Key role of Levitt’s carbon monoxide breath test in revealing coexistent Gilbert syndrome and erythropoietic protoporphyria: A case report

BACKGROUND: It is challenging to diagnose isolated hyperbilirubinemia with rare and complex etiologies under the constraints of traditional testing conditions. Herein, we present a rare case of coexisting Gilbert syndrome (GS) and erythropoietic protoporphyria (EPP), which has not been previously documented. CASE SUMMARY: We present a rare case of coexisting GS and EPP in a 23-year-old Chinese male with a long history of jaundice and recently found splenomegaly. Serial non-specific hemolysis screening tests yielded inconsistent results, and investigations for common hemolytic etiologies were negative. However, Levitt's carbon monoxide breath test, which measures erythrocyte lifespan (the gold-standard marker of hemolysis), demonstrated significant hemolysis, revealing a markedly shortened erythrocyte lifespan of 11 days (normal average 120 days). Genetic testing subsequently confirmed EPP with a homozygous ferrochelatase gene mutation and GS with a heterozygous uridine diphosphate glucuronosyl transferase 1A1 gene mutation. CONCLUSION: The rapid, non-invasive Levitt's carbon monoxide breath test resolved the diagnostic challenge posed by a rare and complex cause of hyperbilirubinemia.