Plasma Psychosine Analysis
Related Gene(s): GALC
Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme galactocerebrosidase (GALC). This deficiency results in the accumulation of galactosylsphingosine (psychosine) and other neurotoxic substrates, leading to the formation of globoid cells and subsequent demyelination throughout the central and peripheral nervous systems. This condition is caused by mutations in the GALC gene.
The early infantile form of Krabbe disease (EIKD) is seen in approximately 1 in 100,000 live births. Affected infants will typically present between 3 and 6 months of age with irritability, hypersensitivity to stimuli, feeding difficulties, spasticity, and seizures. This is generally followed by rapid neurologic deterioration and death before 2 years of age. Pre-symptomatic hematopoietic stem cell transplantation has shown some success in reducing morbidity and mortality associated with EIKD. Later-onset Krabbe disease has an estimated incidence of 1 in 40,000 people and can present anywhere from the first year of life to the seventh decade. The clinical presentation is highly variable and can include muscle weakness, gait disturbances, vision loss, neuropathy, psychomotor regression, and cognitive decline.
Psychosine plays important roles in the pathogenesis of neurological disease. It has been shown to be elevated in patients with active disease and appears to be correlated with the severity of Krabbe disease. The plasma psychosine level in conjunction with the residual GALC activity level may be useful in predicting the presence of disease or disease progression.
Psychosine is extracted from plasma and is fully separated from its isomer glucosylsphingosine and analyzed by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Plasma psychosine is indicated in individuals with
- Any clinical signs and symptoms suggestive of Krabbe disease
- Positive newborn screening findings for Krabbe disease
- Late-onset Krabbe disease for monitoring disease progression
- Blood: 1-2 mL in EDTA tube (lavender top) or sodium heparin tube (green top). Minimum of 0.5 mL is required
- Plasma: 0.5-1 mL. Minimum of 100 μL is required
- Separate plasma immediately and ship frozen plasma on dry ice
- Ship and store frozen until analysis
- 5 days