Lysosomes and Lysosomal Storage Diseases

When observed under a microscope, complex animal cells, such as human cells, reveal themselves to be composed of a variety of smaller structures called organelles. Organelles serve specific functions within cells, ranging from protein and energy production to storage. Lysosomes are the organelles tasked with waste management in the cell. Structurally speaking, lysosomes are essentially a membrane that contains a variety of enzymes referred to collectively as acid hydrolases. With a pH level around 5, the interior of a lysosome has approximately the same level of acidity as black coffee.

Lysosomal markers: GALNS antibody

Lysosomal Storage Diseases

According to the National Center for Biotechnology Information, the primary function of lysosomes is to break down a variety of waste materials in the cell, such as polysaccharides, DNA, RNA, and proteins. They can also serve a role in cell health by digesting viruses, microbes and other organelles. They are thought to play a role in autophagic, programmed cell death, in which the cell essentially digests itself a piece at a time. There is, however, some debate regarding the relationship between autophagy and programmed cell death.
For the most part, lysosomes perform their waste management duties wholly unnoticed in the human body. There are, however, over 50 known genetic diseases that affect lysosomes in one way or another. These diseases are collected beneath the umbrella term of lysosomal storage diseases. Broadly speaking lysosomal storage diseases occur when a person’s lysosomes lack or have a severe deficit of one of the enzymes normally found in them. This deficit inhibits the cells from breaking down a specific type of cellular waste, such as lipids or proteins, which accumulate in the person’s body.

The majority of lysosomal storage diseases are autosomal recessive in nature. For an autosomal recessive disease to develop both parents must carry a copy of a defective gene and a child must inherit the defective gene from both parents. There is a one in four chance of a child inheriting the defective gene from both parents. A very small subset of lysosomal storage diseases are X-linked, meaning that the genetic defect is carried in the X chromosome, but the development of the X-linked diseases can depend on the sex of child, such as Hunter’s Syndrome which predominantly affects males, or affect both males and females, such as Fabry’s Disease.

There is no uniform set of symptoms associated with lysosomal storage diseases. Some of the conditions present with developmental delays, while others can cause neurological problems, bone growth deformity, organ problems or sense impairments, such as blindness. The symptoms can also vary in severity from individual to individual and based on the time disease onset. Schindler disease, for example, tends to result in severe impairment of cognitive and motor abilities, while the adult onset version tends to result in comparatively mild cognitive impairment.

There is no uniform age of onset, though these diseases do occur much more common in children than adults. In some cases, variations of the disease can have different onset times. Tay – Sachs disease, for instance, has three distinct types: infantile, juvenile, and adult/late onset. All three versions are characterized by physical and cognitive decline and the disease is, at present, always fatal. The occurrence of lysosomal storage diseases are exceedingly rare, generally occurring at rate of about 1 case per every 100,000 or less for each disease, though the rate is higher when the diseases are considered as a group.

Due to the relatively small number of cases of each disease, the clinical research necessary to develop safe, effective treatment options has been slow. Additionally, not every treatment option is appropriate or effective across the board. One of the more prevalent treatments is called enzyme replacement therapy, in which the patient receives the enzyme missing from their lysosomes intravenously. Two of the three types of Gaucher’s Disease, the most common of the lysosomal storage diseases, respond to enzyme replacement therapy. Bone marrow transplants have shown positive results in treating some of the diseases or, in the case of Hunter’s Syndrome, mitigating some of their symptoms. Future therapies may include pharmaceuticals, of which a few are available or in clinical trials, and there is the possibility that gene therapies may offer a solution one day. In the meantime, treatments tend to focus on symptom reduction and, where necessary, pain management.

Reference

National Center for Biotechnology Information: Lysosomes