How Hartnup Disease is Diagnosed

Diagnosing Hartnup disease is a multi-step process that moves from looking at symptoms to analyzing the chemical makeup of the urine, and finally, confirming the cause ^[1][2]. Because some symptoms can look like other conditions, precision in testing is essential ^[1][3].

The First Step: Urine Amino Acid Analysis

The most common way to identify Hartnup disease—and the definitive clinical tool for diagnosis—is a test called urine amino acid chromatography ^[4][1]. This test measures the levels of different protein building blocks in the urine.

In Hartnup disease, the hallmark finding is neutral aminoaciduria—meaning the body is losing a specific group of amino acids (neutral ones) that it should be keeping ^[1][5].

The HAA/OAA Ratio: Differentiating the Cause

A challenge in diagnosis is that many different kidney issues can cause amino acids to show up in the urine. For example, Fanconi syndrome causes a “generalized” aminoaciduria where all types of amino acids are lost, along with sugar and phosphate ^[6][7].

To tell the difference, doctors use a specific calculation:

• HAA: Hartnup Amino Acids (the neutral ones like tryptophan) ^[1].
• OAA: Other Amino Acids (those not typically affected by Hartnup) ^[1].

The HAA/OAA ratio helps confirm if the loss is specific to Hartnup. In patients with the disease, this ratio is significantly higher—often around 6.1—whereas in people with other kidney issues, it is usually much lower, around 0.2 ^[1].

Genetic Testing: A Confirmatory Tool

While the urine test is the primary way doctors diagnose the condition, genetic testing can identify the exact underlying cause ^[5][8]. Genetic testing is often considered optional but highly useful for families wanting to confirm the diagnosis or plan for future children.

• SLC6A19 Gene Testing: Doctors look for two mutations in this specific gene ^[5][8].
• Whole-Exome Sequencing (WES): This is a broader test that looks at all the genes in the body, used when a patient has unusual symptoms and the diagnosis isn’t immediately clear ^[2][9].

Conditions That Can Look Like Hartnup

Doctors must rule out “mimics” before finalizing a diagnosis:

• Dietary Pellagra: This is a niacin deficiency caused purely by poor diet. It causes the same rash but does not show the high levels of amino acids in the urine ^[3][5].
• Other Aminoacidurias: Conditions like Cystinuria or Iminoglycinuria involve different transporters and different sets of amino acids ^[4][10].

Diagnostic Completeness Checklist

When reviewing your child’s lab results, check for these key components:

1. [ ] Neutral Aminoaciduria: Does the report note an increase in neutral amino acids (like tryptophan, alanine, and valine)? ^[1]
2. [ ] HAA/OAA Ratio: Was this specific ratio calculated to rule out generalized kidney tubule damage? ^[1]
3. [ ] Normal Glucose/Phosphate: Are these levels normal? (High levels might suggest Fanconi syndrome instead) ^[6]
4. (Optional but helpful) [ ] SLC6A19 Mutation: Has a genetic test confirmed the specific mutation causing the condition? ^[5]

Return to the Home Page or read about Treating and Living with Hartnup Disease.