Refractory Anaemia with Hyperoxalurea

We report 2 cases of primary hyperoxalurea who presented with refractory anaemia, nephrolithiasis, renal failure warranting repeated renal transplantation in one of the cases. Renal biopsy of the patients revealed crystals of calcium oxalate in the tubules. The same crystals were also visualized in bone marrow biopsy which confirmed the diagnosis of systemic oxalosis. We conclude that Primary hyperoxalurea may rarely cause anemia secondary to calcium oxalate crystal deposition in the bone marrow. DOI : 10.14302/issn.2574-4488.jna-14-614 Corresponding Author: Ayesha Ehsan, Department of Pathology, Fatima Memorial Medical & Dental College, Lahore, Pakistan., Email: ayesha_4@hotmail.com


INTRODUCTION
Primary hyperoxalureas (PHs) are rare inborn errors of glyoxylate metabolism characterized by the overproduction of oxalate, predisposing to hyperoxalurea.Long-standing and unattended hyperoxaluria can progressively impair renal functions, and ultimately lead to renal failure. 1,2Once renal failure occurs, blood oxalate concentrations rise and precipitation occurs throughout the body.This stage is termed "oxalosis."The common extra renal sites of oxalate deposition are the bones, bone marrow, blood vessels, central nervous system, peripheral nerves, retina, skin, and thyroid. 3Renal Failure that ensues in due course of time in almost all the patients of oxalosis, is generally associated with anaemia.Deposition of oxalates in the bone marrow further aggravates anemia and other cytopenias may also be seen. 4re we report the 2 cases of hyperoxalurea who presented with progressive anaemia not responding to therapy with iron, vitamin B12 or folic acid supplements.
Their renal biopsies revealed characteristic oxalate crystals (whewellite crystals).Their bone marrow biopsy demonstrated systemic oxalosis due to underlying PH.

CASE REPORT I
A 30 years old male, resident of Lahore was admitted for opinion regarding the necessity for regular hemodialysis after rejection of second renal transplant.Family history was suggestive of hereditary disease as two of his

CASE REPORT II
A 24 years old male, presented with the complaints of multiple recurrent renal stones bilaterally.He was on dialysis since last 6 months.His brother had died with chronic renal insufficiency secondary to nephrolithiasis.Both the cases we report here showed prominent bone marrow infiltration by these crystals.Crystals were found imbedded in the bone marrow fragments.Occasional giant cell formation was also seen, however, granulomas were not visualised.The blood cytopenias/ anaemia were suggestive of the underlying pathology.Therefore we suggest that the diagnosis of primary hyperoxalurea be kept in mind when patients present with cytopenia and renal failure at an early age.

CONCLUSION:
Primary hyperoxalurea may be a rare cause of anemia secondary to calcium oxalate crystal deposition in the bone marrow.
sisters had died of nephrocalcinosis leading to chronic renal failure at the age of 4 years.Consanguineous marriages in past many generations were also reported.Three cousins of the patient had recurrent stones with normal kidney functions.His past history revealed retention of urine at the age of 5 years due to stone in urethra.Patient presented again after 20 years in 2008 with retention of urine which was relieved by catheterization.Renal ultrasound and X ray KUB reported normal kidneys in both instances.Work up for stone formation was not undertaken at that time.The patient was put on hemodialysis and was planned for transplant which was undertaken in May 2009.After one month, follow up tests revealed Serum Creatinine to be 2.0 mg/dL.Renal Biopsy done in Sep 2009 revealed rejection of transplant.Hemodialysis was started and a second transplant was contemplated.Hemodialysis continued for 2 years till Dec 2011 when second transplant was carried out.A repeat renal biopsy was indicated for increasing serum creatinine.Again transplant rejection was evident on histology.Further investigations revealed Urinary oxalate excretion exceeding 40 mg/day (30 mg Oxalate/gram creatinine).His Blood investigations at the time bone marrow studies revealed bicytopenia with a Haemoglobin of 7.8g/dl, White blood cell count of 5.8 x 10 9 /l; Platelet count of 120 x 10 9 /l.Serum Creatinine was 3.6mg/dl.An attempt to correct the cytopenias by iron, vitamin B12 and folic acid supplements met with failure.No response to anemia could be elicited by adding erythropoietin to the treatment regimen.Renal and bone marrow biopsy were undertaken.Renal biopsy of the patient revealed crystals of calcium oxalate in the tubules (fig I).The same crystals were also visualized in bone marrow aspirate (fig IIa and IIb) and trephine biopsy (fig III).

Fig I :
Fig I: Photomicrograph of renal tissue from case I with a preserved glomerulus and clusters of oxalate crystals in the tubules.