Ophthalmic Manifestations of Primary Oxalosis

Br J Ophthalmol: first published as 10.1136/bjo.64.10.782 on 1 October 1980. Downloaded from British Journal of Ophthalmology, 1980, 64, 782-788 Ophthalmic manifestations of primary oxalosis A. R. FIELDER,' A. GARNER,2 AND T. L. CHAMBERS' From the 'Derbyshire Children's Hospital, Derby, and the 2Department of Pathology, Institute of Ophthalmology, London SUMMARY The clinical and pathological findings of a 6-month-old infant with primary oxalosis, who died in renal failure, are presented. The oxalate crystalline deposition in the retinal pigment epithelium corresponded to the flecked retinopathy observed ophthalmoscopically. The difficulties in establishing a precise biochemical diagnosis are discussed and the relevant ophthalmic literature is reviewed. Oxalate is an end product of metabolism which can Leucocyte D-glyceric dehydrogenase has been be removed from the body only by the kidney. found to be deficient in 4 patients with this disorder, Therefore, if the total body oxalate increases, leading through the action of lactic dehydrogenase whether from increased ingestion of oxalate (or a to increased production and urinary excretion of precursor), hyperabsorption, or increased synthesis L-glycerate from the reduction of hydroxypyruvate.4 of this substance, hyperoxaluria will result, and in The increase in oxalate synthesis is considered to certain circumstances insoluble calcium oxalate in reflect a concomitant oxidation of glyoxylate in the tissues will be deposited to create the condition response to lactic dehydrogenase activity. copyright. known as oxalosis. Although oxalate crystals have Most patients with primary hyperoxaluria present been recognised in urine for over a century, it was in the first few years of life. Renal tract involvement not until the 1950s that the metabolic and hereditary dominates the clinical picture, with nephrolithiasis significance of hyperoxaluria was appreciated, and usually progressing to renal failure and death from at present 2 variants of primary hyperoxaluria are uraemia within 10 years. It is, however, unusual for recognised, both of which are uncommon and this condition to become apparent within the inherited in an autosomal recessive mode. first year of life, only 16 of 105 recorded cases Type I hyperoxaluria is due to a deficiency of the reviewed by Hockaday et al. presenting at this cytoplasmic enzyme oc-ketoglutarate: glyoxylate early age, and many of these presenting atypically.5 http://bjo.bmj.com/ carboligase.1 Normally, under the influence of this The patients with type II hyperoxaluria so far enzyme glyoxylic acid, derived in the first instance reported have run a relatively benign course, from the breakdown of glycine, combines with remaining alive and well for over 15 years.2 ac-ketoglutarate to form oc-hydroxy-3-ketoadipate. Secondary hyperoxaluria may occur in many In its absence, however, glyoxylic acid is diverted conditions, including ingestion of oxalic acid6 or a to form glycolic acid and oxalic acids, the latter precursor such as ethylene glycol,7 8 hyperabsorption being irreversible, with the accummulation and of oxalate following small bowel resection,9 renal on September 30, 2021 by guest. Protected increased urinary excretion of oxalic, glycolic, and, failure,'0-'2 sarcoidosis, and cirrhosis of the liver.'3 at times, glyoxylic acids.2 Although Bourke and Both thiamine and pyridoxine deficiencies cause co-workers3 recently have described a patient with hyperoxaluria in the experimental animal, but high urinary oxalate and glycolate levels, but their role in the production of this state in man has normal oc-ketoglutarate: glyoxylate carboligase acti- yet to be clarified.2 The anaesthetic agent methoxy- vity, these workers used skeletal muscle, whereas flurane, which is also a precursor of oxalic acid may Koch et al.'s' study related to the activity of this cause renal failure,'4 hyperoxaluria,15 and even enzyme in liver, kidney, and splenic homogenates retinal oxalosis.16 (Fig. 1). Type II hyperoxaluria is characterised by a Case report urinary excess of both oxalic and L-glyceric acids. A caucasian male was born on 11 July 1978 with a Correspondence to Mr A. R. Fielder Derbyshire Children's birth weight of 7 lb 15 oz (3600 g) after an unevent- Hospital, North Street, Derby DEI 3BA. ful pregnancy. There was no family history of renal 782 Br J Ophthalmol: first published as 10.1136/bjo.64.10.782 on 1 October 1980. Downloaded from Ophthalmic manifestations ofprimary oxalosis 783 Glycolate O - ketoglutarate Glycine _ G tyoxyateo8-O - keto- hydroxyadipate Fig. 1 Simplified diagram of Serine oxalate metabolism. D-GI)ycerate us- I- Hydroxypyruvate L - Glycerate LGIy-Oxalate Type II hyperoxaluria Type I hyperoxaluria disease, and the other sib, a boy aged 3 years, was Renal biopsy. Glomeruli essentially normal for healthy. Development was normal until the age of age. Almost all proximal tubules were packed with 5 months, when he contracted an upper respiratory large crystalline aggregates, and the associated tract infection. Within a few days he began vomiting