Lysosomal storage diseases

[maxschauss]

Lysosomal storage diseases form a category of genetic disorders resulting from defective enzymes that normally function to break down unneeded molecules in cells. These enzymes do their work in the lysosome, a small compartment in a cell analogous to a garbage disposal. When any one of the lysosomal enzymes is defective, the molecules that would have been broken down by that enzyme instead accumulate and cause that individual's lysosomes to swell enormously, resulting in motor and mental deterioration, often to the point of premature death. The age of onset, rate of progression, and severity of the clinical symptoms observed in patients with the same defective lysosomal enzyme are highly variable. For many years, this variability in patients with the same defective enzyme puzzled scientists. Only recently have researchers begun to answer the riddle, thanks to a genetic analysis of a particular lysosomal storage disorder known as Tay-Sachs disease.
As in most lysosomal storage diseases, patients suffering from Tay-Sachs disease show both mental and motor deterioration and variability in age of onset, progression, and severity. Physicians have categorized the patients into three groups based on onset of the disease: infantile, juvenile, and adult. The infantile group begins to show neurodegeneration as early as six months of age and children rarely live beyond 3 years old. The first symptoms of the disease appear in juvenile cases between 2 and 5 years of age, with death usually occurring around age 15. Those with the adult form generally live out a normal lifespan, suffering from milder symptoms than those with the infantile and juvenile forms.
In Tay-Sachs disease, scientists were aware that molecules accumulated mainly in the brains of patients, but they did not discover the specific identity of the defective lysosomal enzyme responsible for the malfunction, hexosaminidase, until the 1960s. In 1985, the DNA sequence for the normal enzyme was determined. Shortly thereafter, the DNA sequences of genes encoding hexosaminidase from many Tay-Sachs patients were studied. It soon became apparent that not one or two but many different types of mutations in the hexosaminidase gene could result in Tay-Sachs disease. These different mutations resulted in various levels of impaired enzymatic activity; those in the infantile category had little to no normal activity, while those in the adult category suffered only moderate impairment. Scientists quickly hypothesized that the variation in age of onset and severity of Tay-Sachs disease correlated with the amount of residual enzymatic activity allowed by the particular genetic mutation a patient had. Though more research is needed to demonstrate similarity with other lysosomal storage diseases, the work done on Tay-Sachs disease has already offered a promising glimpse into the underlying mechanisms of these disorders.


I really don't get how to approach such a reading passage. As a non-native I (normally) should have some more problems than a native speaker, but still I should be able to solve this! But the questions are way too detailled, even when I read the answer I don't get WHY this is actually the answer. All this stuff you are talking about (Find the big picture, don't waste time on details, read quickly, make a sketch, blabla) is not at all helpful to answer questions about some detailled stuff presented in the text.

So how can I read such a passage in 3 min and at the same time get the details to answer these lovely Inference- etc -questions?

[tim]

Hi Max, we'd love to be able to help you improve your RC process, but most of the general advice we could give would largely be a repeat of advice that is already found on our forum and blog. Can you give us a quick rundown of which of these resources you've read and why they were unhelpful? Then we can perhaps point you to other resources you have not yet read or provide you with some feedback specific to your situation. The more detail you can provide us, the more likely it is that we'll be able to help you.