Porphyrias are inborn errors of metabolism in which specific enzyme defects exist in the heme synthesis pathway. Chester porphyria is a unique type of porphyria, with the clinical picture of acute intermittent porphyria (AIP) and the biochemical defects of both acute intermittent porphyria and variegate porphyria (VP).[1]
The first description of Chester porphyria is from a clinical observation made in 1963 by an anesthetist, Zorka Bekerus, in Chester, England (hence the name Chester porphyria). The index case, Peter Dobson, was a salmon fisherman born in 1867 in Chester.[2, 3] Numerous family members had the condition, and the family had coined the term Dobson's complaint to describe the mysterious illness.[4, 5]
Chester porphyria does not conform to any of the recognized types of acute porphyria (see image below).
View Image | This schematic diagram of biochemical abnormality shows the sites of enzymatic defects of the various porphyrias on the left side of the diagram and t.... |
The urine porphyrin excretory pattern varies from the pattern of acute intermittent porphyria to variegate porphyria. Chester porphyria exhibits reduction in enzymatic activity of both porphobilinogen deaminase (an enzyme with reduced activity in acute intermittent porphyria) and protoporphyrinogen oxidase (an enzyme with reduced activity in variegate porphyria). Chester porphyria manifests with attacks of neurovisceral dysfunction common to all acute porphyrias. Unlike in variegate porphyrias, cutaneous photosensitivity is not a feature of Chester porphyria.
Genetic studies have linked the Chester porphyria gene to chromosome arm 11q.[6] Precipitating factors of Chester porphyria attacks include the following drugs:
Other precipitating factors are as follows:
The frequency of Chester porphyria is low, and it is only described in the city of Chester, England.
The mortality rate of Chester porphyria is high. Morbidity is significant. Many members of the Chester family were afflicted with hypertension and renal disease. Significant morbidity is associated with painful porphyric crises in patients affected with Chester porphyria. Tracing of the ancestry of the Chester family shows that 14 members had peripheral motor neuropathy; 6 of the 14 developed bulbar palsy, and 4 died as a result.[2, 3]
Complications of Chester porphyria include the following:
Genetic counseling and discussion about Chester porphyria are essential components of clinical management.
Patients with Chester porphyria may present with the following history:
Patients with Chester porphyria may present with the following physical findings:
Skin manifestations are not seen in Chester porphyria.
Laboratory workup for Chester porphyria includes the following:
Currently, no cure exists for Chester porphyria. The goal of management is to avoid precipitating factors in cases of suspected porphyrias. Treatment is symptomatic. Genetic counseling and understanding the disease and its manifestations may be helpful for family members.
Patients with Chester porphyria are at risk of an acute attack of porphyria at the time of surgery. This is because of stress, metabolic abnormalities, and certain drugs used during surgery.
This schematic diagram of biochemical abnormality shows the sites of enzymatic defects of the various porphyrias on the left side of the diagram and the dual enzyme abnormality of Chester porphyria (deficiency of porphobilinogen deaminase [PBGD] and protoporphyrinogen oxidase) on the right. ALA = delta-aminolevulinate; COPRO = copro-porphyrin; HMB = hydroxymethylbilane; HMB-S = hydroxymethylbilane synthase; PROTO = protoporphyrin; URO = uroporphyrin.
This schematic diagram of biochemical abnormality shows the sites of enzymatic defects of the various porphyrias on the left side of the diagram and the dual enzyme abnormality of Chester porphyria (deficiency of porphobilinogen deaminase [PBGD] and protoporphyrinogen oxidase) on the right. ALA = delta-aminolevulinate; COPRO = copro-porphyrin; HMB = hydroxymethylbilane; HMB-S = hydroxymethylbilane synthase; PROTO = protoporphyrin; URO = uroporphyrin.