Increased urolithiasis in patients with alkaptonuria in childhood.

Abstract

To the Editor: There are reports on urolithiasis in alkaptonuria (AKU) in middle and late adulthood patients, who have already developed the full clinical picture of the disease (1–4). However, the occurrence of this complication in affected children has not been analysed so far. AKU has the world highest incidence in the Slovak Republic (1 in 19000 livebirths from 509192 studied individuals at the AKU Research Centre, Jessenius School of Medicine, University of Martin (5, 6)). Since 1968, when our project started, our centre has registered a total of 207 AKU patients, including 107 who are younger than 15 years of age (6). In the current study, we have included 21 AKU patients (10 males, 11 females), younger than 15 years of age. In all patients, the diagnosis of AKU was initially established by physical examination (7, 8, 5) and confirmed in each case by the examination of urine homogentisic acid (HGA) by a simple ‘dipstick’ test. This test is performed by a filtration paper strip pre-soaked in 10% NaOH solution (9). In a positive ‘dipstick’ test, the sample of urine is analysed chromatographically and when necessary also by quantitative examination of HGA concentrations. Ultrasonographic examination is most useful for the detection of urolithiasis in AKU as it can detect urolithiasis in its earliest stages of development. When ambiguous, a repeated ultrasonographic examination was performed 1 year later and in the case of a normal sonogram after a 3-year period. As a control group, a cohort of 2382 pediatric, ‘non-AKU’ patients, that were referred for routine sonographic examination to the Paediatric Department (University Hospital Martin) with a suspicion of an as yet undetermined urinary tract disorder, was utilized. For consistency, all ultrasonographic examinations were performed by the same specialist (MZ) for the last 7 years. Laboratory examinations consisted of basic urine investigations, including examination of the urine sediment, urine pH, qualitative screening for hereditary metabolic disorders, amino acid chromatography and the determination of mineral excretion. Creatinine, uric acid and quantitative proteinuria were not determined, since applied methods interfere in ‘alkaptonuric’ urine with HGA (10). Patient serum was used for mineralogram, alkaline phosphatases, creatinine and urea examinations. Urolithiasis was detected in 5 of 21 examined AKU patients (23.81%) (Table 1) and in 5 out of 2382 controls (0.21%; pB0.001, x=225.5, 1 DF). In a 12-year-old female AKU patient where we did not detect urolithiasis, the sonographic examination revealed an unilateral multicystic dysplastic kidney. The results of serum and urine examination in AKU patients with urolithiasis were within the normal range. The increased frequency of urolithiasis in AKU patients younger than 15 years (23.81%) suggests careful and repeated ultrasonographic and biochemical examinations for this important complication should start in early childhood.