Explain the Following Disorders of Amino Acid Metabolism: Homocystinuria and Hartnup Disease
a) Homocystinuria
Homocystinuria is an inherited disorder caused by a deficiency in the enzyme cystathionine beta-synthase (CBS), which leads to the accumulation of homocysteine and methionine in the blood and urine. This disorder is typically inherited in an autosomal recessive pattern.
Causes and Biochemistry
- Deficiency of CBS, which impairs the conversion of homocysteine to cystathionine
- Alternatively, defects in remethylation of homocysteine to methionine
Symptoms
- Developmental delays and intellectual disability
- Lens dislocation (ectopia lentis)
- Skeletal abnormalities similar to Marfan syndrome
- Osteoporosis and long, thin limbs
- Increased risk of thromboembolism
Treatment
- Diet low in methionine
- Supplementation with vitamin B6, B12, folic acid, and betaine
- Monitoring of homocysteine levels
b) Hartnup Disease
Hartnup disease is a metabolic disorder affecting the transport of neutral amino acids, especially tryptophan, in the kidneys and intestines. It is also inherited in an autosomal recessive manner.
Causes
- Mutation in the SLC6A19 gene, which encodes a transporter protein for neutral amino acids
- Impaired absorption and reabsorption of amino acids, leading to their loss in urine
Symptoms
- Pellagra-like skin rashes
- Intermittent episodes of cerebellar ataxia
- Emotional instability, depression, or psychosis
- Photosensitivity
Treatment
- High-protein diet
- Nicotinamide supplementation
- Avoidance of sun exposure
Both disorders underline the significance of amino acid metabolism in neurological and systemic health.