Question

Briefly review the lysosomal storage diseases and discuss the laboratory approach to achieving a diagnosis of a
lysosomal storage disease. Use Pompe disease as an example. (min 500words)

Answer 1

Briefly review the lysosomal storage diseases and discuss the laboratory approach to achieving a diagnosis of a
lysosomal storage disease. Use Pompe disease as an example

Lysosomal storage diseases are a group of metabolic disorders that have been inherited as a result of defects in the function of the lysosomes. These are referred to as enzyme sacs that are present inside the cells hicb would be digesting larger molecules and the fragments get passed on the cell’s other part in order to be recycled.

There are a number of critical enzymes required in this process. If there is a defect in any one enzyme, there would be accumulation of the larger molecule inside the cell as a result of which it would be killed. Here disorders generally occur as a result of deficiency in one of the enzymes that are required for glycoproteins or lipid metabolism or the mucopolysaccharides. These are very rare and would be occulesser than 1 in 100,000. These dispersal could also be referred to as autosomal recessive.

In this disease, as the sosome will not be functioning in a normal manner, the products that should not be broken down will also be broken down. This is generally found in children, and children affected by this disease die young. Although mutations might be different for different disorders the base is the same.

Pompey disease is a form of lysosomal disorders. This disease is also referred to as the lycogen storage disease type II. This is an autosomal recessive disorder of metabolism in which there would be damage of the nerve cells as well as muscles all over the body. Glycogen is accumulated in the lysosomes in the body as a result of the deficiency of the enzyme aloha glucosidase. As a result of this glycogen build up, there would be myopathy if a muscle weakness that is progressive in nature. This in turn would be affecting a number of tissues all over the body, in particular heart, liver, nervous system and skeletal muscles.

If this is in the infantile form, the effect starts in the initial months of life. Some of the features would be hypotonia, cardiomegaly, muscle weakness, respiratory distress, failure to thrive, or difficulties in feeding. In babies, there is a floppy appearance, asking with delayed motor abilities.

Initial investigations start with chest x Ray, electrocardiography and electrocardiograph. There would be enlarged heart, along with conduction defects, which are non specific. The laboratory investigations or biochemical investigations include serum creative kinase test, which would be 10 times more elevated than normal levels. There would be elevation in serum aldolase as well, but this elevation would be lesser. Also, there would be elevation in lactic dehydrogenase, alanine transaminase and aspartame transaminase enzymes. The acid alpha glucosidase activities are estimated, in the fibroblasts of the patient through a skin biopsy. Also, the laboratorian will be performing muscle biopsy or testing the white blood cells. Also, sample choice is dependent on the laboratory resources.