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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Nephrology

Confirming the Diagnosis: Understanding Your Tests

At a Glance

APRT deficiency is often misdiagnosed because standard hospital tests mistake 2,8-DHA kidney stones for uric acid stones. Confirming the condition requires specialized stone analysis like mass spectrometry, fresh urine microscopy to spot unique crystals, or genetic testing.

Because APRT deficiency is rare and often mimics more common conditions, confirming the diagnosis requires specific, specialized tests. Standard hospital tests often miss the signs, leading to years of uncertainty [1][2]. This page outlines the specific tools doctors use to move from suspicion to a definitive “yes.”

1. Specialized Stone Analysis

The most common way patients enter the diagnostic process is after passing a kidney stone. However, standard Fourier-transform infrared spectroscopy (FTIR)—the most common method for stone analysis—is often unreliable for identifying 2,8-DHA [1].

To get an accurate result, stones should be analyzed by experts using:

  • X-ray Diffraction: A more precise way to look at the crystalline structure of the stone [3].
  • Mass Spectrometry (GC/MS or UPLC-MS/MS): This “gold standard” chemical analysis can definitively identify 2,8-DHA by its unique molecular weight and properties [4][3].

2. Urine Microscopy: The “Maltese Cross”

One of the fastest clues to APRT deficiency is found in a simple urine sample. When a specialist looks at your urine under a microscope, they look for unique 2,8-DHA crystals. These crystals have a very specific appearance that is pathognomonic—meaning if they are found, it is almost certain the patient has APRT deficiency [5][6].

  • Color and Shape: They appear as small, reddish-brown spheres with dark outlines and tiny spikes (spicules) in the center [5][7].
  • Polarized Light: When viewed under polarized light, these crystals glow with a characteristic “Maltese cross” pattern [8][9].
  • The “Freshness” Rule: For this test to be accurate, the urine must be fresh (not refrigerated) and analyzed quickly, as crystals can dissolve or change shape over time [10]. You may need to ask your doctor how to coordinate dropping off a sample so it is looked at immediately.

3. APRT Enzyme Activity Test

Since the disease is caused by a missing enzyme, doctors can test for the presence of that enzyme directly. This is usually done through a blood test where the APRT enzyme activity is measured in your red blood cells (erythrocytes) [11].

  • In patients with APRT deficiency, this activity is typically either completely absent (Type I) or severely reduced (Type II) [12][13].

4. Genetic Testing

Genetic testing is the most definitive way to confirm the diagnosis and is often used when stone or enzyme tests are unclear [14][1]. By sequencing the APRT gene, doctors look for biallelic mutations—meaning changes in both copies of the gene (one from each parent) [15][16].

This is particularly helpful for family screening, as it can identify siblings who may have the condition but have not yet developed symptoms [14][17].

Your Diagnosis Completeness Checklist

If you are currently undergoing diagnosis, ensure your medical record includes the following to prevent further misdiagnosis:

Test Category What to Look For Why It Matters
Stone Analysis Result explicitly states “2,8-DHA” (not just “uric acid”). Ensures the stone wasn’t misidentified by standard machines [1].
Urine Test Microscopy report mentioning “reddish-brown spherical crystals” or “Maltese cross.” Provides immediate visual evidence of the condition [5].
Blood Work “APRT enzyme activity” levels in red blood cells. Confirms the underlying metabolic cause of the crystals [12].
Genetics Identification of two mutations in the APRT gene. Provides the final genetic “blueprint” of your condition [15].
Imaging CT scan or Ultrasound results. Shows stones that may be invisible on standard X-rays [2].

Common questions in this guide

Why are APRT deficiency kidney stones often misdiagnosed?
Standard stone analysis often misidentifies 2,8-DHA stones as common uric acid stones. Accurate identification requires specialized testing techniques like X-ray diffraction or mass spectrometry.
What do APRT deficiency crystals look like in a urine test?
Under a microscope, 2,8-DHA crystals appear as small, reddish-brown spheres with tiny spikes. When viewed under polarized light, they show a distinct 'Maltese cross' pattern that strongly indicates APRT deficiency.
Why does a urine sample need to be fresh to test for APRT deficiency?
Fresh, unrefrigerated urine is required because 2,8-DHA crystals can dissolve or change shape over time. If the sample sits too long, it makes it difficult for lab technicians to accurately identify the specific crystal shapes.
How does a blood test check for APRT deficiency?
Doctors can use a specialized blood test to measure the APRT enzyme activity directly in your red blood cells. In people with this condition, the enzyme activity is typically either completely absent or severely reduced.
Why might I need genetic testing for APRT deficiency?
Genetic testing confirms the diagnosis by finding mutations in both copies of the APRT gene, which is especially helpful if stone or enzyme tests are unclear. It is also used to screen siblings who may have the condition but have not yet developed symptoms.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Was my kidney stone analyzed using specialized techniques like X-ray diffraction or mass spectrometry, or just standard FTIR?
  2. 2.How do we coordinate with the lab to ensure my urine sample is tested immediately while it is still 'fresh' for the crystal check?
  3. 3.What lab will be performing my APRT enzyme activity test, and how long does it typically take to get results?
  4. 4.If we choose genetic testing, which specific mutations in the APRT gene are being screened?

