Osteosarcoma and Propionic Acidemia: Chronicle of a Crisis Foretold

Background: Inborn errors of metabolism (IEMs) associated with cancer represent a unique clinical challenge, as there is an increased risk of toxicity resulting from chemotherapy interaction.

Case Study: A 4-year-old female preschooler, born at term from a consanguineous union in first grade, without perinatal noxa, presented with emesis and subsequent encephalopathy associated with metabolic acidosis. IEM was suspected, with subsequent confirmation of propionic acidemia (PPA). The patient was under conventional nutritional treatment with good metabolic control for around 5 years. At 9 years old, osteoblastic osteosarcoma was diagnosed with involvement of the physis on the medial side of the left femur without metastatic disease type IIA.

Results: The patient received neoadjuvant chemotherapy with doxorubicin, phosphamide and cisplatin presenting complications including cardiogenic shock secondary to cardiotoxicity from anthracyclines and metabolic crisis associated with her IEM that only required nutritional management adjustment.

Conclusion: There is limited anecdotal evidence of oncogenesis in intoxication-type IEMs like organic acidurias. To the best of our knowledge, this is the first report of cancer in a patient with PPA. Although for some organic acidurias, the metabolic defect seems to trigger tumorigenesis, their relationship with classical organic acidurias is uncertain. However, the accumulation of multiple toxic metabolites that favour mitochondrial dysfunction, alteration of the tricarboxylic acid cycle, oxidative stress, and potentially oncometabolites might influence tumorigenesis. Furthermore, the catabolic state associated with chemotherapy would worsen or potentially destabilise organic acidurias. Thus, socialising individual experiences might contribute to developing strategies to prevent drug toxicity and increase the benefits of treatment.