Autosomal Recessive Alport Syndrome (ARAS)

Autosomal recessive Alport syndrome is an inherited kidney disease caused by changes (variants) in the COL4A3 or COL4A4 genes. These genes make parts of type IV collagen, a structural protein that builds and repairs the kidney’s filtering membrane (the glomerular basement membrane, or GBM). In ARAS, the GBM becomes thin in places and thick and split in other places. This damage slowly reduces the kidney’s filtering power and may lead to blood in urine (hematuria), protein in urine (proteinuria), and later chronic kidney disease. Many people with ARAS also develop sensorineural hearing loss and eye findings such as specific retinal changes; these appear because the same collagen is used in the inner ear and parts of the eye. In ARAS, both sexes are affected equally and often severely, because a child must inherit one non-working gene copy from each parent. NCBI+2ScienceDirect+2

Autosomal recessive Alport syndrome (ARAS) is a rare inherited kidney disease caused by harmful changes in the COL4A3 or COL4A4 genes. These genes code for parts of type IV collagen, a key building block of the glomerular basement membrane—the kidney’s natural filter. Because this collagen is faulty, the filter is weak and leaky. Over time, blood and protein leak into urine, scarring builds up, and kidney function slowly declines. Many people also develop sensorineural hearing loss and eye changes (like anterior lenticonus and retinal abnormalities). In ARAS, a person inherits one faulty copy of the gene from each parent. Early diagnosis matters because starting kidney-protective treatment early can delay kidney failure by many years. PubMed+3NCBI+3PMC+3

Other names

• Autosomal recessive hereditary nephritis

• Autosomal recessive Alport disease

• COL4A3- or COL4A4-related Alport syndrome (biallelic)
  These names all point to the same condition: kidney disease with hearing and eye involvement due to biallelic COL4A3 or COL4A4 variants. NCBI+1

Types

Although Alport syndrome overall has three inheritance patterns (X-linked, autosomal dominant, and autosomal recessive), this article focuses on autosomal recessive. Within ARAS, doctors may describe “types” in several practical ways:

1. By gene:
    • COL4A3-related ARAS
    • COL4A4-related ARAS
   Both cause similar disease because the α3 and α4 collagen chains work together in the GBM. NCBI+1

2. By age at onset/severity:
    • Childhood-onset (early hematuria → proteinuria → kidney function decline)
    • Adolescent/young-adult onset (slower course) ajkd.org

3. By extra-renal features:
    • With hearing and eye findings
    • Without hearing and/or eye findings
   (These features depend on genotype, age, and sex, and may appear later.) IPNA Online

4. By biopsy pattern:
    • Classic EM “basket-weave” GBM
    • Predominantly thin GBM early, progressing to thickened/lamellated GBM ajkd.org+1

Causes

ARAS is genetic. The primary “cause” is having two pathogenic variants affecting type IV collagen α3 or α4 chains. Below are 20, explained simply, covering the main genetic mechanisms and clinically relevant scenarios:

1. Biallelic COL4A3 variants (both copies altered) prevent a normal α3(IV) chain from forming the GBM network. NCBI+1

2. Biallelic COL4A4 variants (both copies altered) impair the α4(IV) chain and the same network. NCBI

3. Homozygous variants (same variant from both parents) are common in consanguinity and often cause early, severe disease. NCBI

4. Compound heterozygous variants (two different harmful variants, one from each parent) also cause ARAS. NCBI

5. Missense variants changing crucial glycine residues in the collagen triple helix destabilize the GBM scaffold. MedlinePlus

6. Nonsense variants introduce a premature stop, leading to no or truncated collagen chain. MedlinePlus

7. Frameshift variants disrupt the code and protein structure, limiting collagen assembly. MedlinePlus

8. Canonical splice-site variants mis-splice RNA, producing faulty collagen chains. MedlinePlus

9. Large deletions/duplications (copy-number variants) remove or duplicate key exons/regions and break collagen function. PMC

10. Deep intronic variants create cryptic splice sites that standard tests can miss without RNA or expanded analysis. PMC

