Saudi Journal of Kidney Diseases and Transplantation

: 2016  |  Volume : 27  |  Issue : 6  |  Page : 1283--1284

Primary hyperoxaluria type I importance of pre-transplant genetic screening

Ranga Migara Weerakkody 
 Renal Services, University Medical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka

Correspondence Address:
Ranga Migara Weerakkody
Renal Services, University Medical Unit, National Hospital of Sri Lanka, Colombo
Sri Lanka

How to cite this article:
Weerakkody RM. Primary hyperoxaluria type I importance of pre-transplant genetic screening.Saudi J Kidney Dis Transpl 2016;27:1283-1284

How to cite this URL:
Weerakkody RM. Primary hyperoxaluria type I importance of pre-transplant genetic screening. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2020 Aug 5 ];27:1283-1284
Available from:

Full Text

To the Editor,

Primary hyperoxaluria (PH) is a rare metabolic disorder with autosomal recessive inheritance. Three mutations have been described leading to PH Types I, II, and III. The metabolic defect in PH Type I results from a mutation of alanine-glyoxylate aminotransferase which is found only in the hepatic peroxisomes. Pyridoxine (Vitamin B6) is a cofactor in this chemical pathway. Oxalate (Ox) is excreted in the urine, which leads to nephrocalcinosis and the eventual development of end-stage renal failure (ESRF). [1] As in the case report described in the July 2015 issue of the Saudi Journal of Kidney Diseases and Transplantation by Naderi G et al, PH can be a tricky condition to diagnose, especially when patients present in ESRF. [2]

I am adding my experience in two such cases.

Miss K, a 17-year-old Sri Lankan woman, was referred for management of ESRF. She had extensive nephrocalcinosis and recurrent nephrolithiasis. She was a product of a consanguineous marriage, and her brother had died at the age of 17 from renal disease. On admission, her serum creatinine was 510 μ mol/L, ionized calcium 1.12 mmol/L, and phosphate 1.6 mmol/L. Twenty-four hour urinary Ox excretion was 0.44 mmol/day (reference 0.23- 0.68). She received an ABO-matched-related kidney transplant (mother donor) after 14 months of dialysis. After four months of the transplant, her creatinine levels began rising. Renal biopsy demonstrated tubular necrosis, inflammation, and heavy Ox crystal deposition. A genetic analysis confirmed Type I PH with an 8-base pair deletion (GCTGCTGT) in AGXT gene. Her graft function continued to deteriorate, and after 19 months of post-transplant, she developed ESRF, and recommenced on hemodialysis. Her condition was complicated with recurrent fistula thrombosis, and only access available was a tunneled subclavian line. She had features of cardiac oxalosis, presenting as diastolic dysfunction. In addition, she developed Ox arthropathy and severe osteopenia. She underwent liver transplantation but unfortunately passed away due to complications.

Mr. A, a 15-year-old male, was referred from the pediatrics unit for further management of nephrocalcinosis. He had a serum creatinine level of 140 μmol/L with 24 h urine Ox excretion of 0.65 mmol/day (reference 0.23-0.68). He also has had many episodes of renal colic but never had hydronephrosis or obstructive uropathy. The high normal Ox excretion, and heavy nephrocalcinosis, raised suspicion of PH, and genetic testing was performed to confirm the findings. The diagnosis of PH Type I, with the same 8-base pair deletion found in Miss K's case, was confirmed. He currently has no features suggestive of extrarenal oxalosis, with normal cardiac function and absence of joint symptoms. He is being prepared for a liver transplant.

The median age at initial symptoms of PH Type 1 is 4-7 years in Europe and 13 years in Japan. PH1 has variable presentations: an infantile form, recurrent urolithiasis, and progressive renal failure in childhood or adolescence and late-onset form with occasional stone passage and sometimes ESRD as the first symptom in adulthood. [3] Sri Lankan patients tend to present later with ESRD despite having PH Type 1. The mutation carried by above two patients is rare among Caucasians but commoner among Asians [4] and characterized by lower urinary excretion of Ox. Lower urinary excretion of Ox is well-recognized characteristic, [5],[6] contrary to what Naderi et al, describe in their letter, making diagnosis of PH challenging. Erroneous offering of isolated renal transplantation to these patients results in 100% of recurrence of oxalosis of the allograft. The diagnosis was only apparent after the genetic testing, which is not affordable for many of the sufferers of disease in third world countries.

The definitive treatment is with combined or interval liver-kidney transplantation as Naderi et al describe in their letter to the editor. The prognosis of the combined liver-kidney transplantation has been ever improving, making it a viable option for these patients.

Conflict of interest: None declared.


1Shekarriz B, Stoller ML, Terris MK, Talavera F, Badley FS. Hyperoxaluria. Medscape, WebMD Health Professionals Network, New York; 2011., Last accessed on 25 October 2016.
2Naderi G, Tabassomi F, Latif A, Ganji M. Primary hyperoxaluria type 1 diagnosed after kidney transplantation: The importance of pretransplantation metabolic screening in recurrent urolithiasis. Saudi J Kidney Dis Transpl 2015;26:783-5.
3Harambat J, Fargue S, Acquaviva C, et al. Genotype-phenotype correlation in primary hyperoxaluria type 1: The p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney Int 2010;77:443-9.
4Williams E, Rumsby G. Selected exonic sequencing of the AGXT gene provides a genetic diagnosis in 50% of patients with primary hyperoxaluria type 1. Clin Chem 2007; 53:1216-21.
5Absy MM. Atypical features of primary hyperoxaluria in end-stage renal disease. Am J Nephrol 1991;11:301-4.
6Schillinger F, Mahmoud M, Montagnac R, Collin P, Milcent T. Adult type I primary hyperoxaluria: 2 cases confirmed by liver biopsy at end-stage renal insufficiency. Nephrologie 1990;11:217-21.