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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2019  |  Volume : 30  |  Issue : 3  |  Page : 723-725
Adenine phosphoribosyltransferase deficiency and 2, 8-dihydroxyadenine renal stones: A preventable cause of pediatric renal stones and kidney disease


Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India

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Date of Submission05-Jun-2018
Date of Acceptance06-Aug-2018
Date of Web Publication26-Jun-2019
 

   Abstract 


Adenine phosphoribosyltransferase deficiency is an inherited condition presenting from infancy to late adulthood. The common features are recurrent kidney and urinary tract stones and obstructive symptoms. The stones are characteristically radiolucent. 2, 8-Dihydroxyadenine (2, 8-DHA) formation is blocked by xanthine oxidase blocker allopurinol. Here, we report the case of an eight-month-old baby girl who presented with obstructive acute kidney injury secondary to calculi which was treated with surgical removal of stone. The analysis of the calculi revealed 2, 8-DHA crystals.

How to cite this article:
Parikh MD, Konnur A, Gang S. Adenine phosphoribosyltransferase deficiency and 2, 8-dihydroxyadenine renal stones: A preventable cause of pediatric renal stones and kidney disease. Saudi J Kidney Dis Transpl 2019;30:723-5

How to cite this URL:
Parikh MD, Konnur A, Gang S. Adenine phosphoribosyltransferase deficiency and 2, 8-dihydroxyadenine renal stones: A preventable cause of pediatric renal stones and kidney disease. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Jul 23];30:723-5. Available from: http://www.sjkdt.org/text.asp?2019/30/3/723/261357



   Case Report Top


An eight-month-old baby girl was brought to the hospital with high-grade fever, diarrhea, abdominal pain, and anuria of two days duration. There was no history of crying during micturition or pedal edema and facial puffi-ness. She was the first product of a non-consanguineous marriage, through full-term normal vaginal delivery, with no peripartum complication and a birth weight of 2.75 kg.

On evaluation, she was found to have multiple bilateral renal calculi with 4.5-mm left vesico-ureteric junction calculus and 7.8-mm left renal pelvic calculus, and two calculi were seen involving the renal pelvis and lower calyx of the right kidney with resultant bilateral hydronephrosis. The largest right-sided calculus measured 9.0 mm. On biochemical investigations, her serum creatinine was 5.8 mg/dL and serum bicarbonate was 8.7 mEq/L. Her urine culture showed growth of  Escherichia More Details coli. A diagnosis of acute kidney injury secondary to urosepsis with the underlying bilateral obstructive uropathy was made, and she was treated with intravenous antibiotics along with hydration. A left double J (DJ) stenting and right percutaneous nephrostomy were performed to relieve the obstruction. Her creatinine declined to 0.18 mg/dL over 15 days, with serum bicarbonate being 21.5 mg/ dL and good urine output with resolution of fever. Later, a left ureteroscopy and on the right, a miniperc ureteroscopy and bilateral DJ stenting were done. Her stone was sent for analysis.

One month later, she again presented with asymptomatic recurrent left lower ureteric calculus close to vesico-ureteric junction with no hydroureteronephrosis. She underwent left extracorporeal shock wave lithotripsy with removal of both DJ stents. This time, her renal function remained normal (serum creatinine 0.19 mg/dL) with no evidence of urinary tract infection.

Her stone analysis report revealed stone composition to be of ammonium urate and 2,8-dihydroxyadenine (2, 8-DHA) crystals [Figure 1].
Figure 1: Gross picture of the stone.

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Her metabolic panel workup for stone showed serum calcium levels of 10.4 mg/dL, serum uric acid of 2.8 mg/dL, and serum phosphorus of 5.7 mg/dL.

Her fresh urine sample was collected and sent for analysis to look for crystals. On polarized light, typical Maltese cross-shaped crystals were noticed [Figure 2] and [Figure 3].
Figure 2: Microscopic view of the crysral in urine.

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Figure 3: Maltese cross appearance of the crystal in urine under polarised microscope.

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She was treated with 10 mg/kg/day PO divided doses of allopurinol. In the absence of serum adenine level estimation, we planned to titrate the dose clinically.


