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.1076CT (p.Ser359Phe) and c.1079TA (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.