Acute intermittent porphyria and mental illness – a family study

Abstract

All cases of acute intermittent porphyria (AIP) are believed to be caused by a mutation in the gene encoding for porphobilinogen deaminase, a rate-limiting enzyme in the haem synthetic pathway. This gene has been mapped to the long arm of chromosome 11, a region of the genome that has recently attracted considerable attention as a possible location for genes implicated in major mental disorder. This study was designed to show whether major mental illness co-segregated with acute intermittent porphyria in families where the two conditions are found. The study also investigated the relation between clinical mental symptoms and biochemical parameters of acute intermittent porphyria. The case records of 344 consecutive patients admitted to the Porphyrias Research Group in the Western Infirmary in Glasgow between 1950 and 1988 with acute intermittent porphyria were examined for evidence of psychiatric contact. Of 16 individuals identified, 12 were available for the study. Forty relatives of these 12 probands, including 9 who were asymptomatic carriers of AIP, were interviewed for lifetime history of mental illness and current symptoms. Comparisons were made between 4 groups of patients based on urinary porphyrin levels and erythrocyte enzyme activity; 1) manifest acute intermittent porphyria, 2) latent acute intermittent porphyria, 3) normal relatives and 4) total acute intermittent porphyria (latent and manifest combined). No association was found between AIP and schizophrenia or manic-depressive illness. Only one patient with schizophrenia was found in the sample of 344 case notes, and in 2 families bipolar illness was found but did not segregate with acute intermittent porphyria. The commonest psychiatric diagnosis in patients was generalized anxiety.(ABSTRACT TRUNCATED AT 250 WORDS)

Porphyrins, porphyrin metabolism and porphyrias. I. Update

“…The porphyric encephalopathy may present in various ways, ranging from extreme agitation, insomnia, hallucinosis or frank psychosis to asthenia, anxiety or depression. The patients are often perceived as demanding and troublesome, but it has been questioned whether acute porphyria would account for chronic psychiatric illness [52]. Seizures may occur, sometimes dependent on hypomagnesemia or hyponatremia due to vomiting,¯uid overadministration or inappropriate release of antidiuretic hormone.…”

Environmental Chemical Exposures and Disturbances of Heme Synthesis

“…Accordingly, screening surveys of psychiatric inpatients have reported a relatively high prevalence of individuals with previously unrecognized porphyria (22)(23)(24). One recent study, however, found no significant increase in major psychiatric illness among 344 consecutive patients with AIP (25).…”

Neurological complications of porphyria

“…Porphyria is classified as an organic disease but in some patients psychiatric manifestation can be present, such as anxiety 38 and behavioural disturbances. In some instances family members are aware of the neuropsychiatric corollary and tend to fear this stigmatisation related to the diagnosis.…”