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.

Neuronal Source of Plasma Dopamine

“…In POTS, increased plasma concentrations of both DA and NE are consistent with increased overall sympathetic nerve traffic, decreased neuronal reuptake, or both (38, 39). Finally, all patients with familial dysautonomia have increased plasma DA:NE ratios (40), which, given the present findings, suggests augmented release from vesicles containing newly synthesized NE. Enhanced understanding about sources and meaning of plasma DA concentrations, in the context of data about plasma concentrations of other catechols, may provide biomarkers with which to diagnose and track progression of diseases and monitor effects of treatment.…”

CSF Catecholamine Profile in Subarachnoid Hemorrhage Patients with Neurogenic Cardiomyopathy

“…Similarly, it has been proposed that CSF levels of DOPA may reflect central catecholamine biosynthetic capacity [16], and that CSF DOPAC levels may provide an estimate of overall central adrenergic transmission [17]. The ratio of NE to DHPG (the major CNS metabolite of NE) [14] has been utilized as an index of active noradrenergic function by comparing the relative activity of NE release to uptake [18,19]. Elevated ratios have been observed in plasma during physical exertion [19][20][21], and in the CSF following sympathetic disinhibition [16], and decreased ratios have been noted in animals exposed to sympatholytics [22].…”

Deficient vesicular storage: A common theme in catecholaminergic neurodegeneration

“…The disease is thought to be associated with arrested development of sympathetic noradrenergic neurons, with neurodegeneration progressing during adult life [7]. We found no literature about the status of putamen dopaminergic innervation in FD.…”