   Discussion Top


2, 8-DHA urolithiasis is the result of a metabolic abnormality due to the deficiency of the enzyme, adenine phosphoribosyltransferase (APRT), a salvage enzyme present in all human cells.[1]

APRT catalyzes the formation of adenine mono-phosphate from adenine in the presence of phosphoribosyl pyrophosphate. In the absence of APRT, adenine is metabolized by xanthine oxidase to 2, 8-DHA via the intermediate, 8-hydroxyadenine. 2, 8-DHA is excreted by the kidneys and is insoluble in urine at any range of physiological pH, resulting in 2, 8-DHA crystalluria and urolithiasis.[1]

Features and severity vary greatly affected individuals even among family members. Nearly 15%–20% of people with APRT deficiency present no symptoms. The reported frequency was 1:27,000 people in Japan, and rarer in Europe (1:50,000–100,000 people). Inheritance is autosomal recessive typically involving chromosome 16q24 and has presently 24 functional known mutations.[2]

APRT deficiency is an inherited condition presenting from infancy to late adulthood. The common features are recurrent kidney and urinary tract stones and obstructive symptoms. In infancy, it presents as a tiny ravel of reddish brown material in baby diapers. Renal functions affected by early to late adulthood. Sixty to seventy-five percent of patients are affected in adulthood by this condition, while the median age is 37 years. The presenting symptoms are stones, urinary tract infections, hematuria, abdominal pains, and nausea and vomiting.[3]

  1. There are two types of deficiencies in enzyme: APRT 1 deficiency: It is characterized by absent enzyme levels, usually found in Caucasian populations, with 0.4%–1.1% distribution in the general population[3]
  2. APRT 2 deficiency: It is characterized by decreased levels of enzyme by 10%–25%, usually found in Japanese population, with 5%–1.2% distribution in the general popu-lation[3]


The identification of DHA in stone or urine is pathognomonic of APRT deficiency. Tests available for the diagnosis of APRT deficiency are stone analysis, urine microscopy, renal biopsy, APRT activity, and molecular genetic testing. The stones are characteristically radio-lucent and therefore, have to be differentiated from uric acid stones which are also radio-lucent and have identical chemical reactivity. They have rough and humpy surface and a reddish-brown color that turns gray when drying. The stone is friable, and sections show porosities and were of beige to brown color. Infrared spectrophotometry (IRS) provides characterization of the composition of crystals and confirms the diagnosis. Measurement of enzyme activity in red blood cell lysates is a useful tool for the diagnosis of APRT deficiency. Under polarized light microscope, 2, 8-DHA crystals in urine appear with a central Maltese cross-shaped appea-rance.[4]

2, 8-DHA formation is blocked by xanthine oxidase blocker allopurinol. Adenine is then predominantly excreted in urine and is soluble in urine. The dose of adenine is 300 mg/day in adults and 10 mg/kg/day in children in the absence of renal failure. Increased fluid intake is advisable.

Conflict of interest: None declared.



 
   References Top

1.
Sahota AS, Tischfield JA, Kamatani N, Simmonds HA. Adenine phosphoribosyl-transferase deficiency and 2, 8-dihydroxyadenine lithiasis. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Vogelstein B, Childs B, editors. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001. p. 2571-84.  Back to cited text no. 1
    
2.
Ceballos-Picot I, Daudon M, Harambat J, Bensman A, Knebelmann B, Bollée G. 2,8-dihydroxyadenine urolithiasis: A not so rare inborn error of purine metabolism. Nucleo-sides Nucleotides Nucleic Acids 2014;33:241-52.  Back to cited text no. 2
    
3.
Simmonds HA. Adenine phosphoribosyl-transferase deficiency. Orphaned Encyclopedia July 2003.  Back to cited text no. 3
    
4.
Bollée G, Daudon M, Ceballos-Picot I. Adenine phosphoribosyltransferase deficiency: Leave no stone unturned. World J Clin Urol 2014;3:218-26.  Back to cited text no. 4
    

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Correspondence Address:
Mital Dipakkkumar Parikh
Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat
India
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DOI: 10.4103/1319-2442.261357

PMID: 31249241

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    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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