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Calcified nodules on fingers in primary hyperoxaluria type 2
Clinical Picture
Calcified nodules on fingers in a primary hyperoxaluria type 2 Masayuki Yamanouchi, Yoshifumi Ubara, Tatsuya Takayama, Tomiko Kuhara, Kenmei Takaichi
A 51-year-old man who had been receiving haemodialysis for 15 years was referred to the Toranomon Hospital (Tokyo, Japan) with progressive calcified nodules on his fingers. 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 calcification caused by hyperparathyroidism with constant hypercalcaemia that was refractory to medical treatment; laboratory findings were compatible with secondary hyperparathyroidism. Since the parathyroidectomy, laboratory findings 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 identified 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 fingers with exposed calcified masses (figure A). Radiography showed prominent bilateral calcified deposits (figure 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. A
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 identified early because severe manifestations, as seen in our patient, can be prevented with early diagnosis, intensive management of dialysis, and timely transplantation. Contributors MY and YU did the clinical assessment and investigation. MY, YU, and KT were responsible for care of the patient. TK was responsible for the plasma metabolomic assessment. TT was responsible for the sequence analysis. MY and YU prepared the draft of this report, and TT, TK, and KT reviewed and revised the report. All authors approved the final submitted version.
Lancet Diabetes Endocrinol 2015 Published Online November 3, 2015 http://dx.doi.org/10.1016/ S2213-8587(15)00372-1 Nephrology Center, Toranomon Hospital, Tokyo, Japan (M Yamanouchi MD, Y Ubara MD, K Takaichi MD); Okinaka Memorial Institute for Medical Research, Tokyo, Japan (M Yamanouchi, Y Ubara, K Takaichi); Department of Urology, Jichi Medical University, Tochigi, Japan (T Takayama MD); and Japan Clinical Metabolomics Institute, Kanagawa, Japan (T Kuhara PhD) Correspondence to: Dr Masayuki Yamanouchi, Toranomon Hospital, Tokyo 105-8470, Japan m.yamanouchi@toranomon. gr.jp
Declaration of interests We declare no competing interests.
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Figure: Clinical presentation and radiography findings (A) Both hands were swollen, with calcified masses exposed on all fingers. (B) Radiography showed prominent bilateral and symmetrical calcified deposits, predominantly around the terminal phalanges.
www.thelancet.com/diabetes-endocrinology Published online November 3, 2015 http://dx.doi.org/10.1016/S2213-8587(15)00372-1
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Calcified nodules on fingers in a primary hyperoxaluria type 2 Masayuki Yamanouchi, Yoshifumi Ubara, Tatsuya Takayama, Tomiko Kuhara, Kenmei Takaichi
A 51-year-old man who had been receiving haemodialysis for 15 years was referred to the Toranomon Hospital (Tokyo, Japan) with progressive calcified nodules on his fingers. 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 calcification caused by hyperparathyroidism with constant hypercalcaemia that was refractory to medical treatment; laboratory findings were compatible with secondary hyperparathyroidism. Since the parathyroidectomy, laboratory findings 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 identified 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 fingers with exposed calcified masses (figure A). Radiography showed prominent bilateral calcified deposits (figure 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. A
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 identified early because severe manifestations, as seen in our patient, can be prevented with early diagnosis, intensive management of dialysis, and timely transplantation. Contributors MY and YU did the clinical assessment and investigation. MY, YU, and KT were responsible for care of the patient. TK was responsible for the plasma metabolomic assessment. TT was responsible for the sequence analysis. MY and YU prepared the draft of this report, and TT, TK, and KT reviewed and revised the report. All authors approved the final submitted version.
Lancet Diabetes Endocrinol 2015 Published Online November 3, 2015 http://dx.doi.org/10.1016/ S2213-8587(15)00372-1 Nephrology Center, Toranomon Hospital, Tokyo, Japan (M Yamanouchi MD, Y Ubara MD, K Takaichi MD); Okinaka Memorial Institute for Medical Research, Tokyo, Japan (M Yamanouchi, Y Ubara, K Takaichi); Department of Urology, Jichi Medical University, Tochigi, Japan (T Takayama MD); and Japan Clinical Metabolomics Institute, Kanagawa, Japan (T Kuhara PhD) Correspondence to: Dr Masayuki Yamanouchi, Toranomon Hospital, Tokyo 105-8470, Japan m.yamanouchi@toranomon. gr.jp
Declaration of interests We declare no competing interests.
B
L
R
Figure: Clinical presentation and radiography findings (A) Both hands were swollen, with calcified masses exposed on all fingers. (B) Radiography showed prominent bilateral and symmetrical calcified deposits, predominantly around the terminal phalanges.
www.thelancet.com/diabetes-endocrinology Published online November 3, 2015 http://dx.doi.org/10.1016/S2213-8587(15)00372-1
1