Is there a risk of fungal infection in patients with propionic acidemia?

Risk of Fungal Infections in Patients with Propionic Acidemia

Patients with propionic acidemia are at increased risk for fungal infections due to their underlying immune dysfunction, with approximately 80% experiencing infections, many caused by unusual microorganisms including fungi.1

Immune Dysfunction in Propionic Acidemia

Propionic acidemia (PA) causes immune system impairment through several mechanisms:

• Direct immunosuppressive effect: Propionic acid accumulation inhibits lymphocyte proliferation and function, particularly affecting responses to mitogens like phytohaemagglutinin, concanavalin A, and pokeweed mitogen 2
• Global immune impact: The disease affects both T and B lymphocytes as well as bone marrow cells 1
• Metabolic derangements: Acute metabolic decompensation episodes further compromise immune function

Fungal Infection Risk Profile

The risk of fungal infections in PA patients is characterized by:

• High infection frequency: 80% of PA patients experience infections, with many caused by unusual organisms 1
• Severe phenotype: Particularly notable in populations with consanguinity 1
• Persistence despite treatment: Infections occur despite aggressive dietary management, carnitine supplementation, and metronidazole during acute episodes 1

Common Fungal Pathogens

Based on evidence from immunocompromised populations, PA patients may be susceptible to:

• Candida species: Common in immunocompromised patients, causing both superficial and invasive infections 3
• Aspergillus species: Account for 78% of fungal infections in primary immunodeficiency patients 4
• Pneumocystis jirovecii: Causes life-threatening pneumonia in immunocompromised hosts 3
• Rare fungi: Including Fusarium, Mucormycosis, and other opportunistic fungi 4

Monitoring and Prevention Strategies

For PA patients, implement the following monitoring and prevention strategies:

1. Regular surveillance: Monitor for signs of infection during routine health supervision visits
2. Prompt evaluation: Investigate any fever or signs of infection immediately, as PA patients may have atypical presentations
3. Fungal biomarkers: Consider galactomannan testing if aspergillosis is suspected 3
4. Environmental precautions:
   • Avoid high-risk exposures (construction areas, gardening without protection)
   • Avoid foods with high fungal content (spices, non-pasteurized beer, blue cheeses) 3
   • Maintain good hand hygiene 3

Treatment Considerations

When fungal infection is suspected or confirmed:

1. Early intervention: Initiate appropriate antifungal therapy promptly
2. Consultation: Involve infectious disease specialists in management
3. Source control: Address any removable sources of infection (e.g., central venous catheters) if present
4. Antifungal selection: Choose based on suspected pathogen and local epidemiology
5. Metabolic stabilization: Simultaneously manage metabolic parameters to prevent decompensation

Special Considerations

• During metabolic crises: Heightened vigilance for opportunistic infections is necessary
• Hospitalization: Consider protective isolation with HEPA filtration for severely immunocompromised PA patients
• Prophylaxis: Consider antifungal prophylaxis for high-risk patients (e.g., those with recurrent infections or severe metabolic instability)

The management of PA patients requires close attention to infectious complications, particularly fungal infections, which can significantly impact morbidity and mortality in this vulnerable population.