Image Based Question-69881

A child presented with Severe photosensitivity,Teeth abnormalities as shown in the image and splenomegaly.Which enzyme defect in the metabolism of heme might be responsible for this condition?

A. Uroporphyrinogen 1 synthase.

B. Uroporphyrinogen Carboxylase.

C. Uroporphyrinogen III cosynthase.

D. Ferrochetalase.

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Correct Answer » C Explanation

Ans:C. Uroporphyrinogen III cosynthase.

• The image shows A: Yellowish coloration of the teeth of a child with congenital erythropoietic porphyria. B :Red fluorescence (erythrodontia) can be readily observed under Wood light.

CONGENITAL ERYTHROPOIETIC PORPHYRIA

• Biochemical Defect :An autosomal recessive disorder characterized by markedly deficient activity of URO III cosynthetase.

Pathophysiology:

• URO III cosynthetase is involved in the conversion of preuroporphyrinogen to uroporphyrinogen III during the biosynthesis of heme.

• When this enzyme is deficient, uroporphyrin I and coproporphyrin I (isomers/derivatives of preuroporphyrinogen) accumulate in the bone marrow, erythrocytes, teeth, plasma, and urine.

• Porphyrin deposition in the teeth leads to discoloration, whereas increased levels of erythrocyte porphyrins lead to increased hemolysis and splenomegaly.

• Porphyrins can also damage the bone marrow, leading to an increased susceptibility to infections.

• Porphyrin deposition in the skin results in the formation of oxygen-free radicals, which can then damage cells and lead to photosensitivity.

Clinical Manifestations :

• Severe cutaneous photosensitivity in early infancy with the appearance of friable bullae and vesicles. Other skin symptoms include skin thickening, focal pigmentation abnormalities, and facial and extremity hypertrichosis. Patients also suffer from disfigurement of face and hands, reddish-brown teeth, and splenomegaly.

Lab findings: Elevated levels of uroporphyrin I and coproporphyrin I in the urine.

Treatment : Blood transfusion to suppress erythropoiesis; splenectomy to reduce hemolysis; β-carotene supplementation (free radical scavenger); possible bone marrow transplantation in severe cases.