Porphyrias

Porphyrias (synonyms: porphyria; erythropoietic porphyria; congenital erythropoietic porphyria; porphyria cutanea tarda; hepatoerythropoietic porphyria; acute intermittent porphyria; porphyria variegata; hereditary coproporphyria; Doss porphyria; δ-ALS-deficiency porphyria; ALAD-deficiency porphyria; ICD-10-GM E80.-: Disorders of porphyrin and bilirubin metabolism) represent a group of rare metabolic disorders in which the formation of the red blood pigment heme is impaired due to an enzyme defect. The enzyme defect leads to an accumulation of intermediate products of heme biosynthesis, which are deposited in the organs. Which organs are impaired in their function depends on which enzyme is affected by the defect. According to the cause, a distinction is made between primary (genetically determined) and secondary (acquired) porphyrias:

Primary porphyrias

  • Acute intermittent porphyria (AIP) (most common acute form) – ICD-10-GM E80.2: Other porphyria; autosomal dominant.
  • Porphyria variegata (PV) – ICD-10-GM E80.2: Other porphyria; autosomal dominant.
  • Hereditary coproporphyria (HCP) – ICD-10-GM E80.2: Other porphyria; autosomal dominant.
  • Doss porphyria (δ-ALA-deficiency porphyria/ALAD-deficiency porphyria) – ICD-10-GM E80.2: Other porphyria; autosomal recessive.
  • Porphyria cutanea tarda (PCT) – ICD-10-GM E80.1; most common form; autosomal dominant or acquired
    • Subform: hepatoerythropoietic porphyria (HEP) – ICD-10-GM E80.2: other porphyria; autosomal recessive, severe form of progression
  • Congenital erythropoietic porphyria (CEP) (synonym: Günther’s disease) – ICD-10-GM E80.0: Hereditary erythropoietic porphyria; autosomal recessive.
  • Erythropoietic porphyria (EPP) – ICD-10-GM E80.0: Hereditary erythropoietic porphyria; autosomal dominant.

Secondary porphyrias

  • Coproporphyrias (acquired)
  • Protoporphyrinemias (acquired)

The hereditary (primary) porphyrias can skip several generations. The porphyrias can be divided into the following two groups depending on where the porphyrins mainly accumulate:

  • Hepatic porphyrias (common) – the porphyrins accumulate mainly in the liver.
    • Porphyria cutanea tarda (PCT).
      • Subtype: hepatoerythropoietic porphyria (HEP).
    • Acute hepatic porphyria (AHP): upregulation of δ-aminolevulinic acid-1 synthase (ALAS1) leading to accumulation of δ-aminolevulinic acid (ALA) and porphobilinogen.
    • Acute intermittent porphyria (AIP).
    • Porphyria variegata (PV)
    • Hereditary coproporphyria (HCP)
    • Doss porphyria (δ-ALA-deficiency porphyria/ALAD-deficiency porphyria).
  • Erythropoietic porphyrias (rare) – porphyrins accumulate mainly in the bone marrow
    • Erythropoietic porphyria (EPP).
    • Congenital erythropoietic porphyria (CEP) (synonym: Günther’s disease).

For more on the classification of porphyrias, see “Classification”. Sex ratioAcute intermittent porphyria: males to females is 1: 2-3.Porphyria cutanea tarda: males to females is 2: 1.Frequency peakAcute intermittent porphyria occurs predominantly between the 2nd and 4th decade of life.Porphyria cutanea tarda occurs predominantly from the 4th decade of life.Erythropoietic porphyria occurs in childhood. The other forms of porphyria are very rare and thus not worth mentioning in this context. The prevalence (frequency of disease) of porphyria cutanea tarda is 1: 2,000 to 1: 5,000, that of acute intermittent porphyria is 5.9 cases per 1,000,000 and that of congenital erythropoietic porphyria is 1: 2,000,000.The incidence (frequency of new cases) for acute intermittent porphyria is approximately 0.13 cases per 1,000,000 population per year (in Europe). Course and prognosis: The symptoms that develop depend on which enzyme is affected by the disorder. The heme precursors or porphyrins accumulate especially in the skin and liver. In the acute forms of porphyria, abdominal pain (abdominal pain) and neurologic symptoms are most common. In the non-acute forms, the skin is primarily affected. A typical feature of porphyrias is their relapsing course, in which asymptomatic phases alternate with acute episodes (attacks, seizures) that can last one to two weeks. The severity of porphyria varies.In the acute forms, sufferers usually recover well from an episode. Most sufferers can lead a relatively normal life. There are also carriers of the gene who suffer few attacks to none in their lives. The cutaneous forms may be associated with liver damage, so regular medical check-ups are required.Severe recurrent (recurring) attacks increase the risk of kidney damage and permanent neurological impairment.There is no causal therapy for the genetic porphyrias. Often, porphyria is not recognized as such due to the complex nonspecific symptoms, so patients with neurological or psychiatric symptoms are ultimately classified as mentally ill. If porphyria is suspected, the affected person should be referred to a porphyria center of excellence (www.epp-deutschland.de).