LC–MS/MS Dried Blood Spot Test for Galactosemia

Galactose-1-phosphate is a substance that doctors measure in the blood to diagnose galactosemia, an inherited condition in which the body cannot properly process a sugar called galactose, and to check how well treatment is working. The test is normally done on red blood cells, which means drawing a fairly large amount of blood and putting the sample through a lot of hands-on preparation in the laboratory.

To make things easier, researchers at the Mayo Clinic’s Biochemical Genetics Laboratory in Rochester, Minnesota, developed and tested a new method that measures this substance from dried blood spots: just a few drops of blood dried on a card. The method uses liquid chromatography–tandem mass spectrometry (LC–MS/MS) to separate the components of a sample and then identify and measure them precisely. The team published their work in the journal Molecular Genetics and Metabolism.¹

What Is Galactosemia, How Is It Treated, and What Are Its Different Forms?

Galactosemia is an inherited condition caused by a missing or faulty enzyme the body needs to break down galactose, a sugar found in milk. It affects many parts of the body, and without treatment it can make babies seriously ill or even be fatal. Cutting lactose (milk sugar) out of the diet works well to treat or prevent the dangerous illness that can strike in the first weeks of life. Even so, sticking to the diet long-term does not prevent every health problem linked to the condition.^2,3

Classic galactosemia is the most common form, but there are three rarer types, each caused by a problem with a different enzyme involved in processing galactose: galactokinase deficiency (an autosomal recessive disorder that causes cataract formation in children not maintained on a lactose-free diet), UDP-galactose-4′-epimerase deficiency (which was first thought to come in two forms, a harmless one affecting only blood cells and a serious one affecting the whole body, but researchers later found it actually ranges along a spectrum from mild to severe), and galactose mutarotase deficiency (an inborn error of galactose metabolism that presents in the neonatal period). These are also treated by limiting galactose in the diet. Because they are less common and newborn screening does not reliably pick them up, they are not the primary focus of screening programs.^4-6

How Was the Dried Blood Spot Test Validated?

Before using the test with patients, the team checked how well it performed. They looked at whether it measured accurately across a range of levels, gave consistent results when repeated, and held up over time. They also found the smallest amounts it could detect and reliably measure, and the normal range of values in people without the condition.¹

To see how the new test compared with the standard one, they took two kinds of samples from patients with galactosemia who were coming in for regular check-ups. One was a dried blood spot (a few drops of blood dried on a card), and the other was a red blood cell sample, which is what’s normally used. They measured a substance called galactose-1-phosphate in both.¹

How do the Test’s Results Compare with the Standard Red Blood Cell Test for Galactosemia Monitoring?

The test could detect very small amounts of this substance, and the normal level in healthy people was found to be 1.0 mg/dL or below. Results from the dried blood spots matched the red blood cell results well overall, but they consistently came out about 20% lower. Because of this, the usual treatment target couldn’t simply be carried over. Using paired samples from 65 treated patients, the team set a separate target for dried blood spots of below 4 mg/dL, compared with below 5 mg/dL for red blood cell samples.¹

In short, dried blood spot testing is a dependable alternative to the standard test. It needs less blood, is easier to collect and mail, and the samples last longer. However, because the results run lower, doctors need to use the dried-blood-spot-specific target when interpreting them.¹

Read More on Similar Subjects
Monitoring Antibiotic Levels in ICU Patients Using Dried Blood Spot Analysis with UHPLC-MS/MS

References

1. Kent, N. A.; Bolster, M. T.; Schultz, M. J. et al. Measurement of Galactose-1-phosphate in Dried Blood Spots by LC-MS/MS: Method Characteristics and Therapeutic Range. Mol Genet Metab. 2026, 149 (4), 110295. DOI: 10.1016/j.ymgme.2026.110295
2. Berry, G. T. Classic Galactosemia and Clinical Variant Galactosemia. in: GeneReviews; Adam, M. P.; Bick, S.; Mirzaa, G. M, et al. Eds. University of Washington, 2000. https://www.ncbi.nlm.nih.gov/books/NBK1518/
3. Fridovich-Keil, J. L.; Berry, G. T. Pathophysiology of Long-term Complications in Classic Galactosemia: What We Do and Do Not Know. Mol Genet Metab. 2022, 137 (1-2), 33-39. DOI: 10.1016/j.ymgme.2022.07.005
4. OMIM (Online Mendelian Inheritance in Man) website. https://omim.org/ (accessed 2026-10-28)
5. Pasquali, M.; Yu, C.; Coffee, B. Laboratory Diagnosis of Galactosemia: A Technical Standard and Guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2018, 20 (1), 3-11. DOI: 10.1038/gim.2017.172
6. van Konijnenburg, E. M. M. H.; Radenkovic, S.; Koop, K. et al. Rethinking Newborn Screening: A Case of GALM Deficiency. Int J Neonatal Screen. 2025, 11 (2), 25. DOI: 10.3390/ijns11020025