Bilateral Renal Fungal Bezoars and Perinephric Abscess in an Infant With Arthrogryposis-Renal Dysfunction-Cholestasis...

Area of Science:

• Pathology
• Genetics
• Immunology

Background:

• Arthrogryposis-Renal dysfunction-Cholestasis (ARC) syndrome is linked to VPS33B mutations, impacting phagolysosome fusion and causing immune susceptibility.
• Autopsy data on ARC syndrome is scarce, limiting detailed pathological understanding.
• This study presents the first autopsy case of ARC syndrome in a 2-month-old infant.

Purpose of the Study:

• To describe the detailed pathology of the first autopsy case of ARC syndrome.
• To investigate the pathological basis of opportunistic infections and organ-specific manifestations in ARC syndrome.
• To elucidate the mechanisms underlying neurogenic amyotrophy in ARC syndrome.

Main Methods:

• Comprehensive autopsy and histopathological examination of a 2-month-old male infant with ARC syndrome.
• Detailed analysis of renal, hepatic, pulmonary, and neurological tissues.
• Correlation of pathological findings with genetic factors (VPS33B) and clinical presentation.

Main Results:

• The infant died from recurrent sepsis and multiorgan failure, with autopsy revealing invasive renal candidiasis, including pyelonephritis, fungal bezoars, and perinephric abscess.
• Severe chronic liver changes were observed, characterized by cholestasis, multinucleated hepatocytes, fibrosis, and bile duct proliferation.
• Neuropathological examination was unremarkable, suggesting amyotrophy is not due to defects in cell survival-related autophagy.

Conclusions:

• ARC syndrome-related immunodeficiency may predispose to renal fungal infections like bezoars and abscesses.
• Cholestatic liver injury might induce interlobular bile duct proliferation as an adaptive response.
• The absence of spinal motor neuron degeneration suggests ARC-related amyotrophy stems from impaired synaptic vesicle trafficking, not autophagosome-lysosome fusion defects.