Diagnosis and management of AKU

How AKU is diagnosed

AKU is often first suspected because of the characteristic darkening of urine on standing, particularly if this is noticed in infancy. However, because this sign can be subtle or missed, the condition is sometimes not identified until later in life, when joint symptoms or other features prompt further investigation.

Urine testing

A simple initial test involves observing whether a urine sample darkens over time when left exposed to air, especially if it is made alkaline. This darkening occurs because of the oxidation of homogentisic acid. More specific laboratory tests can measure homogentisic acid levels directly, which provides stronger evidence for the diagnosis than visual darkening alone.

Genetic confirmation

Because AKU is caused by mutations in the HGD gene, genetic testing can confirm a diagnosis by identifying these mutations. This is particularly useful in families where AKU has already been identified, since relatives can be tested to see whether they carry the same gene changes, even before symptoms appear.

Monitoring over time

Once AKU is diagnosed, ongoing monitoring typically focuses on the joints, spine, heart and kidneys, since these are the areas most affected by long term pigment accumulation. Imaging of joints and the spine, along with regular assessment of heart valve function, can help track changes over the years and inform decisions about treatment or surgery if needed.

Approaches to management

Medication

Reducing the amount of homogentisic acid produced in the body is one approach to managing AKU. A medication called nitisinone works by blocking an earlier step in the same metabolic pathway, which reduces the amount of homogentisic acid that builds up. Its use and availability vary between health systems, and decisions about starting treatment are generally made individually, considering age, symptoms and other health factors.

Diet

Because the pathway affected in AKU involves the amino acids tyrosine and phenylalanine, a lower protein diet has sometimes been suggested as a way to reduce the amount of homogentisic acid produced. The practical impact of diet alone is generally considered more limited than medication, and any significant dietary changes are usually discussed with a qualified healthcare provider or dietitian rather than attempted independently.

Pain and joint care

As joint and spinal symptoms develop, management often includes physiotherapy, pain relief strategies and, in more advanced cases, joint replacement surgery for severely affected hips, knees or shoulders. The goal of these interventions is generally to maintain mobility and quality of life rather than to reverse the underlying pigment accumulation, which is not something current treatments are able to undo once it has occurred.

Cardiovascular monitoring

Given the potential for pigment deposition in heart valves, periodic cardiac assessment is often part of long term care for adults with AKU, particularly as they age.

Living with AKU

Because AKU is a lifelong condition with effects that accumulate gradually, many people manage it alongside ordinary daily life for years before symptoms become significant. Support from healthcare providers familiar with rare metabolic conditions, along with realistic expectations about the slow progression of the disorder, can help in planning long term care.

Anyone seeking a diagnosis or treatment for themselves or a family member should consult a qualified healthcare professional, since individual circumstances vary and this page is intended only as general background information.