Chester Porphyria

Practice Essentials

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]

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Background

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]}

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Pathophysiology

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.

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Etiology

Genetic studies have linked the Chester porphyria gene to chromosome arm 11q.^[6] Precipitating factors of Chester porphyria attacks include the following drugs:

• Barbiturates
• Aluminum hydroxide
• Tricyclic antidepressants
• Alcohol

Other precipitating factors are as follows:

• Smoking
• Surgery
• Metabolic abnormalities such as hyponatremia (also listed as a complication)

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Epidemiology

The frequency of Chester porphyria is low, and it is only described in the city of Chester, England.

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Prognosis

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:

• Malignant hypertension
• Renal failure
• Intracerebral hemorrhage
• Bulbar palsy
• Retinal hemorrhage
• Hyponatremia (also listed as a precipitating factor)
• Peripheral neuropathy
• Myopathy
• Coma and death

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Patient Education

Genetic counseling and discussion about Chester porphyria are essential components of clinical management.

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History

Patients with Chester porphyria may present with a history characteristic of acute intermittent porphyria, which includes the following^{[5, 7]} :

• Abdominal pain
• Constipation and vomiting
• Headache
• Seizures
• Paralysis
• Psychological disturbance
• Palpitations
• High blood pressure

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Physical Examination

Patients with Chester porphyria may present with the following physical findings:

• Elevated blood pressure, consistent with hypertension
• Motor neuropathy, as suggested by flaccid paralysis
• Evidence of psychosis (delusion, hallucinations)^[8]
• Tachyarrhythmias
• Epilepsy
• Kidney failure

Skin manifestations are not seen in Chester porphyria.

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Laboratory Studies

Laboratory workup for Chester porphyria includes the following:

• Urine studies for porphyrins are recommended when an acute attack of porphyria is suspected clinically.^[9]
• Genetic studies can be performed in suspected cases.

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Approach Considerations

Currently, no cure exists for Chester porphyria. The goal of management is to avoid precipitating factors in cases of suspected porphyrias. Treatment is symptomatic and includes supportive care with IV fluids and pain management. Treatments that are known to be effective in acute intermittent porphyria and variegate porphyria are expected to benefit patients with Chester prophyria.^[10]  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.

Eating a balanced diet is important in maintaining health for patients with chronic medical conditions. Nutritional counseling can assist in identifying triggers and potential dietary support to prevent attacks, and maintain weight during an attack. 

Regular activity to maintain health is an important part of the management of Chester porphryia. 

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Hemin (Panhematin)

• Dosing, Interactions, etc.

Clinical Context:  Limits rate of hepatic and/or marrow porphyria/heme biosynthesis, possibly by inhibiting the enzyme aminolevulinic acid synthetase. Indicated for amelioration of recurrent attacks of acute intermittent porphyria temporally related to the menstrual cycle in susceptible women.

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Givosiran (Givlaari)

• Dosing, Interactions, etc.

Clinical Context:  Double-stranded small-interfering RNA that causes degradation of aminolevulinate synthase 1 (ALAS1) mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of acute hepatic porphyria.

Indicated for acute hepatic porphyria.

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