C3 Glomerulopathy in Autoinflammatory-Pancytopenia Syndrome: A Case Report.

Abstract

Autoinflammatory-pancytopenia syndrome (AIPCS) is a rare autosomal recessive disease caused by a mutation in the deoxyribonuclease II (DNASE2) gene. It has mainly haematological manifestations and recurrent fevers. The kidney could be involved in the form of proteinuria, membranoproliferative glomerulonephritis (MPGN) or immune complex deposition rather than acute kidney injury (AKI) or C3 glomerulopathy (C3G). A six-year-old male child presented with high-grade fever, AKI, generalized edema and hypertension. He had a history of recurrent hospital admission with fever, arthritis, skin rash and recurrent infections in the form of diarrhoea and chest infection. He had stunted growth, pallor, hepatosplenomegaly (HSM) and skin hyperpigmentation at the sites of the healed vasculitic skin rash. He was diagnosed with hemophagocytic lymphohistiocytosis and received its protocol of treatment with improvement of fever. However, pancytopenia and HSM were still progressive. Laboratory investigations revealed pancytopenia, impaired kidney function tests and heavy-range proteinuria with persistent low C3 level. Kidney biopsy revealed C3 deposition suggestive of C3G, with 20% global glomerulosclerosis, mild interstitial fibrosis and tubular atrophy (10%). Kidney function tests normalized after receiving intravenous methylprednisolone, but proteinuria is still persistent, which indicates that AKI was on top of chronic kidney disease in the presence of C3G. Whole exome sequencing revealed a homozygous (missense) variant of uncertain significance with pathogenic evidence in exon-6 of the DNASE2 gene causing AIPCS. In conclusion, C3G is a new form of kidney involvement associated with AIPCS. Kidney histopathology should be combined with phenotypic-genotypic aspects of AIPCS.