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 (17)
  1. 1

    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
  2. 2

    Adenine Phosphoribosyltransferase Deficiency: A Rare Cause of Recurrent Urolithiasis.

    Jaffer A, Joyce A, Koenig P, Biyani CS

    Journal of endourology case reports 2017; (3(1)):49-51 doi:10.1089/cren.2017.0015.

    PMID: 28466077
  3. 3

    Urinary 2,8-dihydroxyadenine excretion in patients with adenine phosphoribosyltransferase deficiency, carriers and healthy control subjects.

    Runolfsdottir HL, Palsson R, Thorsteinsdottir UA, et al.

    Molecular genetics and metabolism 2019; (128(1-2)):144-150 doi:10.1016/j.ymgme.2019.05.015.

    PMID: 31378568
  4. 4

    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
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    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
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    Recurrent DHA nephropathy in renal allograft-revisiting clinicopathological aspects of a rare entity.

    Yesodharan J, Seethalekshmy NV, Nair RR

    Indian journal of pathology & microbiology 2021; (64(3)):504-508 doi:10.4103/IJPM.IJPM_441_20.

    PMID: 34341261
  7. 7

    Febuxostat for the Prevention of Recurrent 2,8-dihydroxyadenine Nephropathy due to Adenine Phosphoribosyltransferase Deficiency Following Kidney Transplantation.

    Nanmoku K, Kurosawa A, Shinzato T, et al.

    Internal medicine (Tokyo, Japan) 2017; (56(11)):1387-1391 doi:10.2169/internalmedicine.56.8142.

    PMID: 28566603
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    2,8-dihyroxyadenine (DHA) crystalline nephropathy: A case report.

    Rather JI, Fatima M, Wani MM, et al.

    Clinical nephrology. Case studies 2025; (13()):37-40 doi:10.5414/CNCS111590.

    PMID: 40182129
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    Rare crystalline nephropathy leading to acute graft dysfunction: a case report.

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    PMID: 31752739
  10. 10

    Quantitative UPLC-MS/MS assay of urinary 2,8-dihydroxyadenine for diagnosis and management of adenine phosphoribosyltransferase deficiency.

    Thorsteinsdottir M, Thorsteinsdottir UA, Eiriksson FF, et al.

    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2016; (1036-1037()):170-177 doi:10.1016/j.jchromb.2016.09.018.

    PMID: 27770717
  11. 11

    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
  12. 12

    Obstructive uropathy and severe acute kidney injury from renal calculi due to adenine phosphoribosyltransferase deficiency.

    Chong SL, Ng YH

    World journal of pediatrics : WJP 2016; (12(2)):243-5 doi:10.1007/s12519-015-0073-8.

    PMID: 26684317
  13. 13

    Adenine phosphoribosyl transferase (APRT) deficiency and a novel sequence variant in APRT with phenotypic diversity and a literature review.

    Leow EH, Chong SL, Tan ES, et al.

    Nephrology (Carlton, Vic.) 2023; (28(12)):649-654 doi:10.1111/nep.14232.

    PMID: 37619970
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    Recurrence of 2,8-dihydroxyadenine Crystalline Nephropathy in a Kidney Transplant Recipient: A Case Report and Literature Review.

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    Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadeninuria.

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    Adenine phosphoribosyltransferase (APRT) deficiency: an increasingly recognized disease.

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    Adenine phosphoribosyl transferase deficiency leads to renal allograft dysfunction in kidney transplant recipients: a systematic review.

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This page explains diagnostic tests and stone analysis for APRT deficiency for educational purposes only. Always consult a urologist, nephrologist, or medical geneticist to interpret your specific laboratory and genetic test results.

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