Lysosomal storage diseases are caused by the malfunction enzymes that degrade several substances inhuman cells. These enzymes are found in sac-like structures inside cells called lysosomes. Lysosomes function as recycling units of each cell, which contain hundreds of thousands of them. Lysosomes harbor specific enzymes that breakdown several substances, including proteins, sugars, and lipids into simple products that the cell then utilizes to re-build these substances (Fig.1). Lysosomes and other related structures called endosomes are also essential for the transport or “trafficking” of different substances inside each cell. Each of lysosomal enzymes has specific substances that they are capable of degrading. In case there is a deficiency in one of these enzymes, there is a buildup of the substances, which these enzymes normally cleave, resulting initially in dysfunctional lysosomes, but systematically causing an aberrant function of an entire cell. Further, such defects in cells are then reflected in the malfunction of organs, which consist of these cells, resulting in severe and progressive health problems.
Figure 1 – Different Types of Treatment for Lysosomal Storage Diseases.
In general, the supportive/symptomatic treatment deals with the secondary effects of lysosomal enzyme deficiency. The specific treatments address either the accumulated substance (surgical procedures and substrate reduction therapy, SRT, a defective lysosomal enzyme by gene therapy (replacing the altered gene that generates a defective enzyme) or by enzyme augmentation therapy. This therapy is based on providing the normal enzyme through enzyme replacement therapy (ERT) or hematopoietic stem cell that provides donor cells that produce the normal that is taken by the patient’s disease cells with enlarged and dysfunctional lysosomes. A novel type of treatment is focused on enhancing the activity of the deficient enzyme that can still have a small but still insufficient enzyme activity.
Almost 60 LSD have been described as known lysosomal storage diseases. Some common LSD include:
Fabry Disease
Results from the accumulation of globotriaosylceramide. It is known as X-linked genetic disease, affects both male and females, causing pain, gastrointestinal problems, progressive kidney, heart and pulmonary problems, chronic pain and is associated with characteristic dark red skin spots
Gaucher Disease
Progressive LSD causing enlargement of spleen and liver, as well as bone lesions. Some forms of Gaucher disease also affect the brain, leading to severe neurological conditions
Neuronal ceroid Lipofuscinosis (also known as Batten’s Disease)
This is a group of neurodegenerative disorders named for the way the brain cells of patients look under the microscope. They mostly present in the first years of life and are characterized by visual failure, seizures and progressive cognitive decline. There is now a treatment for one subtype.
Niemann-Pick C Disease
Results in progressive neurological condition along with lung disease, as well as enlargement of the spleen and liver
Pompe Disease
Frequently fatal condition, which is presented in infancy. It results from glycogen build up in the heart and other organs, initially also known as acid maltase deficiency. If it manifests in childhood and adulthood, Pompe can cause progressive weakness of shoulder, hips, and respiratory muscles
Metachromatic Leukodystrophy and Krabbe Disease
Devastating LSD that results in progressive and neurodegenerative conditions. Recently adults have been described with milder forms that present with neuropathies and psychiatric problems.
The LSDs are relatively rare genetic disorders affecting 1 in 2,000-3,000 live births. Some specific LSD can occur more often in certain ethnic groups including Ashkenazi Jew (Gaucher, Niemann-Pick A, mucolipidosis-IV, Tay-Sachs), French-Canadian (Tay-Sachs), Cajun (Tay-Sachs), infantile neuronal lipofuscinosis (Finland). Because these diseases follow several patterns of inheritance, a person’s risk of passing this condition on to his or her children depends on the disease and the individual’s family background.