Lysosomal storage diseases are genetic disorders resulting from mutations in genes coding for proteins involved in the degradation of normal body compounds, including lipids, proteins and complex carbohydrates. While most lysosomal disorders are caused by defects in genes coding for enzymes, some are caused by defects in genes coding for transport proteins, activator proteins, protective proteins or enzymes involved in the processing of lysosomal enzymes or substrates. The lack of one of these proteins leads to the accumulation of undegraded compounds which can disrupt the normal functioning of the cells involved. Most of these disorders are autosomal recessively inherited, however a few are X-linked recessively inherited, such as Fabry disease and Hunter syndrome (MPS II).

This laboratory can test for those diseases preceded by an asterisk

• *GM1 gangliosidoses, Morquio B
• *GM2 gangliosidoses (O, B, AB, B1 variants)
• Niemann-Pick disease (*A,*B, and C)
• *Gaucher disease
• *Krabbe disease
• *Metachromatic leukodystrophy (arylsulfatase A and SAP-1 deficient)
• *Wolman disease (cholesterol ester storage disease)
• *Fabry disease
• Farber disease
• *Mucopolysaccharidosis I (Hurler and Scheie syndromes)
• Mucopolysaccharidosis II (Hunter syndrome)
• Mucopolysaccharidosis III (Sanfilippo syndrome A, *B, C, D)
• Mucopolysaccharidosis IV (Morquio syndrome A, *B)
• *Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)
• *Mucopolysaccharidosis VII (β-glucuronidase deficiency)
• *Fucosidosis
• *α-Mannosidosis
• *β-Mannosidosis
• *Galactosialidosis
• *Mucolipidosis I (Sialidosis)
• *Mucolipidoses II and III (I-cell disease)
• Mucolipidosis IV
• *Sialic acid storage disease
• *Sialuria (not a lysosomal storage disorder)
• *Multiple sulfatase deficiency
• Aspartylglucosaminuria
• Cystinosis
• *Pompe disease
• Pycnodysostosis
• Schindler disease
• Neuronal ceroid lipofuscinosis

There is great variability in the clinical features of these different diseases. Symptoms can begin before birth (e.g. non-immune fetal hydrops) or can become obvious in the 90th decade (e.g. Gaucher disease). Many young patients present with developmental delay or regression of learned skills, spasticity, ataxia, abnormal tone or seizures, while others present with evidence of liver and/or spleen enlargement, bone or eye abnormalities, skin lesions, or facial coarsening, with or without a neurological component. A number of adolescent and adult patients with weakness, psychosis and mental deterioration have been diagnosed with a lysosomal storage disease.

If clinical findings with or without other supporting tests (e.g. MRI, bone marrow biopsy) are suggestive of a lysosomal disease, the simplest and most definitive test is a screen of lysosomal enzymes selected based upon the patient’s history. This can be performed by sending us 4-6 ml of a heparinized blood sample in an insulated box by overnight delivery, accompanied by a clinical summary of the patient. As stated above, we will perform all of the tests available in this laboratory that are indicated by the clinical information sent. Almost all testing for patients and carriers can be done using leukocytes isolated here from whole blood. Tests for some diseases such as sialidosis, may require studies in cultured skin fibroblasts. After diagnosing over 5000 patients, we are well aware of the variant patients who do not fit the textbook description of a given disease. We will therefore provide suggestions for additional testing if our results indicate a diagnosis not covered by the tests available using the sample received.

The majority of patients are initially screened by enzyme assays which is the most efficient method to arrive at a definitive diagnosis. In some families where the disease-causing mutation(s) is known and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders. One such disorder is metachromatic leukodystrophy where testing for the so-called pseudodeficiency allele and the two most common disease-causing mutations can be quickly performed. Also, patients found to have Krabbe disease may be tested for the common 30 kb deletion.

We encourage carrier testing for parents of patients we have diagnosed in this laboratory in order to obtain obligate carrier values for these diseases. There is no charge for testing parents of patients diagnosed in this laboratory.

Recent developments in the treatment of these diseases have been made. For some diseases treatment is limited to symptomatic management, however new therapies are being developed. These include bone marrow or umbilical cord stem cell transplantation which are being performed at specialized centers for a number of these diseases. Also, enzyme replacement therapy is either in use or under investigative trial for at least twelve lysosomal disorders. In addition, substrate reduction therapy, a method used to decrease the accumulation of storage material is currently being evaluated for some of these diseases. Furthermore, pharmacological chaperone therapy, a technique used to stabilize the defective enzyme produced by the patients, is being examined for certain of these disorders. Gene therapy for a few of these disorders is in clinical trials. In most cases the chosen treatment simply slows the course of the disease; therefore, it is critical to make a specific diagnosis in a patient as early as possible in order for the selected treatment to have its maximum effect.