Archives

  • 2018-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • br Materials and methods br Results br Discussion br

    2020-03-04


    Materials and methods
    Results
    Discussion
    Conflict of interest
    Introduction Dopamine-β-hydroxylase (DβH) deficiency is a Dequalinium Chloride rare autosomal recessive disorder characterized by the congenital absence of DβH, the enzyme converting dopamine to noradrenaline in sympathetic nerve terminals and the adrenal medulla (Senard and Rouet, 2006, Robertson and Garland, 2003). The disease is clinically characterized by primary autonomic failure with severe orthostatic hypotension (OH) possibly mimicking a peripheral autonomic neuropathy (PAN), but cardiovascular reflexes together with cardiac innervation study and plasma catecholamine titration showed typical findings. Furthermore, skin biopsy and microneurography evaluate peripheral sympathetic fibers to differentiate adrenergic from cholinergic fibers thereby helping to identify selective abnormalities of a sympathetic subdivision (Donadio et al., 2012a, Donadio et al., 2012b). We describe a patient with hereditary neuropathy with liability to pressure palsies (HNPP) due to a Dequalinium Chloride of the PMP22 gene who complained of chronic OH. The combination of skin biopsy and microneurography excluded a diffuse PAN and disclosed a selective peripheral adrenergic dysfunction supporting a DβH deficiency which was suggested by typical findings of cardiovascular reflexes, plasma catecholamine titration and MIBG cardiac innervation. The DβH deficiency was then confirmed by the genetic analysis demonstrating two novel mutations in the DβH gene (Bartoletti-Stella et al., 2015).
    Case report We describe a 37-year-old man with a family history positive for HNPP due to a deletion of the PMP22 gene (father). The patient (hereafter named proband) complained of fatigue, light-headedness, bilateral blurred vision and increased perspiration arising on assuming or maintaining the upright position and ceasing with sitting or lying down from age 12. At the age of 25years the proband was admitted to hospital following partial occlusion of the left central retinal vein and autoimmunity screening was positive for anti-nuclear antibodies. During his hospital stay, the proband was found to have neurogenic OH. At age 28, episodic paresthesias and motor impairment of the right leg began either spontaneously or after secondary compressions. Due to his positive family history the patient underwent genetic analysis demonstrating the same PMP22 gene mutation as his father. No OH was reported in other family members. We investigated the proband for the chronic OH, suspecting an acquired (i.e. autoimmune) PAN because of the absence of familiarity and the positivity for anti-nuclear antibodies. Extensive serum screening for known causes of peripheral neuropathy did not disclose any abnormalities except the confirmation of anti-nuclear antibody positivity. Head-up tilt at 65° for 8′30″ showed severely symptomatic orthostatic hypotension (Δsystolic blood pressure-ΔSBP: −61mmHg; Δdiastolic blood pressure-ΔSBP: −35mmHg; with a compensatory heart rate increase-ΔHR: 30bpm). The expected blood pressure (BP) overshoot during phase 4 of Valsalva Maneuver (VM) (post-release) was absent and HR variability was reduced. A modest respiratory arrhythmia was present during deep breathing (Δinspiratory-expiratory: 10bpm). Isometric handgrip increased BP (ΔSBP: 20mmHg; ΔDBP: 15mmHg; ΔHR: 14bpm) whereas the cold pressor stimulus did not raise BP (ΔSBP: 4mmHg; ΔDBP: 0mmHg; ΔHR: −4bpm). These results suggested a selective cardiovascular noradrenergic failure with preserved cardiovagal responses. Catecholamine plasma titration confirmed very low noradrenaline (6pg/ml; normal values 182±40pg/ml) with high dopamine levels (181pg/ml; n.v. up to 70pg/ml). Cardiac 123I-MIBG scintigraphy showed normal myocardial uptake [early (15min) and delayed (4h) heart-to-mediastinum uptake ratios were 1.79 and 2.07; n.v. >1.55]. Data of autonomic nervous system screening tests together with plasma catecholamine titration and preserved sympathetic MIBG innervation supported a DβH deficiency which was confirmed by the genetic analysis disclosing two novel mutations in the DβH gene (Bartoletti-Stella et al., 2015). The proband was put on l-threo-dihydroxyphenylserine (Droxidopa) 600mgt.i.d. following in-ward titration and his orthostatic intolerance has very much improved ever since (Bartoletti-Stella et al., 2015). To further characterize the peripheral autonomic dysfunctions the proband underwent skin biopsy and microneurography. As controls we performed the same tests in an age-matched healthy male (hereafter named control) and an age-matched male patient with OH due to an autoimmune PAN (Sjogren disease: hereafter named control patient). The procedures used were approved by the local Human Ethics Committee. All subjects gave their written informed consent to the study.