Diagnosis and management of porphyria

British Medical Journal, June 17, 2000 by Helen Thadani, Allan Deacon, Timothy Peters

Summary points

The porphyrias form a group of inherited disorders of haem biosynthesis of which there are seven main

Porphyrias can be classified into acute (neuropsychiatric), cutaneous, and mixed forms

Acute forms can be life threatening, but attacks can be aborted by early administration of haem arginate

The acute porphyrias are often misdiagnosed; most commonly they present as acute abdominal pain or as neurological or atypical psychiatric symptoms

Patients with porphyria should be referred to specialist centres and be advised to avoid precipitating factors, such as certain drugs

When a patient is diagnosed with an acute porphyria the whole family needs to be screened

Although porphyria is a relatively uncommon condition, it should be considered in patients presenting with an atypical medical, psychiatric, or surgical history. Acute attacks are associated with a substantial morbidity and mortality; there is a need for rapid and accurate diagnosis of the neuropsychiatric porphyrias, particularly because haem arginate can induce a definite remission if given early in an attack. Additionally, porphyrias may present with skin lesions or photosensitivity.

What are the porphyrias?

The porphyrias form a heterogeneous group of inherited disorders of haem biosynthesis, and they are often missed or wrongly diagnosed. A partial deficiency of one of the seven enzymes in the pathway causes characteristic clinical and biochemical features. These disorders are due to a specific alteration in the pattern of accumulation of porphyrin and porphyrin precursors (table). Each type of porphyria is defined by a unique pattern of accumulation and excretion of haem precursors, as well as a reduction in the relevant enzyme activity. Correct interpretation of the appropriate biochemical investigations is essential for accurately diagnosing and managing the porphyrias, as clinical features alone are not sufficiently specific either to confirm a diagnosis or to distinguish between the various forms.

Summary of diagnosis patterns of overproduction of haem precursors in different porphyrias

                                      Urine concentration

                                      Porphobilinogen and
Type of porphyria                     aminolaevulinic acid

Plumboporphyria(*)                    Aminolaevulinic acid

Acute intermittent porphyria          Porphobilinogen >
                                      aminolaevulinic acid

Congenital erythropoietic porphyria   Not increased

Porphyria cutanea tarda               Not increased

Hereditary coproporphyria             Porphobilinogen >
                                      aminolaevulinic acid

Variegate porphyria                   Porphobilinogen >
                                      aminolaevulinic acid

Erythropoietic protoporphyria         Not increased

                                      Urine concentration

Type of porphyria                     Porphyrins

Plumboporphyria(*)                    Coproporphyrinogen III

Acute intermittent porphyria          Porphyrin mainly from
                                      porphobilinogen

Congenital erythropoietic porphyria   Uroporphyrinogen I >
                                      coproporphyrinogen I

Porphyria cutanea tarda               Uroporphyrinogen >
                                      heptacarboxylate

Hereditary coproporphyria             Coproporphyrinogen III
                                      (porphyrin mainly from
                                      porphobilinogen)

Variegate porphyria                   Coproporphyrinogen III
                                      (porphyrin mainly from
                                      porphobilinogen)

Erythropoietic protoporphyria         Not increased

Type of porphyria                     Porphyrins in faeces

Plumboporphyria(*)                    Not increased

Acute intermittent porphyria          Normal, occasionally slight
                                      increase (coproporphyrinogen,
                                      protoporphyrin)

Congenital erythropoietic porphyria   Coproporphyrinogen I

Porphyria cutanea tarda               Isocoproporphyrinogen,
                                      heptacarboxylate

Hereditary coproporphyria             Coproporphyrinogen III

Variegate porphyria                   Protoporphyrin IX >
                                      coproporphyrinogen III and
                                      porphyrin X

Erythropoietic protoporphyria         Protoporphyrin increased or
                                      decreased

Type of porphyria                     Porphyrins in erythrocytes

Plumboporphyria(*)                    Zinc protoporphyrin

Acute intermittent porphyria          Not increased

Congenital erythropoietic porphyria   Zinc protoporphyrin,
                                      coproporphyrinogen,
                                      uroporphyrinogen

Porphyria cutanea tarda               Not increased

Hereditary coproporphyria             Not increased

Variegate porphyria                   Not increased

Erythropoietic protoporphyria         Protoporphyrin

(*) Lead poisoning produces an identical overproduction pattern.

There are seven main types of porphyria (fig 1), which are broadly classified according to clinical features into neuropsychiatric, dermatological, and mixed forms. Acute intermittent porphyria and plumboporphyria are predominantly neuropsychiatric; congenital erythropoietic porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria have predominantly cutaneous manifestations; and hereditary coproporphyria and variegate porphyria are classified as mixed as they may have both cutaneous and neuropsychiatric features. The prevalence of porphyria varies widely from country to country and also depends on the type of porphyria. Overall prevalence of overt cases in the United Kingdom is about 1 in 25 000 population for porphyria cutanea tarda and less than 1 in one million for congenital erythropoietic porphyria.[1] Plumboporphyria has not been reported in Britain.

[Figure 1 ILLUSTRATION OMITTED]

Methods

We based this article on literature reviews, including a Medline search (1966-98), and on the many years' experience of our department in the management of the porphyrias. King's College Hospital is one of the two recently established supraregional assay service centres for laboratory diagnosis and for the provision of clinical advice on the management of porphyria.

General clinical aspects

Patients with porphyria present in three different ways--with cutaneous lesions, acute attacks (see below for features), or both. Clinically identical acute attacks can occur in acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and plumboporphyria.[2] Skin lesions accompany the acute attack in about half of patients with variegate porphyria and in about a third of patients with hereditary coproporphyria[2]; skin lesions may be the sole presentation in these porphyrias.

Acute attacks

Acute intermittent porphyria is the commonest of the acute porphyrias. The clinical features of an acute attack vary greatly. The most common symptom is severe abdominal pain, which may be accompanied by neurological and psychiatric symptoms (fig 2).[3] Muscular weakness, particularly a proximal myopathy affecting the arms, is common. Muscular weakness can, however, progress to quadraparesis and respiratory paralysis and arrest, which may resemble the Guillain-Barre syndrome. Mild sensory changes often accompany the predominantly motor neuropathy--often in a "bathing trunk" distribution.[4]