Renotubular Fanconi syndrome type 1 in children: a case series

Renal Fanconi syndrome is a generalized disorder of the proximal convoluted tubule, characterized by non-selective aminoaciduria, glucosuria, low molecular weight proteinuria, phosphaturia, loss of bicarbonates, electrolytes and many other substances. Autosomal dominant Fanconi renotubular syndromes due to a GATM missense-variant, encodes mitochondrial enzyme arginine-glycine amidinotransferase. In total, 36 cases of genetically confirmed Fanconi renotubular syndrome, type 1 have been reported to date from 10 families. In this article, we present the first Russian cases of two unrelated patients with previously undescribed variants c.1076C>T (p.Ser359Phe) and c.1079T>A (p.Met360Lys) in the GATM gene. The first clinical features of the disease with complete Fanconi syndrome were diagnosed in both cases in early childhood. A decrease of renal function was detected in each of cases already during the first examinations, but the rate of progression was different. The patient 1 had a rate of eGFR decline of 0.6 ml/min/1.73 m² per year, whereas patient 2 demonstrated a higher rate of eGFR decline (-2.1 ml/min/1.73 m²/year). Symptomatic therapy resulted in normalization of growth rates and a decrease in the activity of rickets in patient 1. In patient 2, despite the therapy, signs of osteomalacia persisted, and rachitic deformities of the limbs required orthopedic correction.