Lab Profiles UPDATED Choose from the below list. Australia Japan India Philippines ---US States------ Alabama Alaska Arizona Arkansas California Colorado Connecticut Delaware Florida Georgia Hawaii Idaho Illinois Indiana Iowa Kansas Kentucky Lousiana Maine Maryland Massachusetts Michigan Minnesota Mississippi Missouri Montana Nebraska Nevada New Hampshire New Jersey New Mexico New York North Carolina North Dakota Ohio Oklahoma Oregon Pennsylvania Rhode Island South Carolina South Dakota Tennessee Texas Utah Vermont Virginia Washington D.C. Washington State West Virginia Wisconsin Wyoming Public Health News Homocystinuria   Condition: Homocystinuria "Homocystinuria is caused when a baby is unable to use the amino acid methionine found in proteins of foods. This disorder can lead to mental retardation, seizures and usually death. A special low-protein diet helps to avoid many of these problems." - Vermont Newborn Screening More technical information from the Mountain States Genetic Network: Homocystinuria refers to elevated excretion of the amino acid homocystine. There are a number of causes, but the newborn screening test is designed to detect the inborn error cystathionine ß synthetase deficiency, which also causes elevated blood levels of methionine. This is an autosomal recessive inherited disorder of methionine metabolism, with an incidence rate of 1:80-100,000 newborns. Metabolic Pathway: HCU About 1:5,000 infants is found to have elevated blood methionine on newborn testing. In most cases this is a benign, temporary abnormality due to immature enzyme levels or a high protein intake. In the case of cystathionine ß synthetase deficiency, the infant is unable to transfer the sulfur atom of homocystine to cystine. Cystathionine ß synthetase deficiency is heterogeneous. About 40% of affected individuals respond to treatment with pyridoxine (vitamin B6) by normalization of methionine and homocystine levels, however, these infants usually have a small amount of residual enzyme activity and are often missed by newborn screening for methionine. B6-responsive patients have been detected by urine screening at one month of age in some programs. Clinical Features Homocystine levels of up to 0.2 µ mol/mL and methionine levels of up to 2 µ mol/mL characterize cystathionine synthetase deficiency. There are no symptoms in the newborn period; dislocated ocular lenses may occur in childhood, as well as thromboembolic events leading to stroke or premature death. Other signs and symptoms include intellectual impairment, seizures, arachnodactyly, joint stiffness, osteoporosis, fair skin and hair, liver damage, connective tissue damage, and psychiatric or emotional disorders. There is some evidence that heterozygotes (carriers) may be at increased risk for arteriosclerotic cardiovascular disease. Clinical diagnosis of homocystinuria rarely occurs before serious symptoms (dislocated lenses, retardation, or stroke) occur. Treatment is of variable efficacy. Besides classic homocystinuria, several forms of hypermethioninemia are known. The condition may be benign or occur in association with mental retardation and myopathy. Liver disease (hepatocellular damage) from hepatitis or tyrosinemia type I frequently causes elevations of serum methionine. Deficiency of folic acid or vitamin B12 causes methylmalonic acidemia with homocystinuria and metabolic disorders of B12 formation produce the same biochemical sequelae but different symptoms. Laboratory Tests A bacterial inhibition assay for methionine is used for screening. Normal methionine is less than < 1 mg/dL (30 µ M). Confirmatory testing requires a quantitative blood methionine level and, if elevated, diagnostic testing for homocystinuria. Liver function tests are needed and a urine for succinylacetone may also be necessary to exclude tyrosinemia. Treatment About 40% of individuals with cystathionine synthetase deficiency respond promptly to a high dose of vitamin B6 (pyridoxine 250-500 mgm daily). For the remainder, a diet restricted in methionine is needed. Compliance with the diet is difficult. A special medical food is required to provide other amino acids, vitamins, and minerals. Regular dietary monitoring is necessary, and biochemical response can be expected. Long-term outcome of patients treated by dietary restriction is not yet known. Antiplatelet agents such as aspirin or dipyrimazole may help prevent thromboembolic events. Screening Practice Considerations A positive screening test depends upon protein ingestion. Specimens obtained before 48 hours of age should be repeated. Prompt confirmatory testing is required even if there is evidence to suggest that one of the situations associated with false positive screens is present (these include early specimen collection, prematurity, heat-damaged specimen, hyperalimentation, or antibiotic therapy). The presence of any of these does not exclude the possibility of disease. The purpose of newborn screening is to identify infants at risk and in need of more definitive testing. As with any laboratory test, both false negative and false positive results are possible. Screening test results are insufficient information on which to base diagnoses or treatment.