Hexosaminidase heterodimeric isozyme A, along with cofactor GM2 Activator Protein, catalyzes the degradation of GM2 gangliosides, and is composed of subunits encoded by the HEXA and HEXB genes. Mutations involving HEXA are the main cause of Tay-Sachs disease. At my facility, we do not test in-house for this isozyme fraction, or for total hexosaminidase. The test is available as a send-out using whole blood or serum. Other hexosaminidase isozymes (B, S, and the cytosolic C and D) are not tested for routinely. Only hexosaminidase C, which is actually the bifunctional protein NCOAT encoded by MGEA5, posesses a known physiologic function, being linked to diabetes mellitus Type 2. By the way, mutations in both HEXA and HEXB result in deficiencies in both hexosaminidase A and B, clinically Sandhoff disease, a lipid storage otherwise disorder indistinguishable from Tay-Sachs disease. Make no mistake, though. Sandhoff is not the same entity as the Tay-Sachs AB variant. And while I am rambling on about Tay-Sachs variants, if the total hexosaminidase and hexosaminidase A tests are negative in the face of clinical Tay-Sachs disease, a second-order hexosaminidase A MUGS test is available as a send-out that identifies the presence of an alpha chain site defect responsible for the rare B1 variant of the disease. And that’s all I have to say about that.
Posted in Clinical Pathology Tagged: chemistry, rare disease
Comments
To add a comment to the original post, click here.
You must be signed in to post a comment.
Sign in nowI already knew this. I learned this in medical school in our second year. I’m pretty sure it was on the USMLE Step 1. But, I’m glad you learned that today.
Bottom line: never ever trust an on-call intern….Amen!
I can dig it.
Please don’t also forget to restick the patient just in case it is a mechanical issue with the stick.
Excellent point, Doctor.