A case of renal hypouricemia type 1 associated with compound heterozygous URAT1/SLC22A12 variants A209V and F379L: clinical evidence for their pathogenic significance.
Naoyuki Otani, Marie Yamamoto, Tomoaki Takata et al.
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Case in brief
A 69-year-old woman was evaluated for renal dysfunction and hypouricemia. Testing showed serum uric acid of 0.7 mg/dL and a fractional urate clearance (Cua/Ccr) of 60.5%, alongside CKD stage G3b and a renal stone. Genetic analysis found heterozygous URAT1/SLC22A12 variants A209V and F379L, considered likely to be in compound heterozygosity based on the phenotype and previously reported functional impairment. The findings supported renal hypouricemia type 1 associated with this variant combination. Stone-related urinary abnormalities improved during potassium citrate treatment.
What made this case unusual
The case clinically supports the pathogenic significance of the A209V/F379L combination, whose associated phenotype had not been well characterized. Nephrolithiasis and CKD coexisted, although their relationship to excessive urinary urate excretion was presented as a possibility.
Diagnostic / clinical pearl
Marked hypouricemia with excessive urinary urate excretion can point to renal hypouricemia; in this patient, the A209V/F379L URAT1 variant combination supported type 1 disease.
Why it matters
The observed improvement in stone-related urinary abnormalities during potassium citrate treatment suggests urinary alkalization may be beneficial for nephrolithiasis associated with renal hypouricemia.