ISSN 2398-2993      

Bovine congenital erythropoietic protoporphyria

obovis
Contributor(s):

Mo Kemp

Eoin Ryan

Synonym(s): BCEP, Porphria, Congenital protoporphyria, Bovine congenital erythrocytic protoporphyria


Introduction

This article discusses Bovine Congenital Erythropoietic Protoporphyria. At the time of publication, there is a lack of substantive literature on this topic and there appears to be some confusion, between publications, as to whether there are two separate disease entities – one type affecting Limousin and Blonde d’Aquitaine cattle and the other affecting Holstein cattle. Both disease presentations are reported to be clinically identical and the management and prognosis of each is also identical, although the pathogenesis is subtly different. Therefore, the Editors have opted to present this as one condition but draw the reader’s attention to the possible differences that may be considered. If and when new evidence comes to light, then this article will be reviewed and updated.
  • Bovine congenital erythropoietic protoporphyria presents as photosensitization caused by elevated concentrations of porphyrin precursors and porphyrins.
  • Cause: in cattle it is an autosomal recessive trait with heterozygous animals appearing normal but homozygous recessive animals are affected from birth.
  • Signs: with increasing exposure to sunlight, affected animals develop classic signs of photosensitization and photophobia. Some Limousin and Blonde d’Aquitaine animals have been reported to suffer neurologic signs and seizures.
  • Diagnosis: see below.
  • Treatment: symptomatic treatment. Affected animals should be kept indoors and out of direct sunlight.
  • Prognosis: guarded.

Pathogenesis

Etiology

  • In human medicine the inherited porphyria’s are a diverse group of errors of heme synthesis, each caused by the deficient activity of a specific enzyme in the heme pathway. Porphyria’s are classified as either hepatic or erythropoietic, according to whether the excess production of porphyrin precursors and porphyrins occurs primarily in the liver or in the red cells and their precursors. As far as the Authors and Editors are aware, only erythropoietic porphyria’s have been described in cattle.
  • The mechanism is believed to be as follows:
    • In healthy animals, the enzyme ferrochelatase converts protoporphyrin to heme by inserting ferrous iron. This enzyme is found in the mitochondria and is one of eight enzymes involved in the heme pathway.
    • In affected homozygous animals, the ferrochelatase gene is faulty and as such this stage of the heme synthesis pathway does not occur and protoporphyrin therefore accumulates in blood and tissues.
  • Another mechanism has also been described:
    • BCEP has been postulated to occur due to a rare autosomal recessive trait that results in a decrease of uroporphyrinogen III synthase (URO-synthase) activity.
    • URO-synthase is the fourth enzyme in the heme biosynthesis pathway and it normally converts hydroxymethylbilane to uroporphyrinogen III. It is found in the cytoplasm of the cell.
    • With decreased URO-synthase there is a buildup of hydroxymethylbilane in red blood cells which convert to uroporphyrinogen I.
  • Regardless of the exact mechanism, the result is the same:
    • Porphyrinogen/protoporphyrin accumulate in large amounts and can become pathological.
    • Accumulations of Porphyrinogen/protoporphyrin in the bone marrow can lead to cell damage and hemolysis.
    • Porphyrinogen/protoporphyrin are released into the circulation and can be deposited in the skin, bone and other tissues. In the skin the porphyrins are photocatalytic and cytotoxic leading to cutaneous photosensitivity.
    • Exposure of the skin to sunlight leads to excitation of isomers, formation of oxygen radicals and subsequent tissue and vessel damage.
  • Why do seizures occur?
    • Seizures were postulated to occur due to accumulation of δ-Aminolevulinic acid, an endogenous non-proteinogenic amino acid, which is the first compound in the porphyrin synthesis pathway. The δ-Aminolevulinic acid competitively inhibits γ-amino-butyric acid (GABA) a primary inhibitory neurotransmitter of the central nervous system.
    • However, it is now believed that although this molecule may be responsible for neuropathic pain observed in affected individuals, seizures are more likely attributed to metabolic imbalances such as hyponatremia.

Timecourse

  • The condition is present from birth, but signs often only detected after exposure to sunlight or poor growth rate is detected.

Epidemiology

  • The recessive genetic character is widely distributed but the clinical condition is comparatively rare.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • McAloon C G, Doherty M L, O’Neill H, Badminton M & Ryan E G (2015) Bovine congenital erythropoieticprotoporphyria in a crossbred limousin heifer in Ireland. Ir Vet J 68 (1), 15 PubMed.
  • Dsnick R J & Astrin K H (2002) Congenital erythropoietic porphyria: advances in pathogenesis and treatment. Br J Haematol 117 (4), 779-795 PubMed.
  • Armstrong S, Jonsson N & Barrett D (2002) Bovine congenital erythrocyticprotoporphyria in a Limousin calf bred in the UK. Vet Rec 150 (19), 608–610 PubMed.
  • Buchanan M & Crawshaw W M (1995) Bovine congenital erythropoieticprotoporphyria in a pedigree Limousin heifer. Vet Rec 136 (25), 640 PubMed.
  • Lauvergne J J & Pinault L (1991) Protoporphyrie héréditaire en race bovine Limousine française, premiers résultats. Genet Sel Evol 23 (14), 339–343 NCBI
  • Schelcher F, Delverdier M, Bezille P, Cabanie P, Espinasse J (1991) Observation onbovine congenital erythrocytic protoporphyria in the Blonde d’Aquitaine breed. Vet Rec 129 (18) 403–407 PubMed.
  • Rhode E A & Cornelius C E (1958) Congenital porphyria (pink tooth) in Holstein-fresian calves in California. JAVMA 132 (3), 112-116 PubMed.

Other sources of information

  • Aiello S E & Moses M A (2016) Metabolic Disorders. In: The Merck Veterinary Manual. 11th edn. Wiley, USA. pp 986-987.
  • Carlson G P (1996) Erythropoietic Porphyria Chapter: Diseases of the Hematopoietic and Hemolymphatic Systems. In: Large Animal Internal Medicine. Ed: Smith B P. pp 1231.
  • Rebhun W C (1995) Skin Diseases. In: Diseases of Dairy Cattle. pp 239.

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