11. Variants in the NC1 domain interfere with collagen chain assembly and GBM network cross-linking. ScienceDirect

12. Founder variants in specific populations raise local ARAS frequency. (Population genetics reports describe clustered COL4A3/COL4A4 changes.) PMC

13. Uniparental isodisomy (rare) can duplicate a single parental pathogenic allele to homozygosity. (Reported rarely across renal genetics.) PMC

14. Parental mosaicism (rare) can explain recurrence in siblings even when parents test “negative” in blood. PMC

15. Digenic COL4A3+COL4A4 inheritance (both genes hit) can mimic ARAS severity by disrupting the same network. PMC

16. Pathogenic burden with modifying variants may shift phenotype toward earlier kidney failure. (Genotype–phenotype correlations discussed in reviews.) ajkd.org

17. Incorrectly classified VUS that are truly pathogenic (re-classification over time) may clarify unexplained ARAS families. PMC

18. Gene-negative but biopsy-positive Alport phenotype can reflect limits of current testing or undiscovered regulatory variants. IPNA Online

19. Carriers (parents) are asymptomatic but can have thin basement membrane hematuria; two carriers can have a child with ARAS. MedlinePlus

20. Pathology cascade (GBM thinning → splitting/lamellation → podocyte stress) is the downstream “cause” of proteinuria and kidney decline. ajkd.org+1

Symptoms and signs

1. Persistent microscopic hematuria: blood detectable on dipstick/microscope, often the first sign in childhood. Medscape

2. Episodes of gross hematuria: tea- or cola-colored urine, sometimes after infections or exercise. Medscape

3. Proteinuria: increasing urine protein as GBM damage worsens. ajkd.org

4. Swelling (edema): puffiness of face/ankles from protein loss and salt/water retention. MedlinePlus

5. High blood pressure: as kidney function drops. MedlinePlus

6. Fatigue and low energy: due to chronic kidney disease and anemia. NCBI

7. Decreasing kidney function (eGFR fall): progressive CKD over years. ajkd.org

8. Sensorineural hearing loss: usually high-frequency first; often starts in school-age years or adolescence. NCBI

9. Difficulty hearing in noisy rooms: a common early complaint related to high-frequency loss. NCBI

10. Eye findings—retinal “dot-and-fleck”: a speckled retina pattern seen on eye exam; usually does not affect vision. EyeWiki

11. Anterior lenticonus: bulging of the front of the lens, which can blur vision and increase astigmatism, more classic in Alport overall. EyeWiki

12. Recurrent nosebleeds or easy bruising are not typical and suggest another problem; this helps doctors think of the right diagnosis. NCBI

13. Family history of blood in urine, kidney failure, hearing loss, or eye changes can be a clue—even if the pattern is not obvious. IPNA Online

14. Normal growth early, slowing later if CKD advances. NCBI

15. No symptoms at first: many children feel well; urine tests pick up the earliest signs. ajkd.org

Diagnostic tests

A. Physical examination 

1. Blood pressure measurement
   High readings suggest kidney injury and guide treatment. Regular monitoring helps track disease activity. MedlinePlus

2. Edema check (ankles, eyelids)
   Swelling indicates protein loss and salt retention; it supports the presence of significant kidney disease. MedlinePlus

3. Growth and weight review
   Faltering growth in children can follow chronic kidney problems; trend lines matter more than single values. NCBI

4. Focused eye and ear screening questions
   Simple office screening about hearing and vision flags who needs formal testing. NCBI

B. Manual/bedside tests 

5. Urine dipstick
   Quickly detects blood and protein in urine; a positive result needs confirmation with lab tests. MedlinePlus

6. Microscopic urinalysis
   Confirms red blood cells and looks for dysmorphic RBCs/casts that suggest glomerular bleeding. ajkd.org

7. Bedside hearing checks (whisper/tuning fork)
   Simple screens can pick up symmetric high-frequency loss and trigger audiology referral. NCBI

8. Visual acuity and handheld slit lamp screening
   Basic screening may note lens or corneal irregularities, prompting full ophthalmology exam. EyeWiki

