Your body needs amino acids to build muscles, create energy, and keep cells healthy. Sometimes, people lose too many amino acids through their urine because of problems with their genes or their environment. Scientists reviewed hundreds of studies to understand why this happens. They found that nine specific genes can cause this problem, and things like vitamin D deficiency, unhealthy gut bacteria, and exposure to heavy metals can make it worse. This research helps doctors understand these rare conditions better and could lead to new treatments that work specifically for each person’s situation.

The Quick Take

  • What they studied: How genetic mutations and environmental factors cause people to lose excessive amounts of amino acids in their urine, a condition that can affect health and protein production in the body.
  • Who participated: This was a review of existing research studies from 1980 to 2025 that included both human patients and animal studies examining aminoacidurias (excessive amino acid loss in urine).
  • Key finding: Scientists identified 9 main genes and over 350 specific gene mutations that can cause amino acid loss in urine. Environmental factors like vitamin D deficiency, unhealthy gut bacteria, and exposure to lead or cadmium also play a role, though genes appear to be the primary cause.
  • What it means for you: If you or a family member has been diagnosed with amino acid loss in urine, understanding whether it’s caused by genes or environmental factors could help doctors create a personalized treatment plan. However, this research is mainly for healthcare providers and researchers at this stage.

The Research Details

Scientists conducted a scoping review, which means they searched through hundreds of published studies to gather all available information about aminoacidurias. They looked at research published between 1980 and 2025 using two major scientific databases (PubMed and Google Scholar). They included studies that examined specific genes, genetic variations, and environmental factors that cause amino acid loss in urine in both humans and animals.

This type of review is like creating a comprehensive map of what scientists already know about a topic. Rather than doing their own experiments, the researchers organized and summarized findings from many other studies to identify patterns and gaps in knowledge. This approach is useful for understanding complex conditions that involve many different factors.

A scoping review is the right approach for this topic because aminoacidurias are rare and complex conditions involving many different genes and environmental factors. By reviewing all existing research together, scientists can see the bigger picture of how these conditions work. This helps identify which factors are most important and where future research should focus. It also helps doctors understand that these conditions aren’t caused by just one thing—they involve a combination of inherited genes and lifestyle or environmental factors.

This review systematically searched major scientific databases and included studies spanning over 40 years, which shows thorough research. The authors identified specific genes and mutations, giving concrete examples of their findings. However, since this is a review of other studies rather than original research, the quality depends on the studies being reviewed. The authors acknowledge that most cases appear to be genetic rather than environmental, which shows they’re being honest about what the evidence actually shows. Readers should know this represents a summary of existing knowledge rather than new experimental data.

What the Results Show

The research identified nine specific genes that, when mutated, can cause excessive amino acid loss in urine. These genes control proteins that act like ‘doorways’ in your kidneys, allowing amino acids to be reabsorbed into your body instead of being lost in urine. When these genes have mutations (changes in their DNA code), the doorways don’t work properly, and amino acids leak out.

The scientists found over 350 different mutations across these nine genes that can cause problems. This large number of mutations explains why aminoacidurias can look different in different people—each person might have a different mutation affecting their amino acid transport.

Beyond genetics, the review also identified environmental factors that can contribute to amino acid loss. These include vitamin D deficiency, problems with gut bacteria (dysbiosis), and exposure to heavy metals like lead and cadmium. However, the evidence suggests that genetic factors are the primary cause, with environmental factors playing a smaller supporting role.

The research revealed that understanding how amino acids are transported in the kidneys is crucial for treating these conditions. Different genes control the movement of different types of amino acids, so a mutation in one gene might cause loss of certain amino acids while another mutation affects different ones. This explains why doctors need to identify which specific gene is mutated to understand what’s happening in each patient. The review also highlighted that environmental factors like diet and exposure to toxins can make genetic conditions worse, suggesting that lifestyle changes might help manage symptoms even when the underlying cause is genetic.

