Focal Segmental Glomerulosclerosis and Renal Failure Secondary to Protein Kinase C Delta Deficiency in an Adolescent Male

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Introduction: The autoimmune lymphoproliferative syndrome (ALPS)-like condition, Protein Kinase C-delta (PRKCD) deficiency, is associated with a lupus-like presentation, recurrent infections, and reduced B-cell function with hypogammaglobulinemia in addition to prominent lymphadenopathy and splenomegaly. Renal manifestations previously reported include nephrotic syndrome and glomerulonephritis. Focal segmental glomerulosclerosis (FSGS) and significant end-stage renal disease requiring dialysis have not been previously described in those with PRKCD deficiency.Case Study: We describe a now 21-year-old male of Palestinian descent with consanguineous parents who initially presented at 15 months of age with arthritis, splenomegaly, neutrophilic rash, and recurrent fevers. At 7 years of age, the patient was hospitalized with hepatosplenomegaly, diffuse adenopathy, and post-obstructive pneumonitis secondary to hilar adenopathy. He was subsequently given a diagnosis of presumed ALPS, although FAS mutation testing was negative, and started on mycophenolate with improvement in symptomology. He underwent additional comprehensive genetic testing when he was 18 years old with results revealing a novel homozygous PRKCD variant (c. 1872 1 G > A) leading to a presumed donor splice site defect. [Display omitted] Starting at 19 years of age, the patient was noted to have a steadily rising serum creatinine and profound proteinuria. Kidney biopsy revealed chronic immune complex glomerulonephritis with capillary loop and mesangial immune deposits and changes consistent with secondary FSGS. (Figure 1A&B). He was started on an angiotensin-converting enzyme (ACE) inhibitor for antiproteinuric effects, though this was discontinued due to persistent hyperkalemia. A subsequent renal biopsy performed 5 months later in the clinical setting of rapid deterioration of GFR and worsening proteinuria showed worsening FSGS with prominent podocytopathy (Figure 1 C&D). Mycophenolate and IVIG therapy were discontinued given a lack of efficacy and to preserve renal function. Unfortunately, his creatinine continued to rise, and he progressed to end-stage renal disease necessitating dialysis. He is currently being considered for kidney transplantation. ConclusionSevere FSGS leading to renal failure is an uncommon diagnosis in adolescents and has not previously been described in those with PRKCD deficiency. Our case thus broadens the phenotypic and pathologic renal manifestations of the disorder and emphasizes the need for comprehensive multidisciplinary care of individuals affected by ALPS-like conditions.