C. Laboratory & pathological tests

9. Urine albumin-to-creatinine ratio (ACR) / protein-to-creatinine ratio (PCR)
   Quantifies protein loss and tracks response to therapy (ACEi/ARB). ajkd.org+1

10. Serum creatinine and eGFR
    Measures kidney function over time; decline signals progression. ajkd.org

11. Serum electrolytes and bicarbonate
    Assesses CKD complications (e.g., metabolic acidosis). NCBI

12. Complete blood count (CBC)
    Checks for anemia of CKD, which contributes to fatigue. NCBI

13. Genetic testing—NGS panel (COL4A3/COL4A4/±COL4A5)
    The modern gold standard for confirming Alport spectrum and inheritance; can detect single-nucleotide variants and small indels. NCBI+1

14. Copy-number analysis (e.g., MLPA/NGS-CNV)
    Finds exon-level deletions/duplications missed by sequence alone. PMC

15. Kidney biopsy with light microscopy, immunostaining, and electron microscopy (EM)
    Classic ARAS shows GBM thinning, thickening, and lamellation (“basket-weave”) on EM; immunostains may show preserved α5 but altered α3/α4 patterns. Biopsy is especially helpful when genetics are inconclusive. ajkd.org+2PMC+2

16. Skin biopsy (select cases)
    Less useful in ARAS than in X-linked disease; α5 chain staining can be normal in ARAS, helping with differential diagnosis. PMC

D. Electrodiagnostic / formal functional tests 

17. Pure-tone audiometry
    Measures sensorineural hearing loss, often high-frequency first; establishes a baseline and tracks change. NCBI

18. Otoacoustic emissions (OAE) or auditory brainstem response (ABR)
    Objective hearing tests useful in younger children or when audiometry is difficult. NCBI

19. Electroretinography (selected cases)
    Rarely needed, but can document functional retinal involvement in research or atypical cases. EyeWiki

E. Imaging 

20. Renal ultrasound
    Usually normal in early disease; later may show smaller, echogenic kidneys—useful to rule out other causes and to plan care. NCBI

21. Additional eye imaging often helps but is not strictly “radiology”: slit-lamp exam for anterior lenticonus and OCT/fundus photography for dot-and-fleck retinopathy are standard ophthalmic evaluations in Alport care. EyeWiki

Non-pharmacological treatments (therapies & other measures)

Below are practical, patient-friendly steps that improve quality of life and help protect kidneys in ARAS.

1) Early and regular kidney monitoring. Check urine albumin, urinalysis, blood pressure, and eGFR on a schedule set by your clinician. Early detection of albuminuria or rising BP lets you intensify treatment sooner. KDIGO

2) Tight blood pressure control at home. Home BP logs guide medication dosing and sodium goals. Good BP control slows CKD progression across causes. OUP Academic

3) Sodium restriction. Aim for <2 g sodium/day (about <5 g salt/day) unless you have a salt-wasting condition. Lower sodium improves BP and reduces proteinuria. KDIGO+1

4) Adequate—but not excessive—protein. For adults with CKD, target about 0.8 g/kg/day (adapted individually). Too much protein can raise intraglomerular pressure and albuminuria. Work with a renal dietitian. KDIGO

5) Exercise most days. Moderate-intensity physical activity helps BP, metabolic health, and wellbeing in CKD; adapt to energy levels and clinician guidance. ajkd.org

6) Avoid kidney-toxic drugs. Unless a doctor says otherwise, avoid NSAIDs (like high-dose ibuprofen/naproxen), certain contrast dyes, and unproven supplements; ask your clinician before new meds. (General CKD guidance.) KDIGO

7) Hearing care. Hearing aids often work well for Alport-related SNHL; cochlear implants are an option if hearing becomes severe. Start audiology support early to reduce listening fatigue and improve communication. Alport Syndrome Foundation+1

8) Vision care. Regular eye exams can detect anterior lenticonus, cataract, and retinal changes early so that refractive correction or surgical planning can be made in time. PMC

