Screening of Lysosomal Storage Disorders Diseases in Minority Groups

Lysosomes are small, cytoplasmic organelles that contain several acid hydrolase enzymes.
These enzymes break down foreign materials and cellular debris allowing the lysosomes to act
as recycling centers for the cells. Following DNA transcription, lysosomal enzymes are
produced in the endoplasmic reticulum and targeted to lysosomes by specific recognition
markers. If one of the enzymes is absent or if its function is diminished due to either an
altered amino acid sequence of the protein or defective intracellular trafficking, the
macromolecules metabolized by the specific enzyme will gradually accumulate in the lysosomes.
Abnormal substrate storage leads to cellular dysfunction followed by cell death ultimately
manifesting as tissue damage and organ failure.

More than 50 metabolic disorders resulting from defective lysosomal enzyme function have been
described and are classified as lysosomal storage disorders (LSDs). Although individually
uncommon (less than 1 in 100,000), the combined incidence of this group of genetic disorders
is about 1 in 5,000 to 1 in 10,000. The prevalence might be even higher than predicted due to
undiagnosed instances or misdiagnosis of milder cases.

Most of LSDs are inherited in an autosomal recessive manner except two disorders: Fabry
disease and Hunter syndrome, which are X chromosome linked. Two healthy carriers of the same
autosomal recessive disease may have an affected child. Usually the carriers are unaware of
their carrier status prior to screening or until they have a sick child. These disorders are
more common in communities with high consanguinity and where cousin marriages are allowed. In
the case of X-linked diseases, the mutant gene is passed down from one generation to the next
one in a specific way. If a male has an abnormal copy of the specific gene, he will show the
typical presentation of the disease. If a woman has an abnormal copy of the specific gene,
she may develop some milder symptoms of the disease due to random X- inactivation.

Screening for LSDs is performed by measuring enzymatic activity in peripheral blood. The most
cost effective and convenient way is to use dried filter paper blood spots. A positive
screening result has to be followed by a confirmatory enzymatic testing using white blood
cells, plasma or cultured skin fibroblasts and/or DNA mutation analysis. The importance of
screening for LSDs has been recognized by several state governments as these tests are being
included in many newborn screening programs. Although newborn screening helps to identify
patients early on, there is still an unmet need for population screening and for identifying
patients with reversible tissue damage. LSDs cause serious and progressive problems with
multiple body systems. Therapy is available and is promising in most cases. Importantly,
patients with LSDs require thorough management plans for their complex health issues.

Inclusion Criteria:

- To be enrolled in this study the subject must meet the following (inclusion) criteria:

- Subject is greater than or equal to 1 day of age and less than or equal to 100
years of age

- Subject is managed by a physician in the Washington, D.C and Richmond, VA metro
area

- Subject is getting blood work as part of standard clinical care and there is at
least 60 uL blood remained in a tube after all clinical tests were run

Exclusion Criteria:

- subjects must not meet any of the following (exclusion) criteria:

- Absolute contraindication for blood drawing

- Subject cannot be traced back by the referring physician upon a positive
screening result