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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2018  |  Volume : 29  |  Issue : 4  |  Page : 997-999
Alkaptonuria, a new association of distal renal tubular acidosis

1 Department of Pediatric Nephrology, Hazrat Aliasghar Childrens' Hospital, Iran University of Medical Sciences, Tehran, Iran
2 Department of Pediatric Endocrinology, Hazrat Aliasghar Childrens' Hospital, Iran University of Medical Sciences; Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

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Date of Submission15-Jul-2017
Date of Acceptance16-Aug-2017
Date of Web Publication28-Aug-2018


Alkaptonuria (ALK) is a rare genetic disorder, characterized by binding of ochronotic pigment to the connective tissues in different tissues. This is the first report of a child presented with primary distal renal tubular acidosis associated with ALK. Both disorders were managed by their specific medical treatments, with no further complication.

How to cite this article:
Nickavar A, Azar MR. Alkaptonuria, a new association of distal renal tubular acidosis. Saudi J Kidney Dis Transpl 2018;29:997-9

How to cite this URL:
Nickavar A, Azar MR. Alkaptonuria, a new association of distal renal tubular acidosis. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 Aug 14];29:997-9. Available from: https://www.sjkdt.org/text.asp?2018/29/4/997/239645

   Introduction Top

Alkaptonuria (ALK) is a rare autosomal recessive disorder, characterized by inborn error of tyrosine metabolism. Decreased activity of liver homogentisate 1,2-dioxygenase results in homogentisic acid (HGA) accumulation and production of a melanin-like polymer.[1] It is clinically asymptomatic during childhood and usually presents at 30 years by ochronosis or blue-dark pigmentation of the skin, sclera, and connective tissue, in addition to aortic or mitral valve disorder, hearing loss, and a severe ochronotic spondyloarthropathy at about 50 years.[2] Fatal complications are uncommon and usually result from cardiac disease or progressive renal impairment.[3]

Distal renal tubular acidosis (RTA) is a hereditary disorder, which presents with metabolic acidosis, sensorineural hearing loss, and nephrocalcinosis. Up to our research, this is the first report of ALK associated with distal RTA and managed with specific treatment of both disorders.

   Case Report Top

This is the report of an 8-year-old girl. Consent form was obtained from the parents for this report. The patient was admitted for failure to thrive (body weight = 4300 g), recurrent vomiting, and dehydration at three months of age. Her birth indices were normal. She had a history of gastroesophageal reflux which was managed by medical treatment. Her parents were not blood related and her father had a history of rheumatoid arthritis. Initial blood pressure was 87/56 mm Hg. Laboratory examinations showed hyperchloremic normal anion gap metabolic acidosis, hyponatremia, hypokalemia, and positive urine anion gap with no reducing substance. Serum and urine amino acid chromatography were normal. Laboratory examinations are summarized in [Table 1] and [Table 2]. Renal ultrasound showed mild medullary nephrocalcinosis and a few nephrolithiasis, in favor of distal RTA. Polycitra-K was started for persistent acidosis, with a relative improvement. In addition, her mother aware of occasional dark urine since toilet training. Extensive amounts of homogentisic acid (HGA) was detected in urine by using gas chromatography-mass spectrometry analysis, diagnostic of ALK, and treated with nitisinone to reduce HGA urinary excretion and low tyrosine diet. Subsequently, she developed sensorineural hearing loss and treated with hearing aids. However, RTA continues during these years and treated with alkali therapy. No other manifestations of ALK developed during five years' follow-up period.
Table 1: Serum variables at diagnosis.

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Table 2: Urine variables at diagnosis.

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   Discussion Top

Alkaptonuria is a chronic progressive disorder of HGA metabolism, which is excreted by both glomerular filtration and renal tubular secretion. Diagnosis is made by dark brown urine discoloration, caused by high urinary HGA excretion.

Multiple organs involvement, such as joints, heart, skin, eyes, and kidneys, have been reported in AKU. Renal and urethral calculi might occur at the later stages of this disorder. In addition, secondary amyloidosis has been reported as an uncommon manifestation of ALK.[3],[4],[5] Renal dysfunction is another uncommon and late complication of ALK, which leads to decreased renal excretion and increased parenchymal concentration of HGA.[6],[7] Therefore, the evaluation of renal function has been recommended in extensive or rapidly progressive skin pigmentation in patients with ALK.[8] Renal biopsy shows chronic tubulointerstitial disorder with ochronotic coarse granular pigment deposition, in addition to occasional glomerular sclerosis and connective tissue destruction.[8],[9]

There is no effective treatment for this disorder. Symptomatic therapy, including anti-oxidants, low-protein diet, and high-dose Vitamin C,[1] has been recommended in patients with ochronosis. Nitisinone is the HGA enzyme-producing inhibitor, which reduces HGA urinary excretion, and accumulates the upstream precursor tyrosine.[10] It has been also suggested as an alternative treatment for acute metabolic decompensation of AKU.[4]

Our patient presented with distal RTA during infancy and treated with alkali therapy. ALK was suspected by dark urine, discoloration and confirmed by increased urine HGA excretion. The patient was well treated with specific nitisinone treatment and low tyrosine diet. This is the first report of the association between these two inherited disorders. As renal tubular secretion is important for the elimination of HGA, it is hypothesized that impaired distal tubular function leads to both distal RTA and ALK. It is recommended to consider distal RTA in ALK with intractable metabolic acidosis to prevent its long-term consequences.

Conflict of interest: None declared.

   References Top

Ranganath LR, Jarvis JC, Gallagher JA. Recent advances in management of alkaptonuria (invited review; best practice article). J Clin Pathol 2013;66:367-73.  Back to cited text no. 1
Aquaron R. Alkaptonuria: A very rare metabolic disorder. Indian J Biochem Biophys 2013;50:339-44.  Back to cited text no. 2
Mullan A, Cocker D, Taylor G, Millar C, Ranganath L. Fatal oxidative haemolysis and methaemoglobinaemia in a patient with alkaptonuria and acute kidney injury. Clin Kidney J 2015;8:109-12.  Back to cited text no. 3
Davison AS, Milan AM, Gallagher JA, Ranganath LR. Acute fatal metabolic complications in alkaptonuria. J Inherit Metab Dis 2016;39:203-10.  Back to cited text no. 4
Wolff F, Biaou I, Koopmansch C, et al. Renal and prostate stones composition in alkapto-nuria: A case report. Clin Nephrol 2015;84: 339-42.  Back to cited text no. 5
Faria B, Vidinha J, Pêgo C, Correia H, Sousa T. Impact of chronic kidney disease on the natural history of alkaptonuria. Clin Kidney J 2012;5:352-5.  Back to cited text no. 6
Venkataseshan VS, Chandra B, Graziano V, et al. Alkaptonuria and renal failure: A case report and review of the literature. Mod Pathol 1992;5:464-71.  Back to cited text no. 7
Wyre HW Jr., Alkaptonuria with extensive ochronosis. Arch Dermatol 1979;115:461-3.  Back to cited text no. 8
Kazancioglu R, Taylan I, Aksak F, et al. Alkaptonuria and renal failure: A case report. J Nephrol 2004;17:441-5.  Back to cited text no. 9
Hughes AT, Milan AM, Christensen P, et al. Urine homogentisic acid and tyrosine: Simultaneous analysis by liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2014;963: 106-12.  Back to cited text no. 10

Correspondence Address:
Dr. Maryam Razzaghy Azar
Department of Pediatric Endocrinology, Hazrat Aliasghar Childrens' Hospital, Iran University of Medical Sciences, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.239645

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  [Table 1], [Table 2]

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