Sandhoff Disease – Tay-Sachs’ other evil twin

Tay-Sachs, as mentioned before, is part of the Lysosomal Storage Diseases, most of these are progressive, fatal and devastating. There are over 70 Lysosomal Storage Diseases and so the word ‘RARE’ starts to wear thin when we couple them all together.

Since starting this website I have learnt a lot, I suppose this is part of our journey now, to have a certain expertise on LSDs – I have learnt that rarity only means anything when it doesn’t affect you, once it does, it’s no longer rare, it’s reality!

I have been contacted by several parents who are going through the same as we are, some that have already completed the journey that we dread so much. A lot of these parents have children affected by Sandhoff Disease. Below is the rundown of what Sandhoff Disease is, and it is easy to understand why I call it Tay-Sachs’ other evil twin.

Sandhoff Disease is named after Konrad Sandhoff, a German chemist, who first described the disease in 1968. Sandhoff, is a progressive neurological autosomal recessive genetic disorder that appears in three forms: Classic Infantile, Juvenile and Late Onset or Chronic Sandhoff.

The fatty material (GM2 Gangliosides) which accumulates in the child’s brain cells is the same in Sandhoff and Tay-Sachs diseases. However, the enzyme deficiency in Sandhoff Disease arises from mutations in a different gene on a different chromosome: the beta (ß subunit of the hexosaminidase A enzyme (Hex-A) gene on chromosome 5 rather than the alpha (a subunit of the Hex-A gene on chromosome 15 for Tay-Sachs. Since both the alpha and the beta subunits are needed for the Hex-A function, children with Sandhoff are also deficient in Hex-A activity. However the B subunit is also essential for the functioning of another kind of hexosaminidase called Hex-B. As a result, children with Sandhoff disease lack normal levels of both Hex-A and Hex-B while those with Tay-Sachs still have Hex-B activity.

As with Tay-Sachs disease the severity of Sandhoff disease depends on the amount of residual enzyme that is produced. Children with virtually no hexosaminidase activity will have the infantile (acute onset) form of the disease. Those born with a small amount of hexosaminidase activity will have the juvenile, subacute form and those with still more activity will have a later onset adult (chronic) form of Sandhoff disease. The infantile form is the most severe and, unfortunately, the most common. The juvenile and adult forms of Sandhoff disease occur later and tend to be much more variable in their clinical features. The amount of residual enzyme, and therefore the clinical course, is determined by the specific mutation(s) in the ß-subunit of Hex-A.

Sandhoff disease, like Tay-Sachs, is an autosomal recessive disorder but, unlike Tay-Sachs, occurs more commonly in the non-Jewish population. In fact, given the higher incidence of Sandhoff in non-Jews and the clinical similarity of the two diseases, it is probable that some of the non-Jewish children diagnosed before the availability of the laboratory tests actually had Sandhoff disease.

Symptoms and progression of the disease occurs just as with Tay-Sachs and a cure would benefit all of those affected by both diseases.

 

 

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