Extensive prostatic calculi in alkaptonuria: An unusual manifestation of rare disease

Department of Urology,Amrita Institute of Medical Sciences and Research Centre,Ponekkara, P.O Kochi,Kerala,India

CASE REPORT

Extensive prostatic calculi in alkaptonuria: An unusual manifestation of rare disease

Gaurav Sali*,Appu Thomas,Ginil Kumar,Balagopalan Nair, Kalvampara Sanjeevan,Georgie Mathew,Kannan Nair

Department of Urology,Amrita Institute of Medical Sciences and Research Centre,Ponekkara, P.O Kochi,Kerala,India

Extensive prostatic calculi in a young man should always elicit the suspicion of alkaptonuria.Although prostatic calculi are seen in chronic prostatitis,chronic pelvic pain syndrome and benign prostate hyperplasia,none of these have prostatic calculi or calcif i cation as extensive as in alkaptonuria.A 36 years young man who had severed obstructive lower urinary tract symptoms with extensive prostatic calculi was found to be alkaptonuric on further evaluation.

Alkaptonuria;

Calculi;

Lower urinary tract symptoms;

Prostate;

Young

1.Introduction

Alkaptonuria is a rare hereditary disease due to inborn error of metabolism in homogentisate 1,2-dioxygenase(HGD) enzyme.This enzyme is involved in the metabolism of the tyrosine.Def i ciency in HGD leads to deposition of homogentisic acid and its oxidized product benzoquinone acetic acid(BQA)in the various tissues called as ochronosis. Ochronosis leads to renal and prostatic calculi,sialolithiasis,cholelithiasis,pigmentationoftheskin, musculoskeletal abnormalities,and cardiac valve calcif ication.We present a case of 36 years man who presented with bothersome lower urinary tract symptoms(LUTS)and was found to be alkaptonuric on further evaluation.

2.Case

A 36 years man presented with severe obstructive LUTS.On digital rectal examination prostate was hard and nodular. Flow was a Qmaxof 2 mL/s for a voided volume of 130 mL and post void residual urine volume of 380 mL.Prostate specif i c antigen(PSA)was 0.393 ng/mL,while X-ray of pelvis showed punctate calcif i cation in the region of pubic symphysis(Fig.1),computerized tomography scan of pelvis showed extensive and well calcif i ed areas into the prostaticparenchyma(Fig.2).On further evaluation,he gave history of passage of dark colored urine and chronic low back ache. He was short statured with kyphotic spine.Osler’s sign (bluish discolouration of sclera)was present(Fig.3). Biochemical analysis of urine showed the presence of homogentisic acid.These f i ndings conf i rmed the diagnosis of alkaptonuria.He underwent transurethtral clearance of prostatic calculi which revealed multiple blackish calculi in prostatic urethra and in prostatic fossa(Fig.4)and clearance of calculi.On biochemical analysis,calculi were composed of calcium oxalate and uric acid.

3.Discussion

Hard prostate is a common manifestation of carcinoma of prostate,but in presence of extensive prostatic calculi and normal PSA level in a young man carcinoma of a prostate should not be serious diagnostic consideration. Prostatic calculi are common with incidence varying from 7.35%[1]to 71%[2]but usually they are asymptomatic and are discovered incidentally.Conditions associated with prostatic calculi are chronic prostatitis,chronic pelvic pain syndrome and benign prostate hyperplasia but none of these have prostatic calculi or calci fi cation as extensive as alkaptonuria.Patients with alkaptonuria have tendency to form stones,because homogentisic acid may act as a chemical irritant,causing in fl ammation or it is also possible that HGA physically binds to connective tissue and alters the structure and interactions of the macromolecules[3].In alkaptonuria calculi are also formed in kidney,gall bladder,and salivary glands.Although intraprostatic re fl ux of urine containing high levels homogentisic acid may be responsible for extensive calci fi cation in prostate,the exact mechanism is not known.Prostatic calculi is one of the manifestations of alkaptonuria and is reported in two reports[4,5]but they were incidental fi ndings and asymptomatic.There is only one report in which patient with alkaptonuria had a hard prostate clinically mimicking a carcinoma,secondary to the diffuse deposition of calculi[6].In a report by Decramer et al. [7],an alkaptonuric patient had prostatic calculi leading to chronic prostatitis.A thorough search of literature revealed only one case report[8]where patient with alkaptonuria had bothersome LUTS and underwent transurethtral clearance of prostatic calculi but in this report patient was 50 years old.

No treatment modality has been unequivocally demonstrated to reduce the complications of alkaptonuria.Main treatment attempts have focused on preventing ochronosisthrough the reduction of accumulating homogentisic acid. Such commonly recommended treatments include large doses of ascorbic acid(vitamin C)or dietary restriction of amino acids phenylalanine and tyrosine.However,neither vitamin C treatment nor protein restriction(which can be diff i cult to adhere to)has not shown to be effective in clinical studies[9].A potential disease modifying drug, Nitisinone,inhibits 4-hydroxy-phenyl-pyruvate-dioxygenase and decreases formation of HGA and could prevent or slow the progression of disease in alkaptonuria[9],but its eff icacy is yet to be proved.So treatment of alkaptonuria is symptomatic and palliative in early stages with surveillance for cardiac,renal,and prostate complications.This case of alkaptonuria is unique for its presentation with extensive prostatic calcif i cation.Strong clinical suspicion is required to diagnose alkaptonuria.Although,alkaptonuria(also known as black urine disease,black bone disease)is rare disease with incidence of 1 in 250,000 to 1,000,000 of general population[10]thorough history with physical examination is necessary so that this condition would not remain unnoticed.The paucity of published cases could be due to the fact that many cases would have gone unnoticed or not reported.

Conf l icts of interest

The authors declare no conf l ict of interest.

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[10]PhornphutkulC,IntroneWJ,PerryMB,BernardiniI, Murphey MD,Fitzpatrick DL,et al.Natural history of alkaptonuria.N Engl J Med 2002;347:2111e21.

Received 22 February 2015;received in revised form 10 March 2015;accepted 10 June 2015 Available online 25 June 2015

*Corresponding author.

E-mail address:saligaurav@gmail.com(G.Sali).

Peer review under responsibility of Shanghai Medical Association and SMMU.

http://dx.doi.org/10.1016/j.ajur.2015.06.003

2214-3882/a2015 Editorial Off i ce of Asian Journal of Urology.Production and hosting by Elsevier(Singapore)Pte Ltd.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).