Lysosomal Storage Disease


BACKGROUND:

Lysosomal storage diseases are a group of genetic disorders resulting from the inadequate intralysosomal degradation of intra- and extra-cellular (phagocytosed) complex chemicals including proteins, carbohydrates, and lipids. While the causes of these diseases are variable, many of them result from the lack of a specific lysosomal enzyme responsible for one step in the sequential degradation of complex carbohydrates and glycolipids. The activity of the enzyme can often be measured in an easily obtained tissue sample, such as leukocytes, serum, or cultured skin fibroblasts, using commercially available synthetic or natural substrates.

INCIDENCE:

The combined incidence of lysosomal storage disease is probably greater than 1 per 5,000 live births, while 4-5 percent of the general population can be presumed to be carriers of the trait for one or another of these diseases.

INDICATIONS FOR TESTING:

A clinical history of the patient is required by the laboratory so the appropriate tests can be performed for diagnosis. A majority of the cases sent to the laboratory fall into four categories:

  • developmental delay and/or regression of previously learned skills from birth to 10 years;

  • seizures with few additional problems;

  • infants and adults with coarse facial features with or without visceral and CNS findings;

  • children and adults with unexplained organomegaly.

In addition, carrier testing can be performed in the appropriate cases. For example, the parents of a child diagnosed with a lysosomal disorder may be tested because

  • it helps confirm the diagnosis in the affected offspring;

  • it provides the laboratory with the enzyme levels in obligate carriers who may later desire prenatal testing;

  • it provides enzyme values that could help with the correct assignment of other family members requesting testing.

Carrier testing may also be requested by individuals with a relative who died with a confirmed or highly suggestive clinical diagnosis.

PROCEDURE:

Assays utilizing fluorometric, spectrophotometric, or radioactive substrates are performed for the appropriate enzymes.

SAMPLE REQUIREMENTS:

Serum: 5-10cc of blood drawn in a red top vacutainer tube. This tissue is not appropriate for all enzyme testing.

Leukocytes: 5-10cc of blood drawn in a purple top (EDTA) vacutainer tube. In most cases for initial screening, this is the tissue of choice.

Skin fibroblasts: Fibroblast cultures are usually started from forearm skin biopsies. Usually two T-25 flasks of cultured skin fibroblasts are required.

In addition, amniotic fluid cells can be sent to the laboratory for prenatal diagnosis of some disorders.

INTERPRETATION:

In most cases, low or absent enzyme activity may indicate a lysosomal enzyme disorder. The results are compared to reference ranges compiled by the laboratory to diagnose the disease state or carrier status of the patient.

GENETIC COUNSELING:

Genetic counseling is available to families faced with the diagnosis of a rare storage disorder.

 

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