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Interpretive Handbook

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Test 60719 :
Lysozyme (LYZ) Gene, Full Gene Analysis

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The systemic amyloidoses are a number of disorders of varying etiology characterized by extracellular protein deposition. The most common form is an acquired amyloidosis secondary to multiple myeloma or monoclonal gammopathy of unknown significance (MGUS) in which the amyloid is composed of immunoglobulin light chains. In addition to light chain amyloidosis, there are a number of acquired amyloidoses caused by the misfolding and precipitation of a wide variety of proteins. There are also hereditary forms of amyloidosis.

 

The hereditary amyloidoses comprise a group of autosomal dominant, late-onset diseases that show variable penetrance. A number of genes have been associated with hereditary forms of amyloidosis, including those that encode transthyretin, apolipoprotein AI, apolipoprotein AII, fibrinogen alpha chain, gelsolin, cystatin C and lysozyme. Apolipoprotein AI, apolipoprotein AII, lysozyme, and fibrinogen amyloidosis present as non-neuropathic systemic amyloidosis, with renal dysfunction being the most prevalent manifestation.

 

LYZ-related familial visceral amyloidosis presents clinically with significant renal impairment. The renal dysfunction occurs at an early age and, in the absence of treatment, results in renal failure. Other manifestations of LYZ-related familial visceral amyloidosis include gastrointestinal involvement, cardiac disease, Sicca syndrome, and propensity towards petechiae, hemorrhage and hematoma, including hepatic hemorrhage. The bleeding tendency associated with LYZ-related familial visceral amyloidosis has included rupture of abdominal lymph nodes. Neuropathy is not a feature of LYZ-related familial visceral amyloidosis.

 

Due to the clinical overlap between the acquired and hereditary forms, it is imperative to determine the specific type of amyloidosis in order to provide an accurate prognosis and consider appropriate therapeutic interventions. Tissue-based, laser capture tandem mass spectrometry might serve as a useful test preceding gene sequencing to better characterize the etiology of the amyloidosis, particularly in cases that are not clear clinically.

Useful For Suggests clinical disorders or settings where the test may be helpful

Confirming a diagnosis of lysozyme (LYZ) gene-related familial visceral amyloidosis

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A small percentage of individuals who have a diagnosis of lysozyme (LYZ) gene-related familial visceral amyloidosis may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of LYZ-related familial visceral amyloidosis. For carrier testing, it is important to first document the presence of a LYZ gene mutation in an affected family member.

 

In some cases, DNA alterations of undetermined significance may be identified.

 

Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

 

A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

 

Mutations in other genes, such as those encoding transthyretin, fibrinogen alpha chain, apolipoprotein AII, gelsolin, and others, have been shown to cause other forms of familial amyloidosis. Abnormalities in these genes are not detected by this assay.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Benson MD: The hereditary amyloidoses. Best Pract Res Clin Rhematol 2003;17:909-927

2. Benson MD: Ostertag revisited: The inherited systemic amyloidoses without neuropathy. Amyloid 2005;12(2):75-87

3. Shiller SM, Dogan A, Highsmith WE: Laboratory Methods for the Diagnosis of Hereditary Amyloidoses. In Amyloidosis-Mechanisms and Prospects for Therapy. Edited by S Sarantseva. InTech, 2011. pp 101-120


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