Abstract: FR-PO438
Renal Involvement and Novel Kidney Biopsy Findings in a Young Girl With Aicardi-Goutières Syndrome
Session Information
- Pediatric Nephrology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Johnston, James Blain, Montreal Children's Hospital, Montreal, Quebec, Canada
- Bernard, Geneviève, Montreal Children's Hospital, Montreal, Quebec, Canada
- Campillo, Sarah, Montreal Children's Hospital, Montreal, Quebec, Canada
- Millar, Catherine, Montreal Children's Hospital, Montreal, Quebec, Canada
- Bernard, Chantal, Montreal Children's Hospital, Montreal, Quebec, Canada
- Lovett, Audrey, Montreal Children's Hospital, Montreal, Quebec, Canada
- Gaudreault-Tremblay, Marie-Michele, Montreal Children's Hospital, Montreal, Quebec, Canada
Introduction
Aicardi-Goutières Syndrome (AGS) is an inherited type I interferonopathy (IFN) characterized by a spectrum of disease manifestations, including neurologic (e.g. microcephaly, global developmental delay, spastic paresis, dystonia, cerebral calcifications) and systemic manifestations (e.g. hypothyroidism, skin lesions, recurrent fevers). Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 or IFIH1 have been associated with AGS. Clinical presentation is heterogeneous, with variable onset of disease. Renal involvement has only been rarely reported.
Case Description
A 3-year-old girl with a severe phenotype of AGS due to two pathogenic variants in TREX1 had recurrent vomiting, irritability, and generalized panniculitis only partially responsive to prednisolone 1mg/kg/day. While undergoing screening assessment for JAK1/2 inhibitor therapy, she was found to have severe hypertension (136/94mmHg), hypoalbuminemia (20g/L) and nephrotic range proteinuria (urine protein:creatinine 12.5g/g). Renal function was normal. She was initially treated with enalapril, amlodipine, and prazosin. The renal biopsy revealed podocyte hypertrophy, abundant tubuloreticular inclusions and mild immune complex deposition. Despite initial concerns about EBV viremia and transaminitis, the patient was treated with baricitinib (initially 2mg BID, maximal dose reached 2mg TID). Improvement of vomiting, panniculitis, and irritability was observed over 3 months. Proteinuria also significantly improved (urine protein:creatinine 0.24g/g). Prednisolone was successfully weaned, and antihypertensive treatment reduced to enalapril alone. The patient has remained stable for 18 months, without any EBV disease.
Discussion
Renal involvement has not previously been described in association with TREX1 mutations. Biopsy findings were novel, showing mixed features of podocytopathy, scattered immune deposition, and features of vascular lesions rather than one dominant histopathologic pattern. The effectiveness of JAK1/2 inhibitors in IFN with renal involvement has not been definitively established, but case reports have been encouraging. The correlation between JAK1/2 inhibition and clinical improvement in this case supports the use of baricitinib in other interferon-related disorders.