The identification of an LSD can be complex and lengthy. While acute or rapidly progressing cases may be identified more quickly,^[1] often the diseases are slower to progress, and signs and symptoms may be subtle and easily overlooked.^[1] Certain symptoms, especially when appearing in clusters, should alert physicians to the possibility of an LSD as the underlying cause. To learn more see the Presentation and Progression page. However, many of these appear with other more common diseases, leading to delays caused by misdiagnosis. Diagnosis based purely on clinical observations is rarely conclusive;^[2] diagnostic testing is generally required.

The main method of validating a clinical suspicion is enzyme assay, available for most LSDs.^[1] These tests compare enzyme levels in a patient sample (generally blood, urine, or skin fibroblasts) against normal benchmarks. Prenatal testing is often possible,^[1,3] most reliably through amniocentesis (sometimes also by chorionic villus sampling).^[2] Low levels of a particular enzyme confirm the LSD associated with that enzyme defect.^[4] While samples are relatively easy to obtain and results usually take only a few days,^[4] the tests are complex to interpret and must be analyzed by a specialized laboratory.^[1,2]

Enzyme assays are considered the most definitive test,^[1] but they are not available for every LSD. In some cases, other methods may be used, such as brain MRIs, electroretinogram, or biopsy of enlarged tissue.^[1] Mutation analysis can check for a gene mutation known to cause a particular disorder. It is not always conclusive, however, since there are usually several mutations that may cause a particular LSD, and a patient may have an unidentified mutation.^[1]

Most of the LSDs are inherited as autosomal recessive genetic defects (the exceptions are Fabry and MPS II, which are X-linked recessive).^[1] Those who receive a mutated gene from only one parent are carriers, and generally have no or mild clinical manifestations.^[1] Since carriers have one normal gene, they may have normal or near-normal enzyme levels,^[2] so enzyme assays are not reliable. Instead, mutation analysis can be used to identify the faulty gene.

Identifying carriers is important in families of a diagnosed patient, so families can be counseled.^[4] In addition, certain LSDs are more prevalent in certain ethnic and geographic groups, so carrier screening may be valuable for families in these higher-risk populations. For example, Gaucher, Tay-Sachs, and Niemann-Pick are all more common among Ashkenazi Jews, aspartylglycosaminuria has higher prevalence in Finland, and MPS III in the Netherlands.^[1,3] Screening at-risk populations can help lower incidence rates and allow for preemptive disease management. Tay-Sachs screening for high-risk groups began in 1971 and has helped significantly lower the rate of affected births; screening for other diseases is underway as well.^[1]

1. Wilcox, WR. Lysosomal Storage Disorders: The Need for Better Pediatric Recognition and Comprehensive Care. Journal of Pediatrics; May 2004: S3-S14.

2. Muenzer, J. The Mucopolysaccharidoses: A Heterogeneous Group of Disorders with Variable Pediatric Presentations. Journal of Pediatrics; May 2004: S27-S34.

3. Meikle, PJ, et al. Prevalence of Lysosomal Storage Disorders. JAMA; 281: 249-254.

4. Wenger, DA. Insights into the Diagnosis and Treatment of Lysosomal Storage Diseases. Arch Neurol; 60: 322-328.