Calcified nodules on fingers in primary hyperoxaluria type 2

Abstract

A 51-year-old man who had been receiving haemodialysis for 15 years was referred to the Toranomon Hospital (Tokyo, Japan) with progressive calcifi ed nodules on his fi ngers. He had been undergoing haemodialysis three times per week, for a total of 12 h per week. The patient had been deemed to have end-stage renal disease of unknown cause. He had undergone a parathyroidectomy 2 years before the referral because he was believed to have progressive extraskeletal calcifi cation caused by hyperparathyroidism with constant hypercalcaemia that was refractory to medical treatment; laboratory fi ndings were compatible with secondary hyperparathyroidism. Since the parathyroidectomy, laboratory fi ndings had returned to normal, but the nodules had progressed and made him unable to grip. A family history could not be obtained because the patient was an orphan, but through a careful interview we identifi ed a past medical history of recurrent urolithiasis, which was judged to be the leading cause of the end-stage renal disease. Physical examination showed clubbed fi ngers with exposed calcifi ed masses (fi gure A). Radiography showed prominent bilateral calcifi ed deposits (fi gure B) and nephrocalcinosis. Gas chromatography– mass spectrometry-based plasma metabolomic assessment showed substantially increased concentrations of oxalate (316 μmol/L) and glycerate (50·2 μmol/L; normal is <10 μmol/L for both), but glycolate concentration was almost normal at 13·3 μmol/L (normal is <12 μmol/L), suggesting the possibility of primary hyperoxaluria type 2. Genetic analysis showed a missense mutation, 181G→A (Asp61Asn), of GRHPR in exon 2. We therefore diagnosed the patient as having primary hyperoxaluria type 2 and started intensive haemodialysis (25 h per week, Monday to Friday, for 2 years so far) in preparation for renal transplantation. The patient is currently on a waiting list for renal transplantation. Primary hyperoxaluria type 2 is a rare autosomal recessive disease caused by mutation of GRHPR, the gene encoding the enzyme glyoxylate reductase/hydroxypyruvate reductase, which results in hyperoxaluria, recurrent urolithiasis, progressive nephrocalcinosis, end-stage renal disease, and, eventually, systemic oxalate deposition. Primary hyperoxaluria type 2, especially when associated with renal failure and caused by plasma oxalate concentrations exceeding the supersaturation index of oxalate in plasma (30 μmol/L), should be identifi ed early because severe manifestations, as seen in our patient, can be prevented with early diagnosis, intensive management of dialysis, and timely transplantation.