Classical Homocystinuria (CBS Deficiency)

Overview

• Classical Homocystinuria, also known as Cystathionine Beta-Synthase (CBS) Deficiency, is characterized by elevated levels of homocysteine in blood and urine.
• Amino Acids: Building blocks of proteins, essential for growth and development.
• Enzymes: Proteins that catalyze chemical reactions.

Biochemical Basis

• CBS deficiency occurs due to a malfunction in the enzyme that converts methionine to cysteine.
• Results in a buildup of methionine and homocysteine, with reduced cysteine production.

Symptoms

• Infants: Slow growth, weight gain issues, developmental delays.
• Post age 3:
  • Ocular Symptoms: Lens dislocation, cloudiness, severe nearsightedness, iris quivering.
  • Vision Issues: Damage to optic nerve, severe headache/eye pain, blurry vision, retinal damage.
  • Skeletal Abnormalities: Long limbs, inward bending knees, high foot arches, protruding or sunken chest.
  • Older Individuals: Decreased bone density, risk of fractures.
  • Blood Clots: Can lead to strokes (brain), pulmonary embolism (lungs).
  • Mental Health: Intellectual disability, anxiety, depression, OCD.

Genetic Cause

• Mutations in the CBS gene following autosomal recessive inheritance.
• Mutated CBS gene reduces cystathionine beta-synthase enzyme activity.
• Disrupts amino acid stability, affecting connective tissue and proteins.

Diagnosis

• Clinical Examination: Patient history, signs, symptoms assessment, and physical examination.
• Specialized Tests: Blood and urine tests for homocysteine, methionine, cysteine levels; genetic testing for CBS gene mutations.
• Newborn Screening: Elevated methionine levels detection.

Treatment

• Primary Treatment: Vitamin B6 supplementation (pyridoxine) to assist in converting homocysteine to cysteine.
• Betaine: For individuals unresponsive to B6, helps break down homocysteine.
• Dietary Changes: Low protein diet, limiting animal proteins, and increasing plant-based proteins.
• Metabolic Foods and Supplements: Special foods, and vitamins B9, B12, and cystine as needed.
• Other Symptoms: Treated as appropriate.

Genetic Counseling

• Helps families understand genetics, natural history, and provides psychosocial support.

Recap

• CBS deficiency results in high homocysteine levels, causing variable symptoms, mainly ocular and skeletal issues, and in severe forms, blood clots.
• Caused by CBS gene mutations, diagnosed with clinical and specialized tests.
• Treated with B6, betaine, and dietary adjustments.