To the Editor: Primary hyperoxaluria type 1 is a rare inheriteddisease leading to recurrent nephrolithiasis, nephrocalcinosis,systemic oxalosis, and renal failure, ultimately requiring combinedkidney and liver transplantation.1,2 Because of the rarity ofthis disorder, the diagnosis is often missed or delayed by severalyears, especially when the disease first manifests in adulthood,thus depriving patients of the benefits of therapeutic measuresthat have been instituted in a timely manner.2,3 Therefore,any method allowing early diagnosis is eagerly awaited.4 However,although nephrolithiasis is the revealing symptom in the greatmajority of patients with this disease at any age, until nowlittle attention has been paid to the analysis of stones asa possible diagnostic tool.
Over the past 20 years, we analyzed stones obtained from 74patients with a diagnosis of primary hyperoxaluria type 1 establishedon the basis of complete urinary biochemical tests and evidenceof an enzyme defect. In addition to findings on infrared spectroscopy,we examined the morphologic characteristics of the surface andsections of calculi by means of a stereomicroscope.5 All primaryhyperoxaluria type 1 calculi were composed of pure or virtuallypure (>95%) calcium oxalate monohydrate, or whewellite. Ascompared with idiopathic calcium stones with a similarly highwhewellite content, all primary hyperoxaluria type 1 calculishowed very peculiar morphologic characteristics, includinga whitish or pale-yellow surface and a loose, unorganized section,quite different from the dark-brown surface and well-organized,radiating inner structure of common whewellite stones (Figure 1).In addition, scanning electron microscopy confirmed a crystallinestructure in the primary hyperoxaluria type 1 stone that wasdistinct from that of the common type of whewellite stone. Thisunique morphologic characteristic and the ultrastructure ofprimary hyperoxaluria type 1 stones suggest a fundamental differencein the mechanism of stone formation, reflecting the very rapidand permanent crystal formation induced by genetic hyperoxaluria.The peculiar morphologic characteristics of stones consistentlyobserved in patients with primary hyperoxaluria type 1 (andin the two patients with primary hyperoxaluria type 2 whosestones were analyzed at our laboratory) appeared to be pathognomonicfor this cause, since it was never observed in patients withother hyperoxaluric states (including 45 patients with enterichyperoxaluria) or in any patient in whom a calcium stone formedwithout hyperoxaluria. Therefore, such appearance of stonesmight be a valuable indicator of primary hyperoxaluria type1, prompting early comprehensive laboratory evaluation, includingmeasurements of urinary oxalate, glycolate, and glycerate inorder to achieve a definitive diagnosis.
Figure 1. Morphologic Characteristics of a Whewellite Stone in Typical Primary Hyperoxaluria Type 1 and of a Typical, Idiopathic, Common Type of Whewellite Stone.
Panels A, B, and C show a typical whewellite stone from a patient with primary hyperoxaluria type 1. Panels D, E, and F show a typical, idiopathic, common type of whewellite stone. Panels A and D show the stone surfaces on stereomicroscopic examination. Panels B and E show the sections on stereomicroscopic examination, and Panels C and F show the sections on scanning electron microscopy. There is a marked difference between the dense, radiating charcoal-like structure of the common type of stone, and the inhomogeneous, loose structure of the primary hyperoxaluria type 1 stone, with crystal aggregates of various sizes and shapes including curious, characteristic spherical structures of about 50 µm in diameter resembling balls of wool.
On the basis of our positive clinical experience, we proposethat a morphologic examination be performed before compositionalanalysis by means of x-ray diffraction or infrared spectroscopy,since this direct examination constitutes a simple, rapid, andcheap tool that might point toward the early diagnosis of primaryhyperoxaluria type 1. This diagnosis might provide affectedpatients with a better chance to benefit from the early institutionof adequate therapeutic management and might prevent, or substantiallyretard, the consequences of this devastating disease.
Michel Daudon, Ph.D. Paul Jungers, M.D. Necker Hospital 75015 Paris, France michel.daudon{at}nck.aphp.fr
Dominique Bazin, Ph.D. Paris-Sud University 91405 Orsay, France
Supported by the Centre National de la Recherche Scientifiqueand Paris-Sud University.
Leumann E, Hoppe B. The primary hyperoxalurias. J Am Soc Nephrol 2001;12:1986-1993. [Free Full Text]
Hoppe B, Leumann E. Diagnostic and therapeutic strategies in hyperoxaluria: a plea for early intervention. Nephrol Dial Transplant 2004;19:39-42. [Free Full Text]
Lieske JC, Monico CG, Holmes WS, et al. International registry for primary hyperoxaluria. Am J Nephrol 2005;25:290-296. [CrossRef][ISI][Medline]
Daudon M, Bader CA, Jungers P. Urinary calculi: review of classification methods and correlations with etiology. Scanning Microsc 1993;7:1081-1104. [ISI][Medline]
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