Late diagnosis of primary hyperoxaluria type III

Abstract

We report the case of a 78-year-old patient with late diagnosis of hyperoxaluria type III (PH3). He developed renal failure after nephrectomy for clear cell papillary renal carcinoma and complained of recurrent urolithiasis for some 30 years, whose aetiology was never identified. Biochemical laboratory investigations of urine and urolithiasis composition revealed marked hyperoxaluria but normal concentrations of urinary glyceric and glycolic acid as well as stones of idiopathic calcium-oxalate appearance. Furthermore, the dietary survey showed excessive consumption of food supplements containing massive amounts of oxalate precursors. However, the persistence of excessive hyperoxaluria after his eating habits was changed leading us to perform molecular genetic testing. We found heterozygous mutations of the recently PH3-associated HOGA1 gene when sequencing PH genes. This is the first description of late diagnosis primary PH3 in a patient with several additional pro-lithogenic factors. This case illustrates the importance of undertaking a complete biological work-up to determine the aetiology of hyperoxaluria. This may reveal underdiagnosed primary hyperoxaluria, even in older patients.

A report from the European Hyperoxaluria Consortium (OxalEurope) Registry on a large cohort of patients with primary hyperoxaluria type 3

“…However, kidney function is not adequately reported in most instances (64% of patients reported in the literature without data) but presumed normal. Between 2010 and 2019, 151 patients were reported (1-38 patients per paper), 5,6,9,10,19,20,[22][23][24][25][26]28,29,[35][36][37][38][39] and a proportion of these patients are included in this paper. Similar to our data, age of diagnosis/disease onset ranged from 1 month to 48 years of life.…”

“…Similar to our data, age of diagnosis/disease onset ranged from 1 month to 48 years of life. Out of the 36% of patients (n ¼ 55), in whom eGFR values were available (18-232 ml/min per 1.73 m 2 ), 1 patient each was in ESKD 9 or in CKD stages 4 to 5, 20 3 patients had CKD stages 2 to 3 (eGFR, 53-61.8 ml/min per 1.73 m 2 ), meanwhile 26 had CKD stages 1 to 2 (47%; eGFR, 77-104 ml/ min per 1.73 m 2 ). This correlated with our analysis, where 32% of patients had normal kidney function, 46% were in CKD stage 1, 16% in CKD stage 2, and 5.4% in CKD stages $3.…”

“…The oldest patient was reported to have stone disease since age 48. 20 Active kidney stone development was found in 47% of adult patients (7 of 15) from whom we were able to obtain stone follow-up (n ¼ 35 adult patients registered).…”

“…The next most common variants were c.569C>T (AF, 8%) and c.944-46delAGG (AF, 5.3%). Eleven novel pathogenic variants were identified (Table 2 5,6,[9][10][11][20][21][22][23][24][25][26][27][28][29] ).…”

Rapid liquid chromatography tandem mass-spectrometry screening method for urinary metabolites of primary hyperoxaluria

“…Outcomes in PH3 are thought to be more favourable although the degree of hyperoxaluria overlaps with PH1 and 2 5 and renal impairment has now been described. 6 The renal damage suffered by PH patients is prompted by both direct oxalate toxicity of the renal tubular cells and indirectly via urolithiasis. The diseases are progressive and can lead to end-stage renal failure, after which systemic oxalosis occurs.…”