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.
It can be inferred from the passage that which of the following statements is true of lysosomal storage diseases?
They are generally caused by mutations to the hexosaminidase gene.
They are undetectable until physical symptoms are present.
They can be fatal even when allowing some enzymatic activity.
They are most lethal when onset is in a patient's infancy.
Their causes were unknown before the 1950s.
ORA C
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.
It can be inferred from the passage that which of the following statements is true of lysosomal storage diseases?
They are generally caused by mutations to the hexosaminidase gene.
They are undetectable until physical symptoms are present.
They can be fatal even when allowing some enzymatic activity.
They are most lethal when onset is in a patient's infancy.
Their causes were unknown before the 1950s.
ORA C