9) Vaccination and infection prevention. People with CKD should stay updated on influenza, pneumococcal, hepatitis B, and other indicated vaccines to reduce infection-related kidney hits. (CKD guideline practice.) KDIGO

10) Metabolic acidosis review. If serum bicarbonate is low, clinicians may consider alkali therapy; monitoring is important so bicarbonate doesn’t overshoot and BP/volume stay stable. KDIGO+1

11) Genetic counseling & family testing. Identify at-risk relatives, clarify inheritance, and plan pregnancies with full information (teratogenicity of RAS blockers in pregnancy requires planning). PMC+1

12) CKD nutrition resources. Diet patterns higher in fruits/vegetables, whole foods, and lower in ultra-processed items support cardiorenal health; potassium targets vary by kidney stage—review with your team. KDIGO

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Drug treatments

There is no single FDA-approved “Alport-specific” medicine yet; therapy targets CKD risk reduction (lower proteinuria/BP, manage complications). The core is one renin–angiotensin system inhibitor (RASi)—either an ACE inhibitor or an ARB—titrated to the maximum tolerated, approved dose. In adults, an SGLT2 inhibitor with a CKD indication can be added when appropriate. Avoid combining ACEi+ARB. Monitor potassium and kidney function closely. OUP Academic+2KDIGO+2

1) ACE inhibitor – Lisinopril (Zestril). ACE inhibitors reduce angiotensin II formation, dilate the efferent arteriole, lower intraglomerular pressure, and cut proteinuria. Typical adult dose range: 10–40 mg once daily, titrated to effect and tolerance; monitor creatinine and potassium after starts and dose increases. Fetal toxicity risk in pregnancy—avoid and counsel on contraception. Label: FDA. FDA Access Data+1

2) ACE inhibitor – Enalapril (Vasotec). Pro-drug converted to enalaprilat; same class benefits on proteinuria/BP. Adult dosing often 5–20 mg twice daily (per label specifics and clinical judgment). Watch for cough, hyperkalemia, and rise in creatinine after initiation. Label: FDA. FDA Access Data+1

3) ACE inhibitor – Ramipril (Altace). ACEI with strong evidence basis for early use in Alport cohorts; dose typically 2.5–10 mg/day in divided or once-daily dosing adjusted to BP and labs; teratogenic—avoid in pregnancy. Label: FDA; Alport data support early ACEI therapy. FDA Access Data+1

4) ARB – Losartan (Cozaar). Blocks AT1 receptor to achieve similar nephroprotective effects if ACEI not tolerated (e.g., cough). Adult doses often 50–100 mg/day (per label); monitor potassium/creatinine. Label: FDA. FDA Access Data

5) ARB – Irbesartan (Avapro). Useful alternative ARB; labeled dose ranges include 150–300 mg once daily; caution with volume depletion; monitor electrolytes/creatinine. Label: FDA. FDA Access Data+1

6) ARB – Valsartan (Diovan). Another ARB option; adult monotherapy starting 80–160 mg once daily and titrate. Do not combine with ACEI. Label: FDA. FDA Access Data

7) SGLT2 inhibitor – Dapagliflozin (Farxiga). FDA-approved for CKD to reduce risk of sustained eGFR decline/ESKD/CV death across broad CKD populations (not Alport-specific). Typical dose 10 mg once daily; check volume status and eGFR thresholds in label. Useful add-on to RASi in eligible adults. Label: FDA. FDA Access Data+1

8) Loop diuretic – Furosemide (Lasix). For edema and BP control when volume overloaded. Dosing individualized (e.g., 20–80 mg and up, per response). Risks: dehydration, electrolyte loss, ototoxicity at high doses—monitor carefully. Label: FDA. FDA Access Data

9) Phosphate binder – Sevelamer carbonate (Renvela). In dialysis-stage CKD, controls high phosphorus to protect bones/vessels. Taken with meals; dose titrated to serum phosphorus. GI side effects common. Label: FDA. FDA Access Data

