Biochemical effect of intravenous arginine butyrate in X-linked adrenoleukodystrophy

To determine the biochemical and clinical effects of intravenous arginine butyrate in X-linked Adrenoleukodystrophy (X-ALD).

Arginine butyrate was intravenously infused over a 4-month period in a patient with the rapid cerebral form of X-ALD. Very long chain fatty acids (VLCFA), complete blood counts, and serum chemistries were monitored, and serial MRI of the brain and clinical neurologic examinations were performed.

All blood chemical and hematologic values remained within the normal range for age throughout the therapy. After completion of the first day of infusion, the C 26:0 value fell from 1.01 microg/mL to 0.445 microg/mL, which is below the mean value for an X-ALD heterozygote. Throughout the remainder of the trial, all C26:0 levels fell below the mean -1 SD for X-ALD hemizygotes (mean, 1.18 microg/mL, 1 SD = 0.53), ranging from 0.321 to 0.565 microg/mL. Despite reduction of the plasma VLCFA, the patient continued to deteriorate neurologically.

Intravenous arginine butyrate resulted in a rapid decrease in plasma VLCFA but no effect on the neurologic progression of the disease in this patient. Additional studies are needed to determine minimum effective dosage and interval, what proportion of patients respond, and whether the agent can prevent neurologic degeneration.