Lysosomal Storage Disease

November 12, 2012

Lysosomal Storage Disease

Lysosomal storage disease is a severe disorder caused by deficiencies or defects in the lysosomal enzymes. There are many variations on the disease all with varying symptoms and prognosis’.

What is lysosomal disease?

Lysosomal enzymes are responsible for the breakdown of macromolecules. Individuals who inherit a disorder of the lysosomal enzymes such as in the form of a defect of deficiency can end up with an excess of un-degraded metabolites. There are a vast amount of different kinds of deficiencies that all fall under the heading of lysosomal storage disease. However they can be categorised into groups depending on the affected metabolite. These groups are mucopolysaccharidoses, sphingolipidoses and mucolipidoses. A lysosomal storage disease can affect many areas of the body and they occur most commonly in the tissues richest in the involved substrate. For example the brain, which is rich in gangliosides substrate is the part of the body most commonly affected by gangliosidoses.

Lysosomal Storage Disease – Gaucher’s Disease

Gaucher’s disease falls into the category of sphingolipidoses and is the result of a glucocerebrosidase deficiency. There are 3 different types of Gaucher’s disease. Type I is the most common and can affect anyone between the ages of 2 and late adulthood. Some of the symptoms associated with this lysosomal storage disease include bone disease, late puberty, failure to grow and pingueculae. Results of x-ray scanning will reveal flaring at the ends of the longer bones in the body. Type II is very severe, occurs in infants and results in death before the age of 2. The primary symptom is progressive neurologic deterioration. Type III is a combination of type I and type II. Onset of the disease will occur during childhood and the symptoms vary in time and severity. In most cases those who live past adolescence will survive for many more years. Diagnosis can be made through analysing the enzymes and there is treatment available only for type I and type III. Treatment sometimes includes enzyme replacement, splenectomy or stem cell transplant.

Lysosomal Storage Disease – Niemann-Pick Disease

This is also a sphingolipidoses disease and can be split into groups type A and B. In type A sufferers have a massive deficiency in sphingomyelinase activity resulting in very progressive neurodegeneration and death before the age of 3 years old. In type B activity of the enzyme is only between 5 – 10 % abnormal. Symptoms of this type vary but most patients survive into adulthood. Diagnosis can be made using prenatal screening and enzyme testing. Research is being done into the use of bone marrow and stem cell transplantation as a form of treatment.

Lysosomal Storage Disease – Tay-Sachs Disease and Sandhoff’s Disease

These diseases are both forms of sphingolipidoses and are caused by a deficiency of hexosaminidase. In both diseases the primary symptoms are neurological and result in an early death. In Tay-Sachs disease, developmental issues are normally evidential by the age of 6 months with the child suffering from cognitive and motor deterioration leading to seizures, disability, paralysis and finally death by the age of 5 years old. In Sandhoff’s disease, progressive cerebral degeneration will begin at around 6 months causing symptoms including blindness, cherry-red macular spot and hyperacusis.

Lysosomal Storage Disease – Krabbe’s Disease

This is also a sphingolipidosis with themost common symptoms including blindness, deafness, disability and paralysis. This will eventually result in death. In affects infants and can be diagnosed through the detection of enzyme deficiency. Prenatal and neo-natal testing is sometimes performed in certain areas.

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