A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome

Abstract

In cerebral folate deficiency syndrome, the presence of autoantibodies against the folate receptor (FR) explains decreased folate transport to the central nervous system and the clinical response to folinic acid. Autoantibody crossreactivity with milk FR from different species prompted us to test the effect of a milk-free diet. Intervention with a milkfree diet in 12 children (nine males, three females; mean age 6y [SD 4y 11mo], range 1-19y), decreased autoantibody titer significantly from 2.08pmol of FR blocked per ml of serum (SD 2.1; range 0.24-8.35) to 0.35pmol (SD 0.49; range 0-1.32; p=0.012) over 3 to 13 months, whereas FR autoantibody titer increased significantly to 6.53 (SD 6.08; range 0.54-14.07; p=0.013) in nine children who were reexposed to milk for 6 to 14 weeks. In 12 children on a normal diet (eight males, four females; mean age 5y 5mo [SD 4y 1mo], range 1y 6mo-16y 4mo), the antibody titer increased significantly from 0.84pmol of FR blocked per ml (SD 0.39; range 0.24-1.44) to 3.04pmol (SD 1.42; range 0.84-6.01; p=0.001) over 10 to 24 months. Decreasing the autoantibody titer with a milk-free diet in conjunction with folinic acid therapy may be advocated for these patients.

Figure 1

Correlation between blocking folate receptor (FR) autoantibody titer and cerebrospinal fluid (CSF) folate level in patients with cerebral folate deficiency (CFD). Filled circles represent non-CFD patients with normal levels of folate in CSF who tested negative for the autoantibody

Figure 2

(a) Effect of dietary intervention with a milk-free diet followed by re-exposure to milk on the antibody titer of nine patients with cerebral folate deficiency (CFD) with autoantibodies against the folate receptor (FR) protein. The remaining three children who continued on a milk-free diet and whose autoantibody titer remained low are not shown. Each individual is depicted by a symbol and identified by the patient number from Table I. (b) Blocking autoantibody titer in 12 CFD patients on a normal diet containing milk and milk-derived products. Each patient is depicted by a symbol and identified by the patient number from Table II. Inset shows the mean, SEM, and statistical significance (determined by the paired t-test) of the autoantibody titer for all participants in each group.

Figure 3

Cross-reactivity of folate receptor autoantibodies against folate receptor from different species (n=9; mean and SEM). The p values were determined by paired t-test.