Homogentisic acid (HGA) is an intermediate in the breakdown (catabolism) of the amino acids tyrosine and phenylalanine. In healthy metabolism, the enzyme homogentisate 1,2-dioxygenase (HGD) converts HGA to the next step in the pathway, so only trace or undetectable amounts appear in urine. Labs measure HGA in a spot urine sample and report it normalized to creatinine (mmol HGA per mol creatinine) to account for urine concentration.
Markedly elevated HGA is a hallmark of alkaptonuria, a rare inherited (autosomal recessive) condition caused by variants in the HGD gene. When HGD activity is low or absent, HGA builds up and is excreted in large amounts. Over years, oxidized HGA can deposit in tissues (ochronosis), contributing to early spine and large-joint osteoarthritis, tendon/ligament issues, heart-valve calcification, and a higher risk of kidney or prostate stones.
Normal/undetectable HGA is expected in most people and supports intact tyrosine metabolism.
Normal / Undetectable: Typical finding; no evidence of excess HGA. No specific action is needed unless symptoms or other organic acids suggest a metabolic issue.
Elevated:
Borderline/near-cutoff: Consider repeat testing on a well-collected first-morning urine to confirm and review pre-analytic factors (hydration, collection, transport).
Clearly/markedly high: Strongly consider alkaptonuria. Your clinician may order targeted quantitative HGA testing, evaluate for clinical signs (e.g., urine darkening on standing, early joint disease), and discuss HGD genetic testing. Diagnosis is not based on one value alone; confirmation is standard.
Infants/children: Diapers or urine that darken on standing or with alkali; later, joint stiffness.
Adults: Early-onset back or large-joint pain, reduced spine flexibility, tendon/ligament problems, bluish-black cartilage discoloration (ears), and history of renal/prostate stones.
Hydration/collection: The creatinine ratio helps, but extremely dilute or concentrated urine can still shift values. Follow collection and shipping instructions closely.
Diet/supplements: Typical dietary tyrosine/phenylalanine does not raise HGA above reference range when HGD function is normal.
Medications/therapies: Nitisinone (used selectively in alkaptonuria) dramatically lowers urinary HGA; it can raise blood tyrosine, so it requires medical supervision and dietary oversight. Always tell the lab and your clinician about current therapies.
Normal/undetectable HGA: No HGA-specific action needed. Interpret alongside symptoms and the rest of the Organic Acids panel.
Borderline elevation:
Repeat the test (first-morning urine, proper handling).
Review collection, medications, supplements.
Discuss whether quantitative HGA and/or genetic counseling/testing is appropriate based on history and family background.
Clearly elevated:
Consult a clinician experienced in inherited metabolic conditions.
Consider confirmatory urine/plasma HGA and HGD genetic testing.
Management is individualized; it may include specialist follow-up for joints/spine/heart, physical therapy and pain strategies, and—in appropriate cases—nitisinone under specialist care.
Support joint health with healthy body weight, muscle strengthening, and low-impact exercise as tolerated.
What it is: A urine marker of the tyrosine/phenylalanine pathway, reported as mmol/mol creatinine.
Normal result: Typical in most people.
High result: Think alkaptonuria—confirm with repeat/quantitative testing and consider HGD genetics.
Carrier detection: Routine urine HGA is not a dependable carrier screen.
Vitamin C: Not proven harmful in alkaptonuria; potential antioxidant role is uncertain—use only within a clinician-guided plan.
Does one high result diagnose alkaptonuria?
No. It’s a strong clue, but clinicians confirm with repeat/quantitative HGA and usually HGD genetic testing.
Can food alone cause high HGA?
Not in people with normal HGD enzyme function. Marked elevations generally reflect enzyme deficiency, not diet.
My urine sometimes looks dark—do I have alkaptonuria?
Many factors can darken urine. The classic sign is urine that darkens on standing, plus a high HGA result. Testing clarifies.
Should my family get tested?
Because alkaptonuria is autosomal recessive, consider genetic counseling if someone in the family is diagnosed.
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An elevated homogentisic acid (HGA) result means more HGA is leaving your body in urine than expected. HGA is a byproduct of breaking down the amino acids tyrosine and phenylalanine. In most people, an enzyme called homogentisate 1,2-dioxygenase (HGD) keeps HGA extremely low. When HGA is clearly high, it raises concern for alkaptonuria, a rare inherited condition caused by changes in the HGD gene. Over time, excess HGA can deposit in tissues (called ochronosis), which is linked to early spine/large-joint arthritis, tendon/ligament problems, heart-valve calcification, and a higher risk of kidney or prostate stones.
Always compare your value to your lab’s reference range and units (mmol/mol creatinine).
Borderline/slightly above range: Can reflect collection issues, hydration, or normal biological variation. Recheck before drawing conclusions.
Markedly elevated: Much more suggestive of alkaptonuria and warrants targeted follow-up.
Urine that darkens on standing (or diapers that darken),
Early-onset back or large-joint pain, reduced flexibility,
Bluish-black discoloration of cartilage (e.g., ears),
Personal or family history of kidney/prostate stones.
