Homocystinuria By Erin Kammerer What is Homocystinuria Methionine

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

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 Cysteine

Chemical Structures- Methionine Homocysteine Cystathionine

Enzymes and Cofactors- Cystathionine B-Synthase Vitamin B 6 (Pyridoxine) Serine

Trans-Sulfuration Pathway

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

Treatments • High doses of vitamin B 6 -receive 25 -100 mg daily ~1/2 of patients are responsive • 25% of non B 6 responsive individuals sustain a major vascular injury during childhood • ~1/2 of non B 6 responsive individuals will sustain ectopia lentis by 5 -10 years old Median IQB 6 Responsive- 78 Non B 6 Responsive- 56

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

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%7 CA 336826189&v=2. 1&u=nysl_ca_s agecoll&it=r&p=AONE&sw=w&asid=350 c 5 a 8179 e 45 e 576 b 46 f 7 bf 44 d 1 a 699