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• W2000391704 abstract "Dopamine-β-hydroxylase (DβH) is the enzyme responsible for intraneural conversion of dopamine to norepinephrine. Its deficiency results in failure of norepinephrine synthesis, excessive dopamine release and orthostatic hypotension. We studied a young patient with this deficiency using the currently available methods to assess sympathetic function namely measurement of norepinephrine kinetics, microneurography to assess muscle sympathetic nerve activity (MSNA), and heart-rate spectral analysis. We compared these findings with those in 24 young healthy controls, and 4 patients with peripheral autonomic failure (PAF). Recordings were made in our subject before and after 5 months of treatment with l-threo-3,4-dihydroxyphenylserine (DOPS) (which is converted directly into l-norepinephrine bypassing the DβH enzymatic step); measurements were made at rest in the supine position and after 15 min of 30° head-up tilt. Our subject with DβH deficiency had a high resting nerve firing rate (40.3 bursts/min) compared with the mean value in normal controls (19.3 burst/min), and an appropriate increase in nerve firing rate during tilt. Total body norepinephrine spillover at rest was very low, 38 ng/min, compared with age-matched normals (519 ± 43.3 ng/min, mean ± SEM), and epinephrine secretion was undetectable. Conversely, the plasma concentrations of dopamine, DOPAC, HVA and DOPA were raised. At rest, low-frequency heart-rate variability (0.1 Hz) was absent with preservation of the respiratory-related high-frequency peak. In contrast, the PAF subjects had no detectable muscle sympathetic nerve activity, very low levels of norepinephrine spillover and epinephrine secretion and a reduction in heart rate variability at all frequencies. After 5 months treatment with l-threo-3,4-dihydroxyphenylserine (DOPS) in the DβH deficiency patient there was a dramatic clinical improvement with resolution of the orthostatic symptoms, dramatic reduction in MSNA activity at rest, and return of plasma norepinephrine, norepinephrine spillover, DHPG and MHPG to within the normal range, indicating intraneuronal production of norepinephrine." @default.
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• W2000391704 date "1995-11-01" @default.
• W2000391704 modified "2023-10-18" @default.
• W2000391704 title "Total norepinephrine spillover, muscle sympathetic nerve activity and heart-rate spectra analysis in a patient with dopamine β-hydroxylase deficiency" @default.
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• W2000391704 doi "https://doi.org/10.1016/0165-1838(95)00048-3" @default.
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