Carriers (one HGD variant) usually have normal HGA. A mild elevation is not a reliable way to identify carrier status; genetic testing is the right tool if carrier screening is needed.
Vitamin C doesn’t “worsen” alkaptonuria. It’s been discussed historically as an antioxidant with uncertain clinical benefit. If you’re prone to kidney stones, avoid high-dose supplements unless your clinician advises otherwise.
Repeat to confirm if the elevation is borderline (ideally a first-morning urine, following the lab’s instructions).
If still elevated, ask your clinician about quantitative urine/plasma HGA and HGD genetic testing to confirm or rule out alkaptonuria.
If alkaptonuria is confirmed or strongly suspected:
Discuss care with a specialist familiar with inherited metabolic conditions.
Management may include nitisinone in selected cases (this typically dramatically lowers urinary HGA and requires monitoring of blood tyrosine and diet).
Joint protection: maintain a healthy weight, use low-impact exercise, and consider physical therapy.
Hydration and routine follow-up for stone risk and cardiac/orthopedic health.
Review the rest of your Organic Acids panel and any amino acid testing for context.
Tell your provider about medications/supplements (including any prior or current nitisinone therapy).
Confirm proper collection/transport; extreme dilution or concentration can nudge results even when creatinine-corrected.
Elevated HGA primarily points to impaired tyrosine metabolism; marked elevations strongly suggest alkaptonuria.
Confirm with repeat and targeted testing; consider genetic testing.
Treatment and monitoring are personalized; early recognition helps protect joints, kidneys, and heart over time.
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I have been using Healthmatters.io since 2021. I travel all over the world and use different doctors and health facilities. This site has allowed me to consolidate all my various test results over 14 years in one place. And every doctor that I show this to has been impressed. Because with any health professional I talk to, I can pull up historical results in seconds. It is invaluable. Even going back to the same doctor, they usually do not have the historical results from their facility in a graph format. That has been very helpful.
Karin
Advanced Plan Member since 2020
What fantastic service and great, easy-to-follow layouts! I love your website; it makes it so helpful to see patterns in my health data. It's truly a pleasure to use. I only wish the NHS was as organized and quick as Healthmatters.io. You've set a new standard for health tracking!
Paul
Healthmatters Pro Member since 2024
As a PRO member and medical practitioner, Healthmatters.io has been an invaluable tool for tracking my clients' data. The layout is intuitive, making it easy to monitor trends and spot patterns over time. The ability to customize reports and charts helps me present information clearly to my clients, improving communication and outcomes. It's streamlined my workflow, saving me time and providing insights at a glance. Highly recommended for any practitioner looking for a comprehensive and user-friendly solution to track patient labs!
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2-Hydroxybutyric acid, 2-Hydroxyhippuric acid, 2-Hydroxyisocaproic acid, 2-Hydroxyisovaleric acid, 2-Hydroxyphenylacetic acid, 2-Oxo-4-methiolbutyric acid, 2-Oxoglutaric acid, 2-Oxoisocaproic acid, 2-Oxoisovaleric, 3-Hydroxy-3-methylglutaric, 3-Hydroxyglutaric acid, 3-Indoleacetic acid (IAA), 3-Methyl-2-oxovaleric acid, 3-Methylglutaconic, 3-Methylglutaric acid, 3-Oxoglutaric acid, 4-Cresol, 4-Hydroxybenzoic acid, 4-Hydroxybutyric acid, 4-Hydroxyhippuric acid, 4-Hydroxyphenylacetic acid, 4-Hydroxyphenyllactic acid, 5-Hydroxyindoleacetic acid (5-HIAA), 5-Hydroxymethyl-furoic acid, Acetoacetic acid, Aconitic acid, Adipic acid, Arabinose, Ascorbic acid (Vitamin C), Carboxycitric acid, Citramalic acid, Citric acid, Creatinine, DHPPA (dihydroxyphenylpropionic acid), Dihydroxyphenylacetic acid (DOPAC), Ethylmalonic acid, Fumaric acid, Furan-2,5-dicarboxylic acid, Furancarbonylglycine, GABA, Glutaric acid (Vitamin B2), Glyceric acid, Glycolic acid, Hippuric acid, Homogentisic acid, Homovanillic acid (HVA), HPHPA (3-(3-hydroxyphenyl)-3-hydroxypropionic acid), HVA/DOPAC, HVA/DOPAC Ratio, Kynurenic acid, Lactic acid, Malic acid, Malonic acid, Mandelic acid, Methylcitric acid (Vitamin H), Methylmalonic acid (Vitamin B12), Methylsuccinic acid, N-Acetylaspartic acid, N-Acetylcysteine acid, Orotic acid, Oxalic acid, Pantothenic acid (Vitamin B5), Phenyllactic acid, Phenylpyruvic acid, Phosphoric acid, Pyridoxic acid (Vitamin B6), Pyroglutamic acid, Pyruvic acid, Quinolinic acid, Quinolinic acid/5-HIAA, Sebacic acid, Suberic acid, Succinic acid, Tartaric acid, Thymine, Tricarballyic acid, Uracil
