1. Homocystinuria
By Erin Kammerer

2. What is Homocystinuria?
Methionine metabolism disorder
Leads to an abnormal accumulation of homocysteine and its metabolites in the blood and urine
Affects 1 in 200,000 people world wide
Normally homocysteine is not found in appreciable quantities in blood or urine
More common in Ireland, Germany, Norway and Qatar.

3. Genetic defect-
Autosomal recessive defect in production of the enzyme cystathionine B-synthase (CBS)
Unable to produce amino acid cysteine
Becomes an essential amino acid
a key enzyme in trans-sulfuration pathway that converts homocysteine into cystathionine and then Cysteine
Cysteine

4. Chemical Structures- Methionine Homocysteine Cystathionine
The key molecules in the transsulfuration process and homocystinuria
Cystathionine

5. Enzymes and Cofactors-
Cystathionine B-Synthase
Important enzyme- Cystathionine B-Synthase
Cofactors for reaction from homocysteine to cystathionine with this enzyme- B6 and serine
Serine
Vitamin B6 (Pyridoxine)

6. Trans-Sulfuration Pathway

7. Symptoms- Early symptoms- Later symptoms-
Newborn infants appear healthy
Early symptoms-
Mildly delayed development
Increasing visual problems
Chest deformities
Psychomotor retardation
Later symptoms-
Ectopia lentis
‘Tight’ joints
Unusual susceptibility to bleeding
Long arms, legs and fingers
High arched foot
Demyelination and degeneration of white matter (learning disabilities)
Scoliosis

8. Diagnosis Conduct a series of tests- X-ray for signs of osteoporosis
Scoliosis test
Amino acid screen of blood and urine to check for excess homocysteine
Genetic testing
Skin Biopsy
Genetic testing to see if the genes involved in the disorders are present
-in a healthy person, there are no appreciable amounts of homocsteine in the blood or urine

9. Treatments- Median IQ- Non B6 Responsive- 56
High doses of vitamin B6
-receive mg daily
~1/2 of patients are responsive
25% of non B6 responsive individuals sustain a major vascular injury during childhood
~1/2 of non B6 responsive individuals will sustain ectopia lentis
by 5-10 years old
Median IQ-
B6 Responsive- 78
Non B6 Responsive- 56
No cure for homocystinuria
reduces homocysteine and methionine levels in the blood
if responsive, taken daily for life
25% of Non B6 Responsive individuals sustain a major vascular injury during childhood
-due to the unusual susceptability to bleeding
ectopia lentis- displacement of the lense in the eye

10. Daily Nutrition Recommendations-
1) Methionine restricted diet
-no eggs, fish, nuts/seeds, leafy greens
2)Betaine
-nutrient that works to remove homocysteine from the blood, converts back to Methionine
3)Taking a folic acid supplement and adding cysteine to the diet are helpful
postitive results from methionine restricted diet

11. Current Research Treatment with proteasome inhibitors in mice
Increased active Cystathionine B-Synthase activity
Decreased levels of homocysteine in the blood to a normal range
Response rates in the mice varied, may be useful for treatment but still needs testing

12. References