Clinical Information

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, 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 disorder (ZSD), are characterized by defective assembly of the entire organelle, whereas in single enzyme/transporter defects, such as X-linked adrenoleukodystrophy (XALD), 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.

XALD 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 male patients. At least 50% of all female patients who are heterozygous for XALD are symptomatic. A defect in the ABCD1 gene is responsible for the disease. XALD shows a wide range of phenotypic expressions. The clinical phenotypes occurring in male patients 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 40 years of age. It is estimated that approximately 50% of heterozygous individuals develop an AMN-like syndrome. Treatment options are hormone replacement therapy, dietary intervention, or hematopoietic stem cell transplantation.

Elevations of C24 LPC and C26 LPC may be indicative of XALD. In 2016, XALD was added to the US Recommended Uniform Screening Panel, 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 XALD.

ZSD are 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 ZSD is 1 in 50,000. ZSD follows autosomal recessive inheritance. At least 12 different genes have been implicated in ZSD, with approximately 60% to 70% of genetic variants 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 ZSD. Although ZS are not a primary disease target for testing, this test will detect infants with these disorders.