This review builds on decades of research into rare metabolic disorders. Previous studies identified individual genes and mutations one at a time. This comprehensive review brings all that knowledge together in one place, showing that scientists have discovered far more about these conditions than many doctors might realize. The finding that over 350 mutations exist across just nine genes shows how much genetic diversity there is in these rare conditions. The inclusion of environmental factors is relatively newer in the research, as earlier studies focused mainly on genetics. This review suggests that future research should look more carefully at how genes and environment work together.

This review has several important limitations. First, it summarizes other studies rather than conducting new experiments, so the quality of conclusions depends on the quality of those studies. Second, the review doesn’t specify exactly how many patients were studied across all the research reviewed, making it hard to know how rare or common these conditions truly are. Third, while the review identifies environmental factors, it notes that evidence for environmental causes is limited compared to genetic causes. Finally, most research on these conditions comes from developed countries, so we may not know how common they are in other parts of the world. The review also doesn’t provide detailed information about how effective current treatments are or how well people with these conditions do over time.

The Bottom Line

If you have been diagnosed with excessive amino acid loss in urine, work with a genetic counselor or metabolic specialist to determine which gene mutation you have (HIGH confidence that genetic testing is appropriate). Ensure adequate vitamin D intake through diet or supplements, as vitamin D deficiency may worsen the condition (MODERATE confidence). Maintain a healthy gut through balanced diet and consider probiotic foods if recommended by your doctor (MODERATE confidence). Avoid exposure to heavy metals like lead and cadmium by being aware of your environment and occupational exposures (MODERATE confidence). Regular monitoring of amino acid levels in urine and blood can help track disease progression (HIGH confidence).

People with a family history of amino acid loss disorders should be aware of these findings and discuss genetic testing with their doctor. Parents of children diagnosed with aminoacidurias should understand that it’s likely genetic and not caused by anything they did wrong. Healthcare providers treating rare metabolic disorders should use this information to guide genetic testing and counseling. Researchers studying metabolic diseases and kidney function will find this review valuable. People should NOT assume they have this condition based on general fatigue or muscle weakness—aminoacidurias are rare and require specific testing to diagnose.

If you have this condition, genetic testing can provide answers within weeks to months. Once you know which gene is affected, your doctor can create a treatment plan. Environmental changes like improving vitamin D levels may take several months to show effects. Long-term management is typically lifelong, with regular monitoring to ensure amino acid levels stay stable. Some people manage their condition well with dietary changes and supplements, while others may need more intensive treatment. Improvements in symptoms depend on the specific type of aminoacidurias and how well the underlying cause is managed.

Want to Apply This Research?

  • If diagnosed with aminoacidurias, track weekly urine color and clarity (should be pale yellow, not dark), daily protein intake in grams, and vitamin D supplement doses. Log any symptoms like muscle weakness, fatigue, or changes in urine appearance. Record lab test results (amino acid levels) when available.
  • Users can set daily reminders to take vitamin D supplements if deficient, log dietary protein sources to ensure adequate intake, track water consumption to support kidney health, and record any dietary changes recommended by their doctor. The app could send alerts for scheduled lab work and genetic counseling appointments.
  • Establish a baseline by recording current amino acid levels and symptoms. Monthly, review trends in urine appearance and energy levels. Quarterly, compare lab results to previous tests. Annually, assess overall disease progression and medication effectiveness with your healthcare provider. Use the app to share tracked data with your doctor during appointments to inform treatment adjustments.

This research summary is for educational purposes only and should not be used for self-diagnosis or self-treatment. Aminoacidurias are rare medical conditions that require professional diagnosis through blood and urine tests, often including genetic testing. If you suspect you or a family member has excessive amino acid loss, consult with a healthcare provider, nephrologist (kidney specialist), or genetic counselor. The findings in this review represent current scientific understanding but do not constitute medical advice. Treatment decisions should always be made in consultation with qualified healthcare professionals who can evaluate your individual situation. This summary is not a substitute for professional medical diagnosis, treatment, or advice.