. No evidence of visceral nor skeletal involvement. No urinary excretion of oligosaccharides. The child is completely demented and decerebrated by the third year of life. The diagnosis requires isolated deficiency of hexosaminidase A with normal or elevated hexosaminidase B. The studies are usually done in leukocytes but also in cultured fibroblasts. Heterozygotes can be detected measuring hexosaminidase A in serum and leukocytes. There is no treatment available except supportive treatment.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
EB-W, EB-F. The diagnosis requires isolated deficiency of hexosaminidase A with normal or elevated hexosaminidase B. The studies are usually done in leukocytes but also in cultured fibroblasts.