epithelial cells were either unidentifiable or degener- copyright. after every feed and was admitted to the Derbyshire ate. Some crystals had broken through the intersti- Children's Hospital 1 month later (4 January 1979) tium and stimulated a fibrotic and chronic inflam- having been anuric for 48 hours. Over the ensuing matory cellular infiltrate. Under partly polarised 20 days peritoneal dialysis was undertaken in 3 light the crystals showed the birefringent pattern of periods for a total of approximately 150 hours. oxalate. The findings were confirmed by electron Despite his poor general condition and age he microscopy. was visually alert on examination and responded to Bone marrow. A specimen obtained from the an opticokinetic stimulus. The anterior segments of http://bjo.bmj.com/ the eyes appeared normal. The posterior poles of both retinae contained numerous minute round white flecks, which did not extend either to the optic disc or beyond the main vascular arcade. These areas were stituated in the deeper retinal layers and appeared as pigment epithelial defects (Fig. 2). Pyridoxine was administered, on an empirical on September 30, 2021 by guest. Protected basis, 50 mg intravenously 6 hourly for 3 days, but unfortunately no clinical improvement was obtained, and the infant, who had by this time been essentially anuric for 3 weeks, died on 24 January 1979. Investigations Blood. Before dialysis: Na 125 mmol/l, K 7-13 mmol/l, Cl 89 mmol/l, Ca 1 26 mmol/l, urea 67 mmol/l, creatinine 1384 Fmol/l. During dialysis: glycolate 23 ,umol/l (normal), oxalate 33 1zmol/l (raised), L-glycerate 6-6 ,umol/I (normal values as yet undetermined but probably normal). Urine. Persistent anuria, no analysis possible. Plain Fig. 2 White flecks in the posterior fundus of the abdominal x-ray showed diffuse nephrocalcinosis. right eye. Br J Ophthalmol: first published as 10.1136/bjo.64.10.782 on 1 October 1980. Downloaded from 784 A. R. Fielder, A. Garner, and T. L. Chambers Fig. 3 Crystalline deposits ofcalcium oxalate in the Fig. 4 Calcium oxalate crystals viewed through pigment epithelium of the posterior retina. partially crossed polarising screens. (Haematoxylin (Haematoxylin and eosin, x 180). and eosin, x 180). anterior iliac crest did not contain any crystalline copyright. deposition. Post-mortem pathology. The kidneys were of normal size (right 40 g, left 35 g) but the tubules were found to be packed with crystals. Crystals were also found in the heart, lung, thymus, thyroid, brain stem, adrenals, pancreas, and testis. OCULAR HISTOPATHOLOGY http://bjo.bmj.com/ The eyes were removed 5 hours after death. There was no discernible external abnormality of either globe. The cornea, iris, ciliary body, and lens were normal and showed no evidence of crystal deposition. The posterior segment tissues were well formed and the retina was in situ. Towards the on September 30, 2021 by guest. Protected posterior pole, however, the retinal pigment epithelium showed several isolated crystalline deposits, which were colourless and birefringent (Figs. 3 and 4). The deposits consisted of sheaths of acicular crystals, and Yasue's stain for calcium oxalate was * positive (Fig. 5). The smaller crystalline deposits were intracellular, whereas larger accumulations Fig. 5 The calcium oxalate crystals are stained black were associated with disruption and degeneration by Yasue's silver-rubeanic acid technique ( x 180). of the pigment epithelium (Fig. 6). Very occasionally crystals were seen within the neuroretina and were Discussion presumed to have migrated from their original location. Some penetration of Bruch's membrane By definition the diagnosis of primary hyperoxa- with encroachment on the choroid was also observed luria rests on the presence, in excess, of urinary in relation to the larger crystals. oxalic and either glycolic or glyceric acids, and in Br J Ophthalmol: first published as 10.1136/bjo.64.10.782 on 1 October 1980. Downloaded from Ophthalmic manifestations ofprimary oxalosis 785 1:- d| .. I. ._ zw ... ... ss Dse ----hur. Fig. 6 Section 1 Fm thick ofAraldite-embedded retina viewed (left) by conventional microscopy and (right) by polarising microscopy, showing a crystalline deposit within the retinal epithelium. (Toluidine blue, x 450). copyright. most instances such measurements can readily be heart,'8 19 thyroid,'8 and testis,'8 with little or no made. In the present case, however, the persistent clinical significance. Heart block due to involve- anuria precluded such estimations. The use of ment of the cardiac conduction tissues has been plasma oxalate levels has proved to be of limited reported,'9220 and presumably the pendular nystag- value, as levels may rise in renal failure unrelated to mus noted by Gottlieb and Ritter2' resulted from oxalosis, though patients with primary hyperoxa- macular involvement. luria tend to have higher concentrations than other So far oxalate deposition in extrarenal tissues has patients with comparable blood ureal' or creatinine'2 been considered in conditions in which there has http://bjo.bmj.com/ levels.

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