DIAGNOSIS & SCREENING
Since newborns are not typically screened for Lysosomal Disease, detecting it is very difficult and usually occurs once symptoms become present in an infant. As with so many illnesses, early diagnosis is crucial to reduce the severity of symptoms and to start treatment as early as possible.

Physical Diagnosis
Detecting Lysosomal Disease can be challenging for a number of reasons. However, there are certain hallmark signs and symptoms to pay special attention to in your child, particularly, if one or more are present. They are as follows:
• Unusual facial features, often accompanied by an enlarged tongue
• Cloudy film over the eyes
• Purplish to blue skin rash
• Extended belly or specific bulges on the abdomen, which could indicate an enlarged organ
• Short in stature or a failure to develop normally
• Muscle weakness, uncoordinated muscle control, or a decrease in fine motor skills

Biochemical Diagnosis
If Lysosomal Disease is suspected, an enzyme assay is performed which measures the amount of a certain enzyme in blood, urine, or tissue specimens. The amount of the enzyme is then compared to normal enzymatic standards to determine if a disorder is present. If levels are low, a disorder is then confirmed. Prenatal diagnosis is also done by enzyme assays sampling the amniotic fluid. Although enzyme assays are highly accurate, there are not available for all lysosomal disorders. Other methods such as MRI’s, electroretinogram, or a biopsy can also be performed to confirm diagnosis.

Genetic Diagnosis and Screening
Genetic counseling is essential to educate patients and their families on the disorder inheritance, risk analysis, and to support them with counseling. With the exception of Fabry disease and Mucopolysacchariodosis (MPS) type II, all Lysosomal disorders are inherited as autosomal recessive genetic mutations.
Since certain disorders are more prevalent in select ethnic populations, genetic screening can help identify the carriers, reduce the incidence of the disorder, and hasten disease management.

 
TREATMENT:
Given the vast number of lysosomal disorders that have been identified, available treatment options vary widely according to the specific disorder and its severity. Lysosomal Disease is treated using a comprehensive approach that focuses on alleviating the symptoms of the disorder and, if there is a disease-specific treatment, implementing those modes of treatment as well.
Treatment options have increased greatly, largely due to genetic therapies. Since treating the symptoms does not cure the disorder, research has instead focused on replacing the missing enzyme through procedures like gene therapy, the replacement of defective genes with normal genes, and enzyme replacement therapy (ERT).

ERT involves intravenously infusing a synthesized enzyme into the bloodstreams of individuals who are lacking that particular enzyme. The enzyme then works within the cells of the body. Enzymes are currently available for Gaucher’s disease, Fabry’s disease, Hurler’s syndrome, and Pompe’s disease. But there are drawbacks with ERT. It is very costly, at approximately $200,000 per year to administer the weekly injections. Furthermore, since the enzyme does not cross the brain, mental retardation associated with some of the lysosomal disorders cannot be alleviated. Last, the long-term effects of ERT are still unknown.

Another disease-specific treatment is hematopoietic stem cell transplant (HSCT). In this procedure, healthy stem cells, typically from the bone marrow, are transplanted into the individual in order to create the missing enzyme in the body. This procedure does cross the blood/brain barrier and, therefore, can treat mental disabilities that exist in certain lysosomal disorders. But this treatment poses problems, such as transplant rejection, along with disabling side effects.
The research currently underway for using gene therapy as a successful treatment for Lysosomal Disease gives further promise for patients and physicians. Gene therapy involves inserting a normal copy of a gene into the individual’s cells in order to produce the proper enzyme. Even though gene therapy is still in its infancy, scientists and doctors are hopeful that it will one day treat all forms of Lysosomal Disease.

To view a detailed description of individual lysosomal disorders, see the List of Disorders on our Web site.