Homocystinuria is a rare but serious inherited metabolic disorder that affects how the body processes certain amino acids, particularly methionine. The condition results from genetic mutations that impair the breakdown of homocysteine, causing toxic levels to build up in the blood and urine. This biochemical imbalance can affect multiple systems, including the eyes, bones, brain, and blood vessels, and can lead to severe health complications if left untreated.
What Causes Homocystinuria?
Homocystinuria most commonly occurs due to a deficiency of the enzyme cystathionine beta-synthase (CBS). This enzyme is essential for converting homocysteine into other beneficial compounds. When CBS activity is reduced or absent, homocysteine accumulates and damages connective tissue and blood vessels. The condition follows an autosomal recessive inheritance pattern, meaning a child must inherit two faulty gene copies—one from each parent—to develop the disorder.
While CBS deficiency is the most frequent form, other rare variants involve methylation pathway defects or problems in vitamin B12 metabolism. Although these types differ in presentation and treatment, they all share the hallmark feature of elevated homocysteine levels.
Signs and Symptoms
Newborns with homocystinuria often appear healthy at birth, and early signs can be subtle or delayed. Symptoms usually develop during infancy or early childhood and may include developmental delays, learning difficulties, visual problems, and skeletal abnormalities. In some cases, the first sign is a severe event such as a stroke or blood clot, highlighting the importance of early screening.
Why Early Diagnosis Matters
Early detection dramatically improves outcomes. Treatment typically combines a low-methionine diet, vitamin B6 (pyridoxine) supplementation, and other targeted therapies to keep homocysteine levels under control. With strict adherence to treatment, many individuals lead healthy, active lives.
Because the disorder affects multiple systems, a multidisciplinary approach is essential. Patients often require care from specialists such as geneticists, dietitians, ophthalmologists, and cardiologists. Regular monitoring and lifelong compliance are key to preventing complications like vision loss, osteoporosis, and thromboembolic events.
Looking Ahead
Advances in newborn screening and research into gene-based therapies are improving the outlook for homocystinuria. However, lack of awareness and limited screening in some regions still lead to delayed diagnoses. Education and early intervention remain critical in reducing the long-term burden of this condition.
The following sections explore the condition in detail, starting with its underlying causes.
