2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Congenital Erythropoietic Porphyria: Variable Age of Onset of Porphyrinuria, an Indicator of Disease Severity and Correlation With Genotype

Congenital Erythropoietic Porphyria: Variable Age of Onset of Porphyrinuria, an Indicator of Disease Severity and Correlation With Genotype

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Pdf Summary

Congenital erythropoietic porphyria (CEP) is a rare genetic disorder caused by mutations in the UROS gene, leading to a deficiency in the enzyme UROS and the accumulation of toxic porphyrins. The severity of the disease varies, with symptoms appearing from infancy to adulthood and including porphyrinuria, photosensitivity, and anemia. Treatment involves maintaining a hematocrit level above 35% and bone marrow transplantation has been curative for some patients.<br /><br />A literature review of CEP patients from 2000 to 2023 found 75 individuals with available clinical information. They were divided into five groups based on age at presentation or diagnosis. The presence of red urine or amniotic fluid, skin findings, anemia, transfusion dependence, and UROS genotype were analyzed.<br /><br />The results showed that porphyrinuria is not always present at birth in CEP patients. Younger age at presentation or diagnosis was correlated with a higher incidence of anemia, transfusion dependence, and a specific UROS gene variant (p.C73R). Patients with this variant had more severe disease due to almost absent residual enzyme activity.<br /><br />On the other hand, patients with later onset of porphyrinuria tended to have less severe disease, with a lower incidence of anemia and no transfusion dependency. Porphyrinuria can be used as an indicator for management decisions, especially in patients with a combination of the p.C73R variant and another UROS variant.<br /><br />Overall, this study highlights the variable age of onset of porphyrinuria in CEP patients, which is indicative of disease severity. Understanding the correlation between age of onset and genotype can aid in predicting disease progression and guiding treatment decisions for individuals with CEP.

Asset Subtitle

Presenting Author - Angelika L. Erwin, MD, PhD; Co-Author - Manoj K. Agarwala, MD; Co-Author - Hetanshi Naik, PhD, MS, CGC; Co-Author - Allison Schreiber, MS; Co-Author - Manisha Balwani; Co-Author - Robert J. Desnick, MD, PhD;

Meta Tag

Genotype-Phenotype Correlations

Metabolic Disorder

Phenotypic delineation of disorders

Co-Author Manoj K. Agarwala, MD

Co-Author Hetanshi Naik, PhD, MS, CGC

Co-Author Allison Schreiber, MS

Co-Author Manisha Balwani

Co-Author Robert J. Desnick, MD, PhD

Presenting Author Angelika L. Erwin, MD, PhD

Keywords

Congenital erythropoietic porphyria

CEP

genetic disorder

UROS gene

enzyme deficiency

toxic porphyrins

porphyrinuria

photosensitivity

anemia

bone marrow transplantation