Karyomegalic interstitial nephritis with a novel FAN1 gene mutation and concurrent ALECT2 amyloidosis

BACKGROUND: Karyomegalic interstitial nephritis (KIN) is a rare hereditary cause of chronic kidney disease. It typically causes progressive renal impairment with haemoproteinuria requiring renal replacement therapy before 50 years of age. It has been associated with mutations in the Fanconi anaemia-associated nuclease 1 (FAN1) gene and has an autosomal recessive pattern of inheritance. Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is the third most common cause of amyloid nephropathy presenting with chronic kidney disease and variable proteinuria. We report a novel mutation in the FAN1 gene causing KIN and to our knowledge, the first case of concurrent KIN and ALECT. CASE PRESENTATION: We describe the case of 44 year old Pakistani woman, presenting with stage four non-proteinuric chronic kidney disease, and a brother on dialysis. Renal biopsy demonstrated KIN and concurrent ALECT2. Genetic sequencing identified a novel FAN1 mutation as the cause of her KIN and she is being managed conservatively for chronic kidney disease. Her brother also had KIN with no evidence of amyloidosis and is being worked up for kidney transplantation. CONCLUSION: This case highlights two rare causes of chronic kidney disease considered underdiagnosed in the wider population due to their lack of proteinuria, and may contribute to the cohort of patients reaching end stage renal disease without a renal biopsy. We report a novel mutation of the FAN1 gene causing KIN, and report the first case of concurrent KIN and ALECT2. This case highlights the importance of renal biopsy in chronic kidney disease of unclear aetiology which has resulted in a diagnosis with implications for kidney transplantation and family planning.