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To the Editor: An 11-mo-old developmentally normal girl was referred for evaluation of anasarca for the preceding 3 mo. At presentation, she had periorbital, pedal edema, severe ascites, and vulval edema. The weight was 9.3 kg (–1.30 z), length 79 cm (–0.61 z), and head circumference 44 cm (–0.66 z). She had stage 2 hypertension. Investigations showed hemoglobin 10.5 g/dL, leucocyte count 6.9 × 109/L, platelet count 285 × 109/L, blood urea 92 mg/dL, and serum creatinine 3.25 mg/dL. Hypoalbuminemia (2.1 g/dL), hypercholesterolemia (270 mg/dL), and nephrotic-range proteinuria (Up:Uc 5.5) without microscopic hematuria were noted. Ophthalmological evaluation and other systemic examination were unremarkable. She was born at 38 wk gestation as the firstborn to Telugu-speaking third-degree consanguineous parents (birth-weight 2.5 kg). Despite 8 wk of daily prednisolone, she had not attained remission.
We initiated peritoneal dialysis, but she remained anuric and eventually died 18 d later due to multiorgan failure. Renal biopsy could not be performed. Clinical exome sequencing revealed homozygous missense likely-pathogenic variation in exon 6 of ARHGDIA gene (chr17:g.79826865C>G) resulting in amino acid substitution of arginine for glycine (p.Gly168Arg). Prenatal counseling was provided.
Infantile nephrotic syndrome (INS) from India has been characterized by NPHS1, NPHS2, LAMB2, WT1, or PLCE1 gene mutations [1, 2]. ARHGDIA mutations have not been reported in two large Indian series [1, 2] on INS. ARHGDIA mutations in INS have been reported so far in Pakistani [3], Moroccan, and Ashkenazi Jewish communities [4]. These cases had infantile-onset; showed diffuse mesangial sclerosis on renal biopsy; and rapidly progressed to end-stage renal disease (ESRD) or died [3, 4]. ARHGDIA mutations cause Rho-GTPase activation, causing podocyte damage [3, 4]. Unlike some previous cases [4], our patient did not have intellectual disability. Our report of INS due to ARHGDIA gene mutation adds to existing spectrum of genetic mutations in INS from India.
References
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Narayan, A., Karunakar, P., Krishnamurthy, S. et al. Homozygous ARHGDIA Gene Mutation in an 11-Month-Old Infant with Steroid-Resistant Nephrotic Syndrome. Indian J Pediatr 89, 411 (2022). https://doi.org/10.1007/s12098-021-04053-4
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DOI: https://doi.org/10.1007/s12098-021-04053-4