Black Bone Disease

About black bone disease?

Black bone disease, also known as Alkaptonuria (AKU) or black urine disease is a rare genetic metabolic disorder that prevents the body from completely breaking down two proteins called tyrosine and phenylalanine, resulting in the build-up of a chemical called homogentisic acid.

AKU is considered a rare disease, only about 1 in 250,000 to 1 million people worldwide are affected by this condition. It affects people equally, irrespective of gender, although people assigned male at birth (AMAB) develop the symptoms sooner and more severely than people assigned female at birth (AFAB).^1,2

Signs and symptoms

Over the years, the homogentisic acid starts to slowly accumulate in the body and turns the tissues into a darker colour. One of the very first early signs of black bone disease is dark-stained nappies as the presence of homogentisic acid in the urine causes it to turn black when exposed to air.

It can build up in almost any area of the body, including the cartilage, tendons, bones, nails, ears, and heart. It stains the tissues dark and causes a wide range of problems.^1,2

Joint and bones

Joint problems start to appear when patients with black bone disease reach their 30s. The disease may progress and cause the cartilage to become brittle and break, leading to joint and spinal damage. Long-standing AKU causes arthritis (chronic joint pain and inflammation), especially in the larger joints and spines.

Early signs of osteoarthritis are noticed, starting with lower back pain and stiffness, followed by knee, shoulder, and hip pain. Joint disease in AKU patients starts early and can progress more rapidly in people AMAB than in people AFAB.^1,2

Ears and eyes

Some signs of AKU can be noticed in the ear and eyes; grey or blue spots are found in the whites of the eyes, while the cartilage of the ear is thickened and turns into a blue, grey, or black colour. The wax of the ear also may be reddish-brown or black.^1,2

Skin and nails

Some AKU patients may have black or blue speckled areas of their skin as a result of the discoloured sweat. The colour changes in the skin are most obvious in exposed areas to the sun and where the sweat glands are present; such as the cheeks and forehead.^1,2

Breathing difficulties

AKU patients may experience some breathing difficulties or shortness of breath; this will happen if the muscles and bones around the lung become stiff, preventing chest expansion.^1,2

Heart, kidney, and prostate problems

AKU can cause heart problems when the homogentisic acid deposits accumulate around the heart valves, causing them to become hard and brittle. To solve this, sometimes valve replacement surgeries are required.

Kidney stones developed in AKU patients, with 50% of affected people being older than 64 years. People AMAB with AKU may also complain of prostate stones. The passage of these stones can be very painful for the patient.^1,2

Causes and risk factors

AKU is a hereditary disease that is caused by a mutation in the homogentisate 1, 2-dioxygenase (HGD) gene. It is an autosomal recessive condition; this means that both parents must have the gene to pass it to their child. Each parent of the AKU patient has a copy of the HGD gene but they themselves do not display apparent signs or symptoms of the disease.²

Management of black bone disease

Currently, there is no treatment or cure for AKU. It is considered a lifelong condition and its management is aimed to treat the related symptoms.

The following methods of management can make the AKU patient feel better:

Nitisinone

Nitisinone is not licensed for the treatment of AKU. It is available "off label" at the National Alkaptonuria Center, which is based at Royal Liverpool University Hospital and treats all alkaptonuria patients.

According to his interview with Front Life Genomics, Nick Sireau (Chair and CEO of the AKU Society) talked about his journey to find a treatment for AKU to help patients with it, especially his two children who were diagnosed with AKU.

Due to his efforts in raising and securing the money for the clinical trial for the treatment of AKU, the European Commission approved nitisinone marketing authorisation in October 2020. This happened after a clinical trial showed a drop in circulating HGA and 

Diet

Limiting protein in the diet may be able to slow the progression of the illness if it is diagnosed in childhood. A low-protein diet can help adult AKU patients taking nitisinone by reducing its side effects. Patients should seek further advice from their doctor regarding this.^1-3 

Exercise

Gentle, regular exercise can help a patient with black bone disease a lot if they suffer from pain and stiffness in their bones and joints.

The AKU Society recommends that patients should avoid sports that impose additional strain on joints, such as boxing, football, and rugby, and instead try moderate exercises like yoga, swimming, and pilates. Asking your GP or physiotherapist for advice is a good choice.^1-3

Pain relief

AKU patients often receive anti-inflammatory drugs to treat their joint and bone symptoms. In severe cases, stronger drugs such as narcotics can be prescribed. It is always best to take advice from your GP on ways to manage the pain.^1,2

Emotional support

The experience of being diagnosed with AKU can be confusing and scary. As with any lifelong health condition, the patient may feel stressed about their treatment journey. Hence, emotional support from family and friends is very important.^2,3

Surgery

Sometimes surgery may be necessary if joints are damaged and need to be replaced or if heart valves or vessels have hardened.^1,2

Summary

Black bone disease, also known as Alkaptonuria (AKU) or black urine disease is a rare genetic metabolic disorder that prevents the body from completely breaking down two proteins called tyrosine and phenylalanine, resulting in the build-up of a chemical called homogentisic acid.

AKU is an autosomal recessive condition, making it quite rare. Currently, there is no treatment or cure for AKU, but the symptoms can be managed.