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PubMed This is a summary of 14 peer-reviewed journal articles Updated
Nephrology

The Biology of APRT Deficiency and Avoiding the Diagnostic Trap

At a Glance

APRT deficiency is a rare genetic disorder that causes a buildup of adenine, leading to harmful 2,8-DHA kidney stones. Because these stones are invisible on X-rays and closely mimic uric acid, they are frequently misdiagnosed. Proper testing is crucial to prevent kidney damage.

Understanding how adenine phosphoribosyltransferase (APRT) deficiency works is the first step in moving from a frustrating cycle of recurring stones to a manageable health plan. This condition is a metabolic disorder, meaning it stems from a “glitch” in your body’s internal chemistry [1].

The Biological “Glitch”: How Crystals Form

In a healthy body, your cells use a process called the “salvage pathway” to recycle adenine (a natural substance found in your DNA) [2]. An enzyme (a protein that triggers chemical reactions) called APRT is responsible for turning adenine back into a useful form called AMP [3].

When the APRT enzyme is missing or doesn’t work correctly:

  1. Adenine Builds Up: Adenine cannot be recycled, so it accumulates in the blood and urine [4].
  2. The Wrong Enzyme Steps In: Another enzyme, called xanthine oxidoreductase (XOR), tries to break down the excess adenine [1].
  3. The Creation of 2,8-DHA: Instead of a useful substance, XOR turns adenine into 2,8-dihydroxyadenine (2,8-DHA) [4][2].
  4. Insoluble Crystals: 2,8-DHA is highly insoluble, meaning it cannot dissolve in liquid [5]. It quickly turns into hard crystals or stones in the kidneys and urinary tract [6].

The Diagnostic Trap: 2,8-DHA vs. Uric Acid

One of the biggest challenges with APRT deficiency is how easily it is mistaken for more common conditions. This is known as a misdiagnosis trap.

  • Invisible on X-ray: Like uric acid stones, 2,8-DHA stones are radiolucent—meaning they are invisible on standard X-rays [7][5]. They can usually only be seen using a CT scan or ultrasound [8].
  • The Chemistry Mimic: In many laboratories, standard stone analysis is not specialized enough to distinguish 2,8-DHA from uric acid [9][10].
  • Why Misdiagnosis is Dangerous: If a doctor believes you have uric acid stones, they may prescribe treatments that make the urine more alkaline (less acidic). While this helps uric acid stones dissolve, it has no effect on 2,8-DHA [11]. Meanwhile, the “silent” crystals continue to build up, potentially leading to permanent kidney scarring or failure [11][12].

Types of APRT Deficiency

Doctors divide the condition into two types based on how much the APRT enzyme is working:

  • Type I: There is a complete absence of APRT enzyme activity. This type is found in people of all backgrounds [1].
  • Type II: There is a small amount of “residual” enzyme activity still present. This type is primarily found in the Japanese population due to a specific genetic founder effect [13].

Despite these differences, both types lead to the same result: the formation of harmful crystals and the need for the same daily treatment [1][14].

How It Is Inherited

APRT deficiency is an autosomal recessive condition [7]. This means that for a person to have the disorder, they must have inherited two copies of the mutated gene—one from each parent [13].

  • Carriers: Parents are typically “carriers,” meaning they have one healthy gene and one mutated gene. Carriers usually have no symptoms and no risk of developing 2,8-DHA stones.
  • Risk for Siblings: If two carriers have a child, there is a 25% chance with each pregnancy that the child will have APRT deficiency [13]. Because siblings may have the condition without having formed a painful stone yet, doctors often recommend testing them early to prevent future kidney damage. Speaking with a genetic counselor can help families understand testing options.

Common questions in this guide

How do 2,8-DHA crystals form in APRT deficiency?
When the APRT enzyme is missing, your body cannot properly recycle a substance called adenine. A different enzyme tries to break it down but creates an insoluble chemical called 2,8-DHA instead, which quickly forms hard crystals in the kidneys and urinary tract.
Why is APRT deficiency often misdiagnosed?
The 2,8-DHA stones caused by this condition are invisible on standard X-rays and look identical to common uric acid stones in standard laboratory tests. This often leads doctors to prescribe uric acid treatments, which do not stop 2,8-DHA crystal formation.
What is the difference between Type I and Type II APRT deficiency?
Type I involves a complete absence of the APRT enzyme and is found worldwide. Type II involves a tiny amount of leftover enzyme activity and is mostly seen in Japanese populations. Both types cause identical symptoms and require the exact same daily treatment.
How is APRT deficiency inherited?
It is an autosomal recessive condition, meaning you must inherit one mutated gene from each parent to develop the disorder. If both parents are carriers, there is a 25 percent chance with each pregnancy that their child will have the condition.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Is my diagnosis Type I or Type II, and does that change my treatment plan?
  2. 2.How does the xanthine oxidoreductase (XOR) inhibitor stop the production of these crystals?
  3. 3.Should my family members and I meet with a genetic counselor to discuss the implications for future family planning?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (14)
  1. 1

    A rare cause of urolithiasis in an infant: Answers.

