Congenital Erythropoietic Porphyria

What is porphyria?

Porphyrias are metabolic disorders that occur due to altered enzyme activity in heme biosynthesis pathways.

What is heme biosynthesis?

The major tissues for heme biosynthesis include bone marrow and liver. Heme is the essential molecule that is required for :

• Heme is required as the component of hemoglobin
• It is required as the component of myoglobin
• It is required as the component of electron transport chain (ETC) enzymes
• Heme is also involved in cytochrome p450

According to Nelson, around 85% of heme synthesis majorly occurs in the bone marrow (erythroid precursors). Around 14% of all heme synthesis tends to occur in the liver and 1% of heme synthesis, which is in negligible form, is found in any other tissues.

The Cycle of Heme synthesis

Also read: Pediatric Hematology Important Topics 

What is Congenital Erythropoietic Porphyria (CEP)?

• Synonym: Gunther's disease.
• Enzyme deficiency: Uroporphyrinogen III synthase.
• Autosomal recessive inheritance.
• The UROS gene on the 10q gene is responsible for congenital erythropoietic porphyria.
• The most common mutation, C73R, occurs in 33% of patients. Moderate to severe type of presentation
• Due to a deficiency of Uroporphyrinogen 3 synthase, the hydroxymethylbilane will not get converted to Uroporphyrinogen 3
• Hydroxymethylbilane will be accumulated, which will convert into uroporphyrinogen 1 and further to uroporphyrin 1.
• Uroporphyrinogen 1 can be converted into coproporphyrinogen I Coproporphyrinogen 1 and further to coproporphyrin 1.

Pathogenesis of Congenital Erythropoietic Porphyria

It occurs due to an increase in tissue accumulation of porphyrins.

• Porphyrins activate photosensitive mechanisms
• This leads to RBC damage and further hemolysis.
• RBC damage can also be caused by increased porphyrins in the absence of a photosensitive mechanism.

Ineffective erythropoiesis will lead to:

• Expansion of medullary spaces
• Weakening the bones
• Facial dysmorphism and bone disease.

Clinical features of Congenital Erythropoietic Porphyria

• Non-immune fetal hydrops
  • In severe forms, the patient may have intrauterine hemolysis.
• Pathological Jaundice in Neonates
  • Paradoxically, photography worsens the condition.
• Reddish pink urine and meconium
  • There will be discoloration of diapers.
  • The color will be enhanced when UV lamps are used.
• Blisters on a sun-exposed area
  • It can be recurrent, leading to pigmentary changes, scarring, and hypertrichosis.
• Erythrodontia
  • Pink teeth will be observed under UV light due to the accumulation of these pigments.
• Facial deformities, infections, and corneal damage.
• Splenomegaly
  • Splenomegaly will lead to decreased hemoglobin, platelet, and neutrophil counts.
  • Transfusion: Dependence in severe forms
• Long-standing cases
  • Liver disease due to chronic transfusions.

Also read: Important MCQ’s in Hematology for NEET SS Pediatrics

Reddish pink stain in diapers 

Pink teeth under UV light 

Investigations of Congenital Erythropoietic Porphyria 

• CEP is the condition where the highest level of circulating porphyrins is found. In CEP in urine, coproporphyrin 1 and Uroporphyrin 1 are significantly present. 50-100mg/day. Stool excretion and RBC levels of Coproporphyrin1 and Uroporphyrin1 are also high. Definitive diagnosis
  • UROS activity estimation can be done.
  • UROS mutation can be done.
• Prenatal diagnosis in Nonimmune fetal hydrops: UROS activity in culture cells from amniotic fluid.

Treatment of Congenital Erythropoietic Porphyria 

• Protection from sunlight exposure. Sunscreen used should have a sun protection factor of more than 30.
• Skin trauma should be minimized.
• Prompt treatment of any cutaneous infection.
• Blood transfusion.
• Concurrent deferoxamine to reduce iron overload
• Hydroxyurea to suppress erythropoiesis may provide additional benefits.
• Splenectomy is useful in a few cases.
• Doubtful role IV haemin, oral charcoal (Increase stool excretion of porphyrins)
• Definitive therapy - Stem cell transplantation.

Also read: Important Topics for Pediatric Oncology Preparation

Important Points to Remember 

• Adult onset CEP or late-onset cases are likely associated with myeloproliferative disorders and expansion of a clone of cells carrying a UROS mutation. In most CEP patients
  • No neurological symptoms are there.
  • No drug-induced worsening is seen.
• Heme synthesis in bone marrow is usually preserved. Hemolysis and ineffective erythropoiesis are responsible for the manifestations that are seen.

Drugs unsafe in Porphyria

• Antiepileptics: Barbiturates, Phenytoin, Carbamazepine, Valproate, Clonazepam : Clonazepam is relatively safe
• Sulfonamides, Griseofulvin, Fluconazole
• Alcohol
• Ergot, Metoclopramide
• Ketoconazole
• Spironolactone
• OCP'S/Progesterone, Danazol
• Diclofenac (Paracetamol is safe).
• ACEIs, CCBs.
• Ketamine
• Antitubercular Drugs: Rifampicin, Pyrazinamide

Hope you found this blog helpful for your NEET SS Pediatrics Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs. 

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