Homocystinuria
Also known as: Classical Homocystinuria, HCU, CBS Deficiency, Cystathionine Beta-Synthase Deficiency
Homocystinuria is a rare, inherited metabolic disorder caused by a deficiency of cystathionine beta-synthase (CBS), an enzyme essential for processing methionine. This deficiency leads to an abnormal accumulation of homocysteine and its metabolites in the blood and urine, causing a range of systemic complications affecting the eyes, skeleton, brain, and vascular system.
Imagine your body has a special machine that helps break down food. In homocystinuria, one part of that machine is broken, causing a build-up of a substance called homocysteine. This can cause problems with your eyes, bones, brain, and blood. Doctors can help by giving you special vitamins and a special diet to keep you healthy.
Signs & Symptoms
- Dislocation of the lens of the eye (ectopia lentis)
- Myopia (nearsightedness)
- Increased risk of blood clots (thromboembolism)
- Developmental delay
- Intellectual disability
- Skeletal abnormalities (e.g., scoliosis, pectus excavatum/carinatum)
- Osteoporosis
- Seizures
- Psychiatric disorders
- Failure to thrive
Treatment Options
Vitamin B6 (Pyridoxine) Supplementation
MODERATELY EFFECTIVEBetaine (Trimethylglycine)
HIGHLY EFFECTIVEFolic Acid Supplementation
SUPPORTIVEVitamin B12 (Cobalamin) Supplementation
SUPPORTIVEDietary Methionine Restriction
HIGHLY EFFECTIVECystine Supplementation
SUPPORTIVEManagement of Thromboembolism
SUPPORTIVEOphthalmological Management (e.g., lens extraction)
SUPPORTIVEDiagnosis
- Newborn screening (measuring methionine levels)
- Plasma amino acid analysis (elevated homocysteine and methionine)
- Urine organic acid analysis (homocysteine metabolites)
- CBS enzyme activity assay in fibroblasts
- Genetic testing (CBS gene sequencing)
History
Homocystinuria was first described in 1962 by Gerritsen, Vaughn, and Waisman, who identified elevated levels of homocysteine in the urine of a patient with intellectual disability and dislocated lenses. The enzymatic defect, CBS deficiency, was subsequently identified, leading to a better understanding of the metabolic pathway and the development of targeted therapies.
Recent Breakthroughs
Advances in Newborn Screening for Homocystinuria
Improved tandem mass spectrometry techniques have enhanced the sensitivity and specificity of newborn screening programs, allowing for earlier detection and intervention in infants with homocystinuria.
Novel Therapeutic Approaches Targeting Homocysteine Metabolism
Research is ongoing to explore novel therapeutic strategies, including enzyme replacement therapy and gene therapy, to address the underlying metabolic defect in homocystinuria. Preclinical studies have shown promising results in animal models.