Plasma catechols in familial dysautonomia: a long-term follow-up study

Abstract

This study tested whether familial dysautonomia (FD) involves progressive loss of noradrenergic nerves. Plasma levels of catechols, including dihydroxyphenylglycol (DHPG), norepinephrine (NE), dopamine (DA), and DOPA, were measured in 7 adult patients with FD and 50 healthy control subjects. FD patients were re-tested after a mean follow-up period of 13 years. Compared to controls, FD patients had low plasma levels of DHPG (P < 0.001), high DOPA and DA levels (P = 0.01, P = 0.0002), and high NE:DHPG (P < 0.0001), DA:NE (P = 0.0003), and DOPA:DHPG (P < 0.0001) ratios. At follow-up there were no changes in plasma levels of individual catechols; however, there were further increases in DOPA:DHPG ratios (mean 24 +/- 7%, P = 0.01). In FD, plasma catechol profiles are sufficiently stable, at least over a decade, to be used as a biomarker of disease involvement. An increasing DOPA:DHPG ratio suggests slight but consistent, progressive loss of noradrenergic neurons.

Fig. 1

Individual values for the ratio of plasma dihydroxyphenylalanine (DOPA): dihydroxyphenylglycol (DHPG) as a function of plasma dopamine (DA):norepinephrine (NE) in control subjects (white circles), familial dysautonomia patients upon initial evaluation (gray circles), and familial dysautonomia patients after an interval of 13 years (black circles). Dashed lines placed to emphasize that all familial dysautonomia patients had both high DOPA:DHPG and high DA:NE ratios at both testing times, a finding not observed in any control subjects correlated positively with DA:NE ratios (P = 0.69, P < 0.0001).

Fig. 2

Individual values for the ratio of plasma dihydroxyphenylalanine (DOPA): dihydroxyphenylglycol (DHPG) in familial dysautonomia patients upon initial evaluation and after an interval of 13 years. Horizontal bars indicate mean values. Gray zone indicates values within 2 standard deviations of the control mean value. Note that all familial dysautonomia patients had an initial DOPA:DHPG ratio more than 2 standard deviations above the control mean and that the patients had a further increase in the DOPA:DHPG ratio at follow-up