Homocystinuria (HCU) overview
Causes & genetic inheritance of Homocystinuria (HCU)
Symptoms of Homocystinuria (HCU)
HCU dietary management and treatment
Living with HCU
Homocystinuria (HCU) overview
What is Homocystinuria (HCU)?
Homocystinuria, also known as HCU, is a rare inherited disorder of protein metabolism. This metabolic disorder affects the body's ability to metabolise and break down an amino acid found in protein: methionine. If methionine is not processed correctly by the liver, the by-products of the malfunctioning protein breakdown process, specifically homocysteine, accumulate to toxic levels in the body. Left untreated, high quantities of methionine and harmful by-products like homocysteine can damage the eyes, blood vessels, bones, and the brain.
While there is no cure for HCU, the disorder can be effectively managed with medication and a low-protein diet to control the intake of natural dietary protein. Lifelong adherence to a low-protein diet, supported by protein substitutes, ensures the body still receives sufficient protein, methionine, energy, vitamins, and minerals for growth and normal body function, enabling a better quality of life for people with HCU. People diagnosed with HCU will need regular blood tests and physical assessments to ensure their treatment is continually adapted according to age and metabolic needs.
Causes & genetic inheritance of Homocystinuria (HCU)
Homocystinuria is an inherited disorder passed from parents to their children. It is an autosomal recessive condition, meaning a child will have HCU if they inherit a defective gene from both parents. While the parents themselves may be healthy, they each carry a faulty gene affecting amino acid metabolism.
If both parents are carriers of this genetic anomaly, that affects the enzyme, which degrades homocysteine and methionine, there is a 25% chance with each pregnancy that their child will have HCU. However, because the gene change is uncommon, the overall chance of a child being born with HCU is low.
HCU also known as classical homocystinuria, caused by a deficiency in the cystathionine beta-synthase (CBS) enzyme. Might be present as pyridoxine responsive and non-responsive form. Another condition leading to elevated homocysteine in the blood is called MTHFR deficiency.
Symptoms of Homocystinuria (HCU)
Affected children with HCU are usually asymptomatic between ages 1-2. Symptoms typically appear from age 3 but may vary between individuals. Without dietary management, the symptoms of HCU can be severe and affect multiple systems.
Common symptoms of HCU include:
- Eye damage, such as myopia and dislocated lenses (ectopia lentis).
- Vascular damage (blood vessels), which can lead to blood vessel occlusions (thromboembolism) and cardiovascular risks.
- Bone damage and skeletal abnormalities.
- Learning and intellectual impairment.
- Neurological impairment (brain damage).
The disorder initially affects the eyes, followed by the bones, and may also impact mental development. Recognising early symptoms and ensuring early detection through newborn screening is crucial to mitigate these potential complications.
HCU dietary management and treatment
Managing HCU requires lifelong adherence to a low-protein diet supported by regular medical check-ups.
The role of Food for Special Medical Purposes and protein substitutes
Adherence to a lifelong low-protein diet is crucial for people with HCU. This diet is specifically designed to limit methionine intake, which helps keep blood methionine levels low and prevents homocysteine from building up to harmful levels. The diet mainly consists of low-protein foods supplemented with protein substitutes and other supplements as prescribed by a specialist healthcare professional. These methionine-free protein substitutes ensure the body still receives adequate protein, energy, vitamins, and minerals for growth and normal body function without providing additional methionine. Accuracy and consistency in following the diet are vital for healthy development.
Medical intervention
Beyond dietary management, Vitamin B6-nonresponsive form of HCU treatment often includes specific supplements. These can include betaine anhydrous, folic acid, and Vitamin B12.
Betaine anhydrous helps convert homocysteine back to methionine, reducing toxic levels. The effectiveness of treatment can vary depending on the type of HCU and individual response to these medications.
HCU diet and foods to avoid
A low-methionine, protein-restricted diet is essential for managing HCU. This involves carefully selecting foods low in methionine and avoiding foods high in methionine. Foods high in methionine to avoid generally include high-protein items such as:
- Meat and poultry
- Fish and seafood
- Dairy products (milk, cheese, yogurt)
- Eggs
- Legumes and beans
- Nuts and seeds
Specialised medical formulas are important to meet overall nutritional needs while limiting methionine intake.
Living with HCU
Living with HCU requires constant vigilance and commitment to a low-protein diet supported by regular medical check-ups. Ongoing support from a dietician specialising in metabolic disorders is essential to help manage the low-protein diet and ensure the correct amount of protein substitute and any other supplements are prescribed to meet protein requirements.
HCU presents different challenges throughout life. As a baby, child, teenager, and adult, the needs and experiences of a person diagnosed with HCU will vary. For example, babies need a special infant feed, in addition to breast milk and/or standard infant formula; children must learn to cope with dietary restrictions; teenagers may face social pressure; and adults must manage their diet while living an independent, busy lifestyle.
Regular check-ups with a doctor and/or dietitian are crucial to ensure ongoing effective management of the disorder as the body's needs change over time. By following a
low-protein diet and adhering to medical protocols, people with HCU can live healthy and full lives. For inspiration, delicious low-protein recipes are available.
