Symptoms and progression of AKU

Early signs

The earliest and most distinctive sign of AKU is often noticed in infancy, when a baby's nappy or urine darkens on standing, particularly if it is alkaline or left exposed to air for some time. This darkening happens because homogentisic acid in the urine oxidises and turns a dark brown or black colour. In many cases this early sign is subtle and may not be noticed at all, meaning the condition can go unrecognised for years.

Changes during adulthood

Because homogentisic acid accumulates gradually in connective tissue, most of the symptoms associated with AKU become noticeable in adulthood rather than childhood. Pigment deposits build up slowly in cartilage and other connective tissues, a process known as ochronosis. This can cause visible darkening of the ears and sometimes the sclera, the white part of the eyes, as pigment accumulates in cartilage and connective tissue there.

Joint and bone effects

One of the most significant long term effects of AKU is on the joints. Pigment deposition in cartilage makes it more brittle and prone to wear, which can lead to a form of arthritis that typically affects the spine and large joints such as the hips, knees and shoulders. Over time this joint damage can cause stiffness, reduced mobility and chronic pain, and may eventually require joint replacement surgery in some individuals.

Spinal involvement is a particularly common feature, and people with AKU often experience changes in the discs and joints of the back years before equivalent changes appear in the general population.

Heart and blood vessel changes

Pigment can also be deposited in heart valves and blood vessel walls over time. This may contribute to valve stiffening or other cardiovascular changes later in life. Because these changes develop slowly, they are not usually apparent in younger people with AKU and tend to become more relevant with increasing age.

Other tissues

Pigment deposits have also been described in other tissues, including tendons, ligaments and in some cases the kidneys, where they may be associated with the formation of kidney stones. Skin pigmentation, particularly in areas of skin overlying cartilage such as the ears, is another recognised feature.

Variation between individuals

The rate and severity of symptom progression can vary from person to person. Some individuals experience significant joint problems relatively early in adult life, while others have a slower progression. This variability makes it difficult to predict exactly how the condition will unfold for any one person, which is part of why ongoing monitoring is generally recommended rather than relying on symptoms alone.

Why early recognition matters

Because many of the serious effects of AKU take years or decades to develop, recognising the condition early, ideally through family history or testing in infancy, allows for monitoring of joints, heart and other systems before major symptoms appear. This does not change the underlying genetic cause, but it can support earlier and more informed discussions with healthcare providers about managing the condition as it progresses.

The next page looks at how AKU is diagnosed and the main approaches used to manage it over time.