GATM – Fanconi renotubular syndrome 1

GATM-related Fanconi renotubular syndrome 1 (FRTS1) is a rare autosomal dominant proximal tubulopathy characterized by generalized solute and water wasting with bone disease. To date, FRTS1 has been described in a single unrelated adult female patient with disease onset in infancy and lifelong refractory hypophosphatemic rickets ([PMID:38876250]). Genetic testing identified a novel heterozygous missense variant in GATM, with no additional family segregation reported.

Patient urinary sediment studies demonstrated pathological intramitochondrial aggregation of mutant GATM by electron microscopy and immunofluorescence, supporting a toxic gain-of-function mechanism leading to proximal tubule injury ([PMID:38876250]). These experimental findings link mutant GATM aggregate formation to the clinical phenotype of renal Fanconi syndrome.

Screening for GATM variants should be considered in patients with unexplained Fanconi syndrome, particularly those with resistant hypophosphatemic rickets. Early molecular diagnosis enables targeted surveillance and management.

References

• Clinica chimica acta; international journal of clinical chemistry • 2024 • Complex phenotype in Fanconi renotubular syndrome type 1: Hypophosphatemic rickets as the predominant presentation. PMID:38876250

Evidence Based Scoring (AI generated)