An 8-month-old baby girl had normal growth and development for the first few months, but then progressively deteriorated with deafness, blindness, atrophied muscle, inability to swallow, and seizures. Early on in the diagnosis of the child, it was noticed that a cherry red macula was present in both eyes. Considering the child in the above case, measurement of which one of the following would enable one to determine whether the mutation were in the hex A or hex B gene?
The child is exhibiting the symptoms of either Tay-Sachs or Sandhoff disease, both of which are sphingolipidoses. The hexA gene codes for hexosaminidase A, whereas the hexB gene codes for hexosaminidase B. The hex A protein consists of one A and one B subunit and cleaves only GM2. The hex B protein is a B dimer and cleaves both GM2 and globoside. In Tay-Sachs disease, a loss of hex A activity, globoside degradation is normal because the hex B protein is normal. The loss of hex B activity affects both hex A (because one subunit is of the B variant) and hex B (dimer) activity, and globoside will accumulate in Sandhoff disease, but not in Tay-Sachs disease.
GM1
GM2
Globoside
Glucocerebroside
Lipids