Autonomic dysfunctions in acute intermittent porphyria

A young woman with acute intermittent porphyria is described. She was admitted in a prolonged attack and had developed a flaccid quadriplegia. During the course she showed various manifestations of the autonomic nervous system, including pupils, gastrointestinal tract, cardiovascular system and others. On admission her pupils were equally mydriatic, and reacted to light sluggishly. Dilation of the pupils was seen when cocaine was instilled, but not when adrenalin. It was suggested that the parasympathetic control of pupils was disturbed. She complained repeatedly abdominal pain, nausea, vomiting, and constipation. However, diarrhea was rarely found. Radiological examinations revealed that her bowel movements were markedly impaired. Sinus tachycardia and elevation of blood pressure were frequently observed with attacks, and they correlated with the clinical course. With tachycardia the coefficient variance of R-R interval was markedly decreased, and large dose of atropine failed to accelerate the heart rate. These indicate that the vagal function was markedly impaired with attacks. The effects of isoproterenol and of propranolol on the heart rate were normal. Phenylephrine and phentolamine changed the blood pressure normally. From these it was concluded that the sympathetic nervous function was not so impaired at the time examined. However, with the elevation of blood pressure plasma and urinary noradrenaline were markedly increased. Other autonomic and related manifestations observed during the course included disorders of sweating, loss of sphincter control, fever of unknown cause and amenorrhea.     

Autonomic neuropathy in acute intermittent porphyria.

Autonomic function was assessed in subjects with acute intermittent porphyria and age- and sex-matched controls using five different bedside tests of cardiovascular reflexes. During the acute attack both parasympathetic and sympathetic tests were impaired, but subsequently improved during remission. Early parasympathetic dysfunction was also detected during remission and in latent asymptomatic acute intermittent porphyria.     

Porphyric neuropathies in an acute intermittent porphyria family

The objective of this study was to investigate two patients with porphyric neuropathy in a family with acute intermittent porphyria. Molecular analysis of the porphobilinogen deaminase (PBGD) gene was performed. We analyzed the clinical course of peripheral neuropathy and serial changes in nerve conduction studies (NCS) of the two patients. We also examined the pathological findings of sural nerve biopsy in one patient. Molecular analysis of the PBGD gene revealed a missense mutation (Arg26His) in exon 2 for two patients and their family members. Distal polyneuropathy was noted in the patients with chronic porphyric neuropathy. In the follow‐up NCS, recovery was relatively poor in the lower limb in one patient with severe polyneuropathy, and NCS evidence of deterioration was found following frequent hormone‐related porphyric attacks in another patient. The sural nerve biopsy showed marked loss of myelinated and unmyelinated fibers in one patient with chronic porphyric neuropathy. In contrast to radial and fibular motor nerves in acute porphyric neuropathy, the sural nerve is vulnerable to involvement in chronic porphyric neuropathy following repeated porphyric attack as seen in the NCS.     

Inappropriate ADH syndrome in a patient with acute intermittent porphyria

A case acute intermittent porphyria is described in which the inappropriate antidiuretic hormone secretion syndrome developed masked by rapidly increasing sensorimotor polyneuropathy.     

Electromyogram and nerve conduction in patients with acute intermittent porphyria

Summary Diminished activity of uroporphyrinogen I-synthetase in the liver and other tissues may be regarded to be the primary genetic deficiency of acute intermittent porphyria (AIP). Increased production and renal excretion of delta-aminolevulinic acid (ALA) und porphobilinogen (PBG) are secondary phenomena. The neuropsychiatric symptomatology of AIP consists of neuropathy, vegetative crises and exogenous psychoses.In this study electromyographic and neurographic investigations were performed on 20 persons with AIP. 16 patients had experienced attacks of AIP, 10 of them including neuropathy. 4 persons showed the biochemical findings of AIP but had not yet had symptoms.In cases with persistent pareses following porphyric neuropathy denervation signs or sequelae were still present. In patients without clinical symptoms and in latent cases there were normal or borderline findings. Motor nerve conduction velocity was mostly decreased in combination with denervation signs and in a range that indicated a primarily axonal nerve lesion and consequent myelin damage rather than primary demyelinization. The mean motor conduction velocity of n. tibialis was somewhat lower in patients with porphyric crises without neuropathy than in latent cases without any clinical crises. The differences were not significant in other nerves. The findings are discussed under consideration of the electrodiagnostic results of other investigations and of neuropathological and clinical data.Herrn Prof. Dr. Richard Jung zum 65. Geburtstag gewidmet     

Safety of fluoxetine treatment in a case of acute intermittent porphyria

Acute intermittent porphyria (AIP) is a metabolic disease characterized by recurrent attacks of neurological and psychiatric dysfunction. It is a rare disorder of heme metabolism that usually presents with abdominal pain, gastrointestinal symptoms and autonomic nervous system disturbances. Exposure to certain drugs, dieting, starvation and infection during pregnancy may precipitate AIP attacks. Psychiatric manifestations of AIP include mood changes, organic brain syndrome and psychosis. Here, we present a 21-year-old female patient with AIP and major depression. She had a caesarean section under general anesthesia with pentothal and her recovery time from anesthesia took longer than usual. She had a blood transfusion because of severe anemia following the operation. Three days after her discharge she was readmitted to the hospital with confusion and seizure. It was her first AIP attack and it started 6 days after caesarean section. Two months after her first attack, we saw her for anxiety and depressive symptoms. She was in severe anxiety and depression and she was put on fluoxetine (20 mg/day liquid form). Following the treatment she did not develop any other porphyria attack. Her symptoms vanished and she improved functionally. She stayed on fluoxetine for 6 months without any new AIP attack. Despite limited data regarding fluoxetine therapy in porphyria patients, it seems to be safe for the treatment of depressive and anxiety symptoms in these patients.     

High prevalence of intermittent acute porphyria in a psychiatric patient population

The authors screened 3,867 psychiatric inpatients for intermittent acute porphyria by use of a spot test to detect diminished activity of the erythrocyte enzyme porphobilinogen (PBG) deaminase. Eighteen individuals so identified also had persistently diminished quantitative activity of PBG deaminase. Eight of these appeared to have intermittent acute porphyria by the added criteria of increased urinary delta-aminolevulinic acid or PBG or a family history of intermittent acute porphyria. The overall prevalence of intermittent acute porphyria was 0.21%, a considerably higher rate than that in the general population. Most of the subjects with the disorder had periods of agitated psychosis and apathetic or depressed withdrawal, with signs of neuropsychological impairment. Neurologic abnormalities were not prevalent.