    Koyun M, Sancaktar M, Aksoy GK, et al.

    Pediatric nephrology (Berlin, Germany) 2021; (36(7)):2067-2068 doi:10.1007/s00467-020-04910-y.

    PMID: 33459934
  2. 2

    Activation of AMP-Activated Protein Kinase by Adenine Alleviates TNF-Alpha-Induced Inflammation in Human Umbilical Vein Endothelial Cells.

    Cheng YF, Young GH, Lin JT, et al.

    PloS one 2015; (10(11)):e0142283 doi:10.1371/journal.pone.0142283.

    PMID: 26544976
  3. 3

    How a purine salvage enzyme singles out the right base.

    Nagappa LK, Balasubramanian S, Balaram H

    The Journal of biological chemistry 2019; (294(32)):11992-11993 doi:10.1074/jbc.H119.010025.

    PMID: 31399535
  4. 4

    2,8-Dihydroxyadenine nephrolithiasis with chronic kidney disease in children: A case report and review of literature.

    Ramdhani R, Mustafa A, Siregar S, et al.

    Urology case reports 2023; (51()):102623 doi:10.1016/j.eucr.2023.102623.

    PMID: 38074799
  5. 5

    Dihydroxyadenine stone with adenine phosphoribosyltransferase deficiency: A case report.

    Krishnappa P, Krishnamoorthy V, Gowda KK

    Indian journal of urology : IJU : journal of the Urological Society of India 2017; (33(3)):246-248 doi:10.4103/iju.IJU_419_16.

    PMID: 28717278
  6. 6

    A case of 2,8-DHA crystalline nephropathy caused by adenine phosphoribosyltransferase deficiency: diagnosis and treatment.

    Kunou M, Yamaguchi M, Takahashi H, et al.

    CEN case reports 2023; (12(3)):329-334 doi:10.1007/s13730-022-00768-1.

    PMID: 36576711
  7. 7

    Adenine phosphoribosyltransferase deficiency and 2, 8-dihydroxyadenine renal stones: A preventable cause of pediatric renal stones and kidney disease.

    Parikh MD, Konnur A, Gang S

    Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia 2019; (30(3)):723-725 doi:10.4103/1319-2442.261357.

    PMID: 31249241
  8. 8

    [A Case Report of 2,8-Dihydroxyadenine Urolithiasis].

    Miyachi S, Imamura T, Horiuchi E

    Hinyokika kiyo. Acta urologica Japonica 2021; (67(9)):419-421 doi:10.14989/ActaUrolJap_67_9_419.

    PMID: 34610707
  9. 9

    Are conventional stone analysis techniques reliable for the identification of 2,8-dihydroxyadenine kidney stones? A case series.

    Runolfsdottir HL, Lin TL, Goldfarb DS, et al.

    Urolithiasis 2020; (48(4)):337-344 doi:10.1007/s00240-020-01187-6.

    PMID: 32399606
  10. 10

    Recurrence of crystalline nephropathy after kidney transplantation in APRT deficiency and primary hyperoxaluria.

    Bollée G, Cochat P, Daudon M

    Canadian journal of kidney health and disease 2015; (2()):31 doi:10.1186/s40697-015-0069-2.

    PMID: 26380104
  11. 11

    2,8-Dihydroxyadenine Nephropathy Identified as Cause of End-Stage Renal Disease After Renal Transplant.

    George SA, Al-Rushaidan S, Francis I, et al.

    Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 2017; (15(5)):574-577 doi:10.6002/ect.2015.0096.

    PMID: 27447713
  12. 12

    Unusual cause of crystalline nephropathy.

    Gopalakrishnan N, Rajasekar D, Dhanapriya J, et al.

    Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia 2018; (29(2)):462-465 doi:10.4103/1319-2442.229280.

    PMID: 29657221
  13. 13

    Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency.

    Runolfsdottir HL, Sayer JA, Indridason OS, et al.

    European journal of human genetics : EJHG 2021; (29(7)):1061-1070 doi:10.1038/s41431-020-00805-6.

    PMID: 33707627
  14. 14

    Comparison of the effect of allopurinol and febuxostat on urinary 2,8-dihydroxyadenine excretion in patients with Adenine phosphoribosyltransferase deficiency (APRTd): A clinical trial.

    Edvardsson VO, Runolfsdottir HL, Thorsteinsdottir UA, et al.

    European journal of internal medicine 2018; (48()):75-79 doi:10.1016/j.ejim.2017.10.007.

    PMID: 29241594

This page explains the biology and diagnosis of APRT deficiency for educational purposes only. Always consult a nephrologist or urologist for an accurate diagnosis and customized treatment plan.

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