Case report: Focal segmental glomerulosclerosis in a pediatric atypical progeroid syndrome

Abstract

Atypical progeroid syndrome (APS) is a rare type of progeroid syndrome mainly caused by heterozygous missense mutations in the LMNA (MIM 150330) gene. APS has heterogeneous clinical manifestations, and its kidney manifestations, particularly in children, are rarely documented. Here, we report the first pediatric case of APS with focal segmental glomerulosclerosis (FSGS). A 10-year-old boy with progeroid features was referred to the nephrology clinic because of hyperuricemia. He had dark skin, protruding eyes, and beaked nose and was very thin, suggesting lipodystrophy. He had been treated for recurrent urinary tract infection during infancy, and liver biopsy for persisting hepatitis showed steatohepatitis. He also had hypertrophic cardiomyopathy (HCMP) with mitral and tricuspid valve regurgitation. Genetic studies were performed considering his multisystem symptoms, and he was diagnosed as having APS according to exome sequencing findings (c.898G > C, p.Asp300His of LMNA). During the first visit to the nephrology clinic, he had minimal proteinuria (urine protein/creatinine ratio of 0.23 mg/mg), which worsened during follow-up. In three years, his urine protein/creatinine ratio and N-acetyl-b-D-glucosaminidase/creatinine ratio increased to 1.52 and 18.7, respectively. The kidney biopsy result was consistent with findings of FSGS, peri-hilar type, showing segmental sclerosis of 1 (5%) glomerulus out of 21 glomeruli. An angiotensin receptor blocker was added to manage his proteinuria. This is the first pediatric report of FSGS in an APS patient with confirmed LMNA defect, who manifested progeroid features, lipodystrophy, HCMP with heart valve dysfunction, and steatohepatitis. Our case suggests that screening for proteinuric nephropathy is essential for managing APS patients since childhood.

Podocytopathies associated with familial partial lipodystrophy due to LMNA variants: report of two cases

“…The pathogenesis of podocytopathies is currently divided into four forms: a) mediated by permeability factors; b) mediated by cytokine direct toxicity, associated or not with apolipoprotein L1 ( APOL1 ) high-risk genotypes; c) mediated by hyperfiltration; and d) caused by genetic disorders ( 18 ). The genetic causes are associated with mutations in podocyte genes that encode proteins that participate in anchoring pedicels between themselves (slit membrane) and the basal membrane, mitochondrial proteins involved in coenzyme Q10 biogenesis, proteins associated with binding and regulation of the actin cytoskeleton, proteins that form the basal membrane ( 18 , 19 ), and proteins that are components of the nuclear envelope, such as lamin A and lamin C, products of the LMNA gene ( 10 , 20 ).…”