Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital erythropoietic porphyria (CEP) is a recessive autosomal disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. The severity of the disease, the lack of specific treatment except for allogeneic bone marrow transplantation, and the knowledge of the molecular lesions are strong arguments for gene therapy. An animal model of CEP has been designed to evaluate the feasibility of retroviral gene transfer in hematopoietic stem cells. We have previously demonstrated that the knockout of the Uros gene is lethal in mice (Uros(del) model). This work describes the achievement of a knock-in model, which reproduces a mutation of the UROS gene responsible for a severe UROS deficiency in humans (P248Q missense mutant). Homozygous mice display erythrodontia, moderate photosensitivity, hepatosplenomegaly, and hemolytic anemia. Uroporphyrin (99% type I isomer) accumulates in urine. Total porphyrins are increased in erythrocytes and feces, while Uros enzymatic activity is below 1% of the normal level in the different tissues analyzed. These pathological findings closely mimic the CEP disease in humans and demonstrate that the Uros(mut248) mouse represents a suitable model of the human disease for pathophysiological, pharmaceutical, and therapeutic purposes.
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PMID:A knock-in mouse model of congenital erythropoietic porphyria. 1631 73

Congenital erythropoietic porphyria is a rare disorder of heme biosynthesis, resulting from decreased enzymatic activity of uroporphyrinogen III synthase. Clinical manifestations are heterogenous, of variable severity, and with occasional phenotypic-genotypic correlation. A 14-month-old boy developed fever, extensive dermatitis, and reddish colored urine. Anemia, erythrodontia, hepatosplenomegaly, and massive urinary elimination of predominantly type I porphyrins was suggestive of congenital erythropoietic porphyria. Although hemolysis remained mild and compensated, facial and digital mutilation developed indicative of moderate clinical phenotype. Mutational analysis revealed compound heterozygosity of mutant alleles, including a novel mutation (p.Pro190Leu). The child received supportive management and underwent facial reconstruction successfully.
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PMID:Report of a novel Indian case of congenital erythropoietic porphyria and overview of therapeutic options. 2361 87