Lysosomal storage diseases - rare but fatal

Lysosomal storage diseases (LSDs) are rare genetic conditions wherein there is abnormal accumulation of certain molecules and their metabolites in the lysosomes. A lysosome is a part of the smallest unit of our system: ‘the cell’. Lysosomes consist of enzymes responsible for the metabolism of various macromolecules such as complex carbohydrates, proteins, nucleic acids, lipids and fats. Accumulation of these molecules interferes with the normal functioning of the cell and leads to the clinical manifestations of lysosomal storage diseases.

Almost one in 100 individuals is estimated to carry the faulty genes that lead to lysosomal storage diseases. There are as many as 50 documented lysosomal diseases so far. Although considered to be a rare condition and statistical data estimates about one in 7,700 births is affected, hence making these diseases relatively common and significantly life threatening.

All lysosomal storage diseases are progressive, but the rate of progression severity of symptoms and organ systems affected varies between disorders and also within each disorder type. Lysosomal storage disease may affect various different organs or organ system of the body including the skeletal system, eyes, heart, lungs, kidneys, skin and most often the central nervous system. Although the underlying cause of these diseases is thought to be due to the effect of the accumulation of various macromolecules in the lysosomes on the cells, the precise mechanism causing this accumulation is not completely known. The pattern in which neurons degenerate in the various subtypes of lysosomal storage diseases is cell specific. Batten disease, Fabry disease, Hunter syndrome, Sanfillippo disease, Gaucher disease, Pompe’s disease, etc.

Batten disease
Batten disease is a fatal inherited disorder of the central nervous system that typically begins in childhood. Early symptoms of this disorder usually appear between the ages of 5 and 10 years. When parents or physicians may notice that a previously normal child has begun to develop vision problems and seizures. In some cases the early signs are subtle, and may appear in the form of personality and behavioural changes, slow learning, clumsiness, or stumbling. With time, the affected children suffer from mental impairment, worsening seizures, progressive loss of sight and motor skills. Eventually children affected with this disease become blind, bedridden and demented. Batten disease is often fatal by late teens or twenties. Early detection of this disease is possible by an eye scan. Blood and urine tests may be carried out to confirm the diagnosis.

Fabry disease
Fabry disease occurs due to the deficiency of an enzyme which is responsible for the breakdown of a fatty substance. This results in abnormal deposition of fatty substance in blood vessel walls throughout the body. This disease typically manifests in childhood with episodes of pain and burning sensations in the hands and feet. In some individuals a typical rash is seen. Painful episodes maybe brought on by exercise, fever, fatigue, stress or change in weather conditions. Cardiac and renal complications may also begin in childhood. Hence early diagnosis and careful monitoring are necessary. Other symptoms may include an inability to sweat, gastro intestinal disturbances, recurrent nausea and vomiting, dizziness, headache and fever. Fabry disease can be diagnosed based on a number of parameters such as urine analysis, complete blood panel and chest X-ray.

Gaucher disease
Gaucher disease occurs due to accumulation of a certain lipid in the bone marrow, spleen, lungs, liver and sometimes the brain. The most common symptoms of Gaucher disease are enlargement of the liver and spleen, anaemia, nosebleeds, reduced platelets (resulting in easy bruising and long clotting time), bone pain, bone deterioration, bone infractions, often leading to damage to the shoulder or hip joints and osteoporosis. Bone weakening may result in susceptibility to fractures. The course of the disease may vary significantly from patient to patient, showing no obvious symptoms in some or causing excessive damage to the spleen, kidney and skeletal system in others. The disease may also lead to disability and death. In some cases, this disease may increase the risk of multiple myeloma, a slow growing cancer of the bones. Gaucher disease can be detected in its early stages by blood or saliva tests. Also, treatments are available for some forms of this disease.

Pompe's disease
Pompe's disease is a lysosomal storage disease which occurs due to a defect in a particular enzyme involved in the metabolism of glycogen leading to its accumulation in the lysosome. It was the first glycogen storage disease to be clinically reported. As the disease progresses, it causes extensive damage to the muscles and nerves.. Symptoms of the disease may appear at any age from early childhood to late adulthood. It is usually characterized by muscle weakness in the hands and legs, more pronounced  in the feet during walking or running. Weakness in the inter-coastal muscles causes difficulty in breathing while lying down, also leads to enlargement of the heart and other heart problems. Diagnosis of the disease can be done by a simple blood test and can also be reinforced by taking accurate family history. In infants, an X-ray showing an enlarged heart is a definite way of diagnosis.

Sanfilippo disease
Sanfilippo disease results from the lack of an enzyme responsible for the metabolism of long chain sugar molecules. Accumulation of these molecules disrupts cellular function, especially in the brain. The central nervous system is primarily affected. Children experience hyperactivity, loss of speech, mobility and other bodily functions, insomnia, mental retardation, seizures,  cardiac problems and dementia. Other symptoms may include diarrhoea, full lips, coarse facial features, stiff joints, muscle spasms and walking difficulties. The initial symptoms are mild developmental obstacles and first seen between two to six years. As the disease progresses, children typically develop extreme behavioural issues and loose all cognitive skills. Blood tests, urine analysis, echocardiogram and X-rays may be carried out to diagnose the disease. Early detection and prevention may be possible by genetic counselling and prenatal testing.

No definite cures for lysosomal storage diseases have been found yet, but research is in progress to develop methods for treatment of the underlying cause and not just the symptoms associated with the various diseases. However, treatment options such as the bone marrow transplant and enzyme replacement therapy are currently available for certain lysosomal storage diseases. It is hence imperative for the scientific community to study this rare group of disorders in order to treat the people who are suffering from these life threatening conditions.