Homocystinuria By Erin Kammerer

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.

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

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

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)

Trans-Sulfuration Pathway

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

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

Treatments- Median IQ- Non B6 Responsive- 56 High doses of vitamin B6 -receive 25-100mg 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

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

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

References http://www.healthline.com/health/homocystinuria?toptoctest=expand http://ghr.nlm.nih.gov/condition=homocystinuria http://emedicine.medscape.com/article/1952251-overview http://www.nlm.nih.gov/medlineplus/ency/article/001199.htm http://livewell.jillianmichaels.com/cysteine-foods-4874.html http://go.galegroup.com/ps/i.do?id=GALE%7CA336826189&v=2.1&u=nysl_ca_sagecoll&it=r&p=AONE&sw=w&asid=350c5a8179e45e576b46f7bf44d1a699