PAX2 Mutation-Related Oligomeganephronia in a Young Adult Patient

Abstract

Oligomeganephronic hypoplasia, commonly referred to as oligomeganephronia (OMN), is a rare pediatric disorder characterized by small kidneys. Histologically a paucity of nephrons is observed which show compensatory enlargement. Hyperfiltration injury leads to end-stage kidney disease. Here we report a 23-year-old Caucasian female patient who presented with a 7-year history of nonnephrotic proteinuria, slow worsening of renal function, normal-sized kidneys, normal blood pressure, healthy weight, and normoglycemia. Evaluation of a kidney biopsy specimen revealed sparsely distributed and markedly enlarged glomeruli (glomerular density 0.63/mm², glomerular diameter 268 µm), focal segmental glomerulosclerosis (FSGS), and 70% effacement of the foot processes. The glomerular basement membrane was normal (mean thickness 285 nm). The genetic analysis of 19 genes known to cause FSGS identified a heterozygous de novo nonsense mutation of PAX2 in exon 4 (NM_003990.3:c.430C>T and NP_003981.2:p.Gln144Ter). Clinical investigations ruled out optic nerve coloboma, hearing loss, and vesicoureteral reflux. Magnetic resonance imaging of the urogenital tract found the uterus to be bicornuate. Based on these data, OMN in nonhypoplastic kidneys and adaptive FSGS related to PAX2 mutation was diagnosed. Her kidney function worsened during the 30-month follow-up (last visit: eGFR-EPI 32 mL/min/1.73 m²) despite angiotensin-converting enzyme inhibitor treatment. To our best knowledge, our patient is the seventh in the English-language literature with a biopsy diagnosis of OMN in an adult, the first observed with normal-sized kidneys, and the first in whom a specific etiologic genetic diagnosis was established. Nonsense PAX2 mutations between the paired domain and the octapeptide domain appear to manifest in renal-limited phenotype.

Keywords: Congenital anomalies of the kidney and urinary tract; Focal segmental glomerulosclerosis; Oligomeganephronia; Paired box protein 2 mutation; Renal coloboma syndrome.