What is a lysosomal storage disease (LSD)
Tay-Sachs is classified as a lysosomal storage disease (LSD). These group of diseases are extremely rare and there are around 50 which have been identified. Like all things in the medical world it can be challenging to understand what they actually are if you do not come from a scientific background. Therefore, we have put together an explanation which may be easier to follow that attempts to translate medical terms into language most of us can make sense of.
The medical overview of LSDs is:
“Lysosomal storage diseases are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomal storage diseases result when a specific organelle in the body’s cells – the lysosome – malfunctions.
Lysosomal storage disorders are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of lipids, glycoproteins (sugar containing proteins) or so-called mucopolysaccharides. Individually, LSDs occur with incidences of less than 1:100.000, however, as a group the incidence is about 1:5000 – 1:10.000. Most of these disorders are autosomal recessively inherited, however a few are X-linked recessively inherited.”
To understand the above it is important to remember that Tay-Sachs occurs when there is a lack or reduced level of the Hex-A enzyme to clear away the waste protein GM2 (which is a lipid). Our “What is Tay-Sachs?” page can give you a good overview of the disease if there are some things in the previous sentence that are confusing.
A simple explanation of what the actual function of lysosomes are is that they are the cell’s waste disposal system and can digest many compounds. In terms of the medical explanation of LSDs, it is then possible to see why Tay-Sachs is classed as one of these diseases as the lysosomal dysfunction is due to two factors – a Hex-A deficiency resulting in a GM2 ganglioside build up.
Although Tay-Sachs is very rare in itself, when grouped as an LSD their occurrence is not so rare which is why people should be made aware that they exist. As an autosomal recessively inherited disease it means that both parents pass on a defected gene to their child. Although each parent does not have Tay-Sachs they are a carrier. Everyone has two copies of every gene on autosomal chromosomes, one from mother and one from father. When one is defected the other, in the case of Tay-Sachs, can override any problems the affected gene can cause. However, an individual with Tay-Sachs has unfortunately inherited the bad gene from both parents which causes the disease – this is why it is an autosomal recessively inherited condition. There is a one in four chance of a child having Tay-Sachs when both parents are carriers.
The medical explanation continues:
“The lysosome is commonly referred to as the cell’s recycling center because it processes unwanted material into substances that the cell can utilize. Lysosomes break down this unwanted matter via enzymes, highly specialized proteins essential for survival. Lysosomal disorders are triggered when a particular enzyme exists in too small an amount or is missing altogether. When this happens, substances accumulate in the cell. In other words, when the lysosome doesn’t function normally, excess products destined for breakdown and recycling are stored in the cell.”
This basically explains that the lack of the Hex-A enzyme in a child affected by Tay-Sachs results in the build up of the GM2 protein as it is not naturally cleared away by the enzyme.
Tay-Sachs as a LSD
To understand why Tay-Sachs is known as a LSD it is important to understand how they are classified. LSDs are generally classified by the nature of the primary stored material involved or by the type of protein that is deficient and is causing buildup. Therefore, Tay-Sachs is classified as a build up of lysosomal enzymes and also as a gangliosidosis lipid storage disorder.
Tay-Sachs was actually the first of these conditions ever described in 1881 although Pompe disease was the first classified as an LSD in 1963.