Elsevier

Archives of Medical Research

Volume 31, Issue 4, July–August 2000, Pages 404-408
Archives of Medical Research

Original articles
Prevalence of Acute Intermittent Porphyria in a Mexican Psychiatric Population

https://doi.org/10.1016/S0188-4409(00)00092-8Get rights and content

Abstract

Background

Acute intermittent porphyria is a hereditary error of porphyrin metabolism in which the main metabolic defect is caused by a decrease in porphobilinogen deaminase activity. Previous work has demonstrated a higher prevalence of acute intermittent porphyria in the psychiatric patient population than in the general population. The goal of this study was evaluate 300 psychiatric patients and 150 control subjects to detect acute intermittent porphyria by measurement of porphobilinogen (PBG) deaminase activity in blood.

Methods

Screening for porphobilinogen deaminase activity was carried out by fluorometric measurement of porphyrins synthesized during 1 h in blood and the measurement of delta-aminolevulinic acid and porphobilinogen in urine.

Results

We found two psychiatric patients, one male and one female, with decreased porphobilinogen deaminase activity. When the families of these patients were studied, one brother was found to have an abnormality. Among controls, a woman was found to have the abnormality and her father was found to have typical features of the disease.

Conclusions

These results indicate a prevalence of porphyria in Mexican psychiatric patients similar to controls, and that measurement of PBG deaminase activity is a good tool for defining acute intermittent porphyria carriers.

Introduction

Acute intermittent porphyria (AIP) is a hereditary error of porphyrin metabolism in which the main metabolic defect is caused by a decrease in porphobilinogen deaminase (PBG-D) activity. This enzyme converts porphobilinogen (PBG) to uroporphobilinogen 1, 2. This decrease in its activity occurs in several tissues (3). It is a disease of autosomal-dominant inheritance. The gene for PBG-D has been sequenced and characterized 4, 5; it is located on 11q24 (6) and contains 15 exons. The size of the gene is 10 Kb, of which 1.3 Kb represents coding sequence 7, 8, 9. There are reports of 54 mutations in AIP patients (10).

AIP has become a problem for pharmacogenetics due to the fact that 90% of gene carriers are asymptomatic and in a latent stage. There are several conditions that can trigger a crisis or worsen the already existing disease. Among these conditions are the following: alcohol consumption; use of hormones; diets; infections, and several drugs, the latter being the most frequent cause of acute AIP crisis 11, 12. To date, there are reports of nearly 50 drugs and several other compounds that are known to trigger AIP 13, 14, 15, 16, 17, 18.

AIP is more frequent in women and is experienced almost always after puberty. In some cases, crises are directly related to the menstrual cycle, often present during the premenstrual phase (19). Asymptomatic women have been reported to have a crisis throughout pregnancy (19). During the crisis, women excrete high amounts of delta-aminolevulinic acid (ALA) and PBG. Both are colorless compounds, but when exposed to sunlight and air, PBG polymerizes and forms two chromatic compounds that darken the patient's urine (20).

Symptoms in AIP crisis are related to alterations to the central nervous system (CNS) and, therefore, clinical features will depend largely on the affected areas 21, 22. Up to 5% of crisis are severe enough to require hospitalization and have a fatal outcome (23). Estimates of the frequency of AIP in general populations are not available, but those for the U.S. have been estimated at 5 and 10 per 100,000. In Sweden, Denmark, Ireland, and Western Australia, frequencies range from about 1–8 per 100,000, estimated based on urinary ALA and PBG determinations. Epidemiologic data based on erythrocyte PBG deaminase measurements are not available except within individual families in which relatives have been screened for carrier status (2). Studies in psychiatric populations have revealed a high prevalence of the disease; however, there are only three reports on the prevalence of acute intermittent porphyria in psychiatric populations. Kaelbling et al. (24) screened by means of the Watson-Schwartz reaction without the final butanol extraction step and reported a prevalence of 0.48%. Wetterberg found a prevalence of 0.16% by the quantitative assay of PBG, but only Tishler et al. (25) included the measurements of both PBG deaminase and urinary porphyrins precursors and found a prevalence of 0.21%.

The symptoms of psychiatric patients in AIP are anxiety, restlessness, insomnia, paranoia, depression, auditory hallucinations, and bizarre and persecutory delusions; in some cases, these symptoms—especially depression and anxiety—may become chronic (2).

The aim of this study was to establish the frequency of AIP in a group of Mexican psychiatric patients compared to a control group without apparent psychiatric disorders, as well as the male:female ratio. For this purpose, blood enzymatic activity of PBG-D and urinary qualitative/quantitative measurements of PBG and ALA were performed; based on the measurements of red blood cell PBG, deaminase activity is sensitive and specific to confirm the diagnosis of AIP and allows it to identify latent carriers of the gene defect (26).

Section snippets

Patients and Methods

Three hundred psychiatric patients with different diagnoses were studied. One hundred seventy-one patients were in- patients at the Instituto Nacional de Neurologı́a y Neurocirugı́a Manuel Velasco Suárez in Mexico City. The remaining were out-patients to whom an invitation to participate in the study was sent by mail. Of 577 patients, only 129 responded and accepted to participate. One hundred fifty controls were obtained among altruistic blood donors and hospital employees. We calculated

Results

Patient age averaged 33.6 (±12.5 SD) years with a range of 15–78 years. One hundred sixty-four patients (54.67%) were female and 136 (45.33%) male. Because our institution is a reference center for the entire country, several Mexican states were represented among the patients. Controls had an average age of 31.35 (±8.8 SD) years with a range of 18–60 years. Gender distribution was 41 individuals (27.3%), female and 109 (72.7%), male. As with patients, blood donor controls who were not hospital

Discussion

PBG-D activity values in our population averaged 26.38 (±7.4 SD) for patients and 25.79 (±7.8 SD) for controls. These values are lower than those reported by Sassa et al. (3), which were 35.7 (±8.4 SD), and Magnusen et al. (14), who reported a mean of 40.7 nmol. We decided to adopt a value of <15 nmol of uroporphyrins as abnormal; this cut-off point is ±1.5 times the standard deviation, thus able to detect two patients (and a family member) with AIP, as well as detecting a carrier (and a family

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