Hereditary Coproporphyria

Hereditary coproporphyria is a form of acute hepatic porphyria (see this term) characterized by the occurrence of neuro-visceral attacks and, more rarely, by the presence of cutaneous lesions.

Epidemiology

The prevalence in Europe is estimated at about 1/1,000,000.

Clinical description

The disease manifests after puberty and preferentially affects women. Patients suffer neuro-visceral attacks, which can persist for several weeks and manifest as intense abdominal pain (in 85-95% of cases), and neurological and psychological symptoms. The abdominal pain is often associated with lumbago irradiating to the thighs, and with nausea, vomiting and constipation. Psychological symptoms are variable: irritability, emotionality, depression, considerable anxiety and, more rarely, auditory and visual hallucinations, disorientation, mental confusion. Neurological manifestations can affect the central nervous system as much as the peripheral nervous system (myalgia, paresis, ascending flaccid paralysis of the limbs, or convulsions) and can lead to severe complications such as motor paralysis. Tachycardia and hyponatremia are common during attacks. In cases with cardiac arrhythmia and respiratory paralysis (rare), attacks can be fatal. The attacks are most commonly triggered by exogenous factors (porphyrinogenic drugs, alcohol, infections, a hypo-calorific diet, stress), and/or endogenous factors (hormonal, linked to menstrual cycle). In 30% of cases patients present with cutaneous lesions as a result of photosensitivity. These lesions predominate in areas exposed to the sun (hands, face). They manifest as bullae that cause differing degrees of pain and that leave scars that are often hyperpigmented.

Etiology

Hereditary coproporphyria is caused by a deficiency of coproporphyrinogen oxidase (CPO, the sixth enzyme in the heme biosynthesis pathway) that leads to an accumulation of porphyrins and their precursors in the liver (delta-aminolevulinic acid, ALA and porphobilinogen, PBG). The enzyme deficiency is caused by mutationsof the CPOX gene coding for CPO (3q12). Transmission is autosomal dominant.

Diagnostic methods

The observation of reddish or dark brown urine evokes the diagnosis of the disease. Diagnosis is based on evidence of elevated concentrations of ALA, PBG and of uroporphyrins and coproporphyrins in the urine.

Differential diagnosis

Differential diagnoses include acute intermittent porphyria and, especially, variegate porphyria (see these terms).

Genetic counseling

Genetic counseling should be offered to patients and families to identify individuals susceptible to developing or transmitting the disease.

Management and treatment

When an acute attack is confirmed, urgent treatment with an injection of human hemin and/or perfusion of carbohydrates is required. Management includes the suppression of triggering factors, relief from pain (opiates), vomiting and anxiety, and the prevention of attacks (by avoiding triggering factors, particularly drugs).

Prognosis

With early diagnosis and management, attacks from porphyria are rarely fatal. Acute attacks are more rare than in cases of acute intermittent porphryia and, if the triggering factors are eliminated, the disease is rarely progressive.