Serum alpha fetoprotein in Ataxia Telangiectasia: New lessons about an old biomarker

Ataxia Telangiectasia (A-T) is a rare neurodegenerative disease caused by mutations in the A-T Mutated (ATM) gene encoding the ATM protein. No curative treatments are available for A-T. Serum alpha fetoprotein (AFP) is a well known biomarker for A-T, but less is known about changes in serum AFP levels during the course of disease. The aim of this study is to obtain more insight in the serum AFP levels over time in individuals with classic and variant A-T, in order to better define its diagnostic potential. Furthermore, we hope that better understanding of the natural course of serum AFP levels in patients with A-T will contribute that the serum AFP level can be used as a valuable outcome measure in future clinical trials.

In this retrospective cohort study, we collected the initial and all follow-up serum AFP levels from the medical records of individuals (children and adults) with A-T who visit our multidisciplinary A-T outpatient clinic at the Radboud university medical center in Nijmegen, the Netherlands.

In total, 336 serum AFP measurements in 45 individuals with A-T (36 with classic A-T and 9 with variant A-T) were included in this study. All patients showed increased serum AFP levels during the course of disease. In the first two years of life, however, serum AFP levels were found within the range of age-dependent reference values. Individuals with classic A-T showed the most rapid increase in serum AFP levels (on average 26.8 μg/l per year), between 2 and 12 years of life. Their serum AFP levels increased by 19.2 μg/l per year between the ages of 12 and 18 years and stabilized at a level ranging from 34 to 1000 μg/l thereafter. Serum AFP levels in adults with variant A-T (range: 95-680 μg/l) were remarkably similar to the levels in adults with classic A-T and remained stable over time.

Serum AFP is a diagnostic biomarker for A-T, but levels may be normal in exceptional situations, especially in the first two years of life. Nevertheless, serum AFP levels increased over time in individuals with classic A-T until the age of approximately 18 years, when a plateau was reached. Caution is warranted when a rapid increase in serum AFP is observed. No normal AFP levels were observed in individuals with classic A-T over the age of 3 years and in individuals with variant A-T in this cohort.