10) Active vitamin D – Calcitriol (Rocaltrol). For CKD-MBD with secondary hyperparathyroidism; monitor calcium/phosphorus to avoid hypercalcemia. Dose is low microgram amounts (e.g., 0.25–0.5 mcg), individualized. Label: FDA; KDIGO CKD-MBD framework. FDA Access Data+1

11) Erythropoiesis-stimulating agent – Darbepoetin alfa (Aranesp). For anemia due to CKD (dialysis and non-dialysis). Dosing based on weight and hemoglobin targets; avoid overshooting Hb due to thrombotic risk. Label: FDA. FDA Access Data

12) Intravenous iron – Iron sucrose (Venofer). For iron-deficiency anemia in CKD, especially with ESA therapy. Given IV; monitor ferritin, TSAT, and for infusion reactions. Label: FDA. FDA Access Data

Clinical pearls: Use one RAS blocker (ACEI or ARB), at the highest tolerated dose; do not use ACEI+ARB together. If potassium rises, consider diuretics, dietary counseling, or potassium binders rather than stopping RASi prematurely. In appropriate adults, add an SGLT2 inhibitor. These points align with 2024 KDIGO and contemporary CKD practice commentary. OUP Academic+2NephJC+2

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Dietary molecular supplements

Supplements do not replace guideline-directed therapy. Discuss each with your clinician.

Omega-3 fatty acids (fish oil). May improve triglycerides and some vascular measures in CKD; albuminuria results are mixed. Typical doses in trials: ~1–4 g/day EPA+DHA. Use purified products to reduce contaminants. PubMed+1

Vitamin D (cholecalciferol/ergocalciferol) to correct deficiency. Guidelines suggest correcting vitamin D deficiency in CKD like the general population; dosing follows lab values. This supports bone/mineral health and PTH control. PMC

Alkali (sodium bicarbonate) as a nutrient-medicine crossover. For metabolic acidosis (low serum bicarbonate), supervised alkali can improve biochemical balance; monitor BP/volume. Dose individualized to maintain serum bicarbonate in normal range. KDIGO

(If you want a 10-item expanded supplement list with dose ranges, I can add coenzyme Q10, plant protein swaps, fiber strategies, and cautious potassium guidance by CKD stage with citations.)

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Immunity booster / regenerative / stem cell drugs

There are no FDA-approved stem cell or “regenerative” drugs for Alport syndrome. The FDA explicitly warns patients about clinics selling unapproved stem-cell or exosome products; such interventions can cause serious harm (infections, blindness, tumors) and should be avoided outside regulated trials. If you see marketing claims, be cautious and consult your nephrologist. U.S. Food and Drug Administration+1

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Surgical & device procedures

1) Cochlear implant. Considered when hearing loss progresses beyond what hearing aids can help (often ~50–60 dB HL thresholds). Outcomes in Alport patients are generally favorable with careful selection and rehab. MDPI

2) Refractive/ocular surgery (e.g., lens surgery for anterior lenticonus or cataract). Tailored by ophthalmology to restore vision if lens shape or opacity significantly reduces acuity. PMC

3) Arteriovenous fistula creation (for dialysis preparation). For end-stage kidney disease, timely access planning improves dialysis safety and performance. (General CKD practice.) KDIGO

4) Kidney transplantation. Restores kidney function and overall health when ESKD occurs; note that hearing loss does not improve with transplant because inner-ear collagen remains affected. Alport Syndrome Foundation

5) Peritoneal dialysis catheter placement (if PD chosen). A minimally invasive procedure to enable home dialysis; modality choice depends on patient preference, comorbidities, and lifestyle. (General CKD guidance.) KDIGO

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Prevention & lifestyle

1. Start ACEI or ARB early once albuminuria appears, and titrate. PubMed

2. Keep sodium <2 g/day and log intake. KDIGO

3. Exercise most days; keep a healthy weight. ajkd.org

4. Don’t smoke; seek cessation support. (CKD risk.) KDIGO

5. Avoid nephrotoxic drugs unless essential; ask before NSAIDs. KDIGO

6. Treat hypertension to targets your clinician sets. OUP Academic

7. Keep vaccines current (flu, pneumococcal, HepB). KDIGO

8. See audiology & ophthalmology regularly. Alport Syndrome Foundation+1

9. Plan pregnancy with specialists; avoid ACEI/ARB during pregnancy. SpringerLink

10. Share your genetic diagnosis with family for early screening. PMC

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When to see a doctor (red flags)

• New swelling, rising blood pressure, foamy urine, or less urine.

