LPCBS - Clinical: Lysophosphatidylcholines by LC MS/MS, Blood Spot

Test Catalog

Test Name

Test ID: LPCBS    
Lysophosphatidylcholines by LC MS/MS, Blood Spot

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

Second-tier newborn screen for X-linked adrenoleukodystrophy (X-ALD)

Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request

This test is used as a second-tier newborn screen for X-linked adrenoleukodystrophy (X-ALD).

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

This assay measures C20, C22, C24, and C26 lysophosphatidylcholine (LPC) species in dried blood spots by liquid chromatography-tandem mass spectrometry.

 

Peroxisomes are organelles present in all human cells except mature erythrocytes. They carry out essential metabolic functions including beta-oxidation of very long-chain fatty acids (VLCFA), alpha-oxidation of phytanic acid, and biosynthesis of plasmalogen and bile acids. Peroxisomal disorders include 2 major subgroups: disorders of peroxisomal biogenesis and single peroxisomal enzyme/transporter defects. Peroxisome biogenesis defects such as Zellweger spectrum syndrome are characterized by defective assembly of the entire organelle, whereas in single enzyme/transporter defects such as X-linked adrenoleukodystrophy, the organelle is intact, but a specific function is disrupted. These disorders are clinically diverse and range in severity from neonatal lethal to later onset milder variants.

 

X-linked adrenoleukodystrophy (X-ALD) is a disorder affecting the nervous system, adrenal cortex, and testis. It is the most common of the peroxisomal disorders, affecting 1 in 17,000 to 1 in 21,000 males. At least 50% of all females who are heterozygotes for X-ALD are symptomatic. A defect in the ABCD1 gene is responsible for the disease. X-ALD shows a wide range of phenotypic expressions. The clinical phenotypes occurring in males can be subdivided in 4 main categories: cerebral inflammatory, adrenomyeloneuropathy (AMN), Addison only, and asymptomatic. The first 2 phenotypes account for almost 80% of the patients, while the frequency of the asymptomatic category diminishes with age and it is very rare after age 40. It is estimated that approximately 50% of heterozygotes develop an AMN-like syndrome. Treatment options are hormone replacement therapy, dietary intervention, or hematopoietic stem cell transplantation.

 

Elevations of C24 lysophosphatidylcholine (LPC) and C26 LPC may be indicative of X-ALD. In 2016, X-ALD was added to the US Recommended Uniform Screening Panel (RUSP), a list of conditions that are nationally recommended for newborn screening by the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children. Therefore, measurement of LPCs is a useful second-tier test for newborn screening for X-ALD.

 

Zellweger syndrome spectrum (ZSS) is a continuum of severe disorders affecting the nervous system, vision, hearing, and liver function. Most individuals present in infancy, but adult patients have been identified. The prevalence of ZSS is 1 in 50,000. ZSS follows autosomal recessive inheritance. At least 12 different genes have been implicated in ZSS, with approximately 60% to 70% of mutations occurring in PEX1. The clinical phenotypes include Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD).

 

Individuals with Zellweger syndrome typically die within the first year of life without making any developmental progress. Individuals with NALD or IRD typically present in childhood with developmental delays, vision loss, hearing loss, and have a much slower disease progression. There is no specific treatment for ZSS. Although ZSS disorders are not a primary disease target for testing, this test will detect infants with these disorders.

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.

Analyte

Normal Range (mcg/mL)

C20 Lysophosphatidylcholine

Not applicable

C22 Lysophosphatidylcholine

Not applicable

C24 Lysophosphatidylcholine

< or =0.25

C26 Lysophosphatidylcholine

< or =0.20

Interpretation Provides information to assist in interpretation of the test results

An interpretive report is provided.

 

In females: Elevations of C24 LPC or C26 LPC may be indicative of heterozygosity for X-linked adrenoleukodystrophy (X-ALD), or other forms of peroxisomal disorders.

 

In males: Elevations of C24 LPC or C26 LPC may be indicative of X-ALD or other forms of peroxisomal disorders.

 

Abnormal results are not sufficient to conclusively establish a diagnosis of a particular disease. To verify a preliminary diagnosis based on the analysis, independent biochemical (eg, in vitro enzyme assay) or molecular genetic analyses are required.

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

This test is supplemental and not intended to replace state mandated newborn screening.

 

Test is not intended for metabolic screening of symptomatic patients.

 

Carrier status (heterozygosity) for these conditions cannot be reliably detected.

 

A positive test result is strongly suggestive of a diagnosis but requires follow-up by stand-alone biochemical or molecular assay, which is best coordinated by local genetics providers.

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

1. Hubbard WC, Moser AB, Liu AC, et al: Newborn screening for X-linked adrenoleukodystrophy (X-ALD): validation of a combined liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. Mol Genet Metab 2009;97(3):212-220

2. Haynes CA, De Jesus VR: Improved analysis of C26:0-lysophosphatidylcholine in dried-blood spots via negative ion mode HPLC-ESI-MS/MS for X-linked adrenoleukodystrophy newborn screening. Clinica Chimica Acta, 2012;413(15-16)1217-1221

3. Sandlers Y, Moser AB, Hubbard LE, et al: Combined extraction of acyl carnitines and C26:0 lysophosphatidylcholine from dried blood spots: prospective newborn screening for X-linked adrenoleukodystrophy. Mol Genet Metab, 2012;105(3)416-420