• Sudden worsening hearing or communication difficulty despite aids.

• Blurred vision, halos, or rapid visual changes.

• Dizziness, fainting, chest pain, or shortness of breath.

• Pregnancy or planning pregnancy while on ACEI/ARB or other CKD meds.
  These signs need prompt review to adjust therapy and protect kidneys, hearing, and vision. KDIGO+2Alport Syndrome Foundation+2

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What to eat & what to avoid

• Eat: fresh fruits/vegetables (adjust potassium by stage), whole grains, plant-forward proteins in moderated amounts, unsaturated fats, and high-fiber foods. Work with a renal dietitian to tailor protein and potassium. KDIGO

• Limit/Avoid: added salt (>2 g sodium/day), ultra-processed foods, high-sodium snacks/soups, large red-meat portions, and high-potassium foods if advised (later-stage CKD). KDIGO

• Hydration: follow personalized fluid guidance; more isn’t always better in CKD. KDIGO

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FAQs

1) Is there a cure for ARAS?
No cure yet. But early ACEI/ARB (and in adults, adding an SGLT2 inhibitor when eligible) delays kidney failure by years. PubMed+1

2) Should every ARAS patient take an ACEI or ARB?
In practice, yes—one RAS blocker titrated to the maximally tolerated dose, unless contraindicated. Don’t combine ACEI+ARB. OUP Academic

3) Can I add an SGLT2 inhibitor?
Many adults with CKD are candidates; dapagliflozin is FDA-approved to reduce CKD progression across broad groups (not Alport-specific). Ask your nephrologist about eligibility. FDA Access Data

4) Do hearing aids really help?
Yes—often very effective for Alport-related hearing loss; cochlear implants are considered if loss becomes severe. Alport Syndrome Foundation+1

5) Will a kidney transplant fix my hearing?
No. Transplant helps kidney function but not inner-ear collagen. Alport Syndrome Foundation

6) Are stem-cell or “regenerative” injections available for Alport?
No approved stem-cell drugs for Alport; FDA warns against unapproved regenerative products. U.S. Food and Drug Administration

7) Which diet is best?
A low-salt, kidney-friendly pattern with ~0.8 g/kg/day protein, tailored potassium, and whole foods. Work with a renal dietitian. KDIGO

8) Can supplements replace medicines?
No. Omega-3s and vitamin D can be adjuncts when indicated, but they do not replace ACEI/ARB or SGLT2 inhibitors. PubMed

9) How often should I test urine and blood?
Your clinician will set intervals based on albuminuria and eGFR; testing both urine albumin and eGFR is standard CKD care. KDIGO

10) Can children be treated early?
Yes—data suggest earlier ACEI use (when albuminuria begins) delays dialysis by many years; pediatric dosing and monitoring are specialized. PubMed

11) What about pregnancy?
ACEI/ARB are teratogenic. Plan pregnancy with nephrology and obstetrics, switch meds safely, and monitor BP/albuminuria closely. SpringerLink

12) Does dual RAS blockade work better?
No—do not combine ACEI+ARB due to harm (hyperkalemia/AKI) without added benefit. Use one RASi at maximally tolerated dose. KDIGO

13) What targets should we track?
BP targets are individualized; sodium <2 g/day is broadly suggested; albuminuria reduction is a key success marker. KDIGO

14) Are eye problems common?
Yes—anterior lenticonus, cataract, and macular changes occur; routine eye exams help timing of care. PMC

15) Where can I find trusted patient info?
The Alport Syndrome Foundation offers practical resources on hearing, diet, and care navigation. Alport Syndrome Foundation

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: October 05, 2025.

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