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17 Cards in this Set
- Front
- Back
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Cross reactive material |
Protein produced by mutant gene that reacts with antibody for wild type protein. CRM+ - enzyme present, activity deficient CRM- - enzyme not present, no activity |
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Biochemical heterogeneity |
Same pathway, different metabolites accumulated |
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Molecular heterogeneity |
Same gene, different mutations |
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Amino acid analysis |
1. Separate amino acids by chromatography in amino acid analyzer based on dissociation constant and charge. 2. Stain with ninhydrin at 100 degrees to form Ruhemanns Purple. Absorbance at 570 nm relates to concentration. |
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Causes of hyperammonemia |
Liver disease Transient hyperammonemia of newborn (immaturity) Reye syndrome - diagnosis of exclusion Poisonings Inborn errors of metabolism |
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Uric Acid Cycle |
Ornithine + Carbamoyl Phosphate -CPSI-> Citrulline Citrulline + Aspartate -AS-> Arginosuccinate Arginosuccinate -AL-> Fumarate + Arginine Arginine -Arginase-> Urea + Ornithine Carbamoyl phosphate is also used to create orotate (pyrimidine biosynthesis) |
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CPSI Deficiency |
AR. Increased glutamine, decreased citrulline, no orotic acid. |
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OTC deficiency |
XLR. Increased ornithine and glutamine, decreased citrulline and arginine. Ammonia intoxication in males, variable phenotype in females (protein avoidance) Manage with protein restriction, nitrogen scavengers (benzoate/phenylbutyrate), liver transplant. |
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Citrullinemia (AS deficiency) |
AR. Increased citrulline. |
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AL deficiency |
AR. Increased arginosuccinate and citrulline. |
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Ammonia scavenging medications |
Benzoate -> Benzoyl coA Benzoyl coA + Glycine -> Hippurate
Phenylbutyryl -> Phenylbutyryl coA Phenylbutyryl coA + Glutamine -> Phenylacetylglutamine |
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Phenylalanine metabolism |
Diet -> Phe -phe hydroxylase-> Tyrosine -> Pigment, neurotransmitter, thyroxine Phenylalanine hydroxylase converts BH4, which is converted back by dihydropterin reductase. |
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Classic PKU |
Deficiency in pheylalanine hydroxylase (BH4) Classic form is AR. Intellectual disability, unusual stance, autistic like behaviors. Mousy odor from phenylketones. Light pigmentations, eczema. Confirm by plasma amino acids, DNA, urine biopterins. Restrict phenylalanine and dietary proteins. Treat with biopterins (sapropterin, kuvan) - synthetic BH4. 25-50% respond. |
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BH4 Synthesis |
GTP -> Dihydroneopterin triphosphate Dihydroneopterin Triphosphate -> PTP PTP -PTP reductase-> LTH PTP -sepipapterin reductase-> Sepiapterin LTH/Septiapterin -sepiapterin reductase-> Tetrahydrobiopterin |
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BH4 Defects |
Replenish neurotransmitters. Effects three hydroxylases. Phe -Phe hydroxylase-> Tyrosine -> Pigment, neurotransmitters, thyroxine Tyr -Tyr hydroxylase-> Dopamine, NE, E Trp -Trp hydroxylase-> Serotonin |
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Classes of HyperPhe |
1. Severe, Phe>1200 2. Persistent, >600 3. Mild, Phe<600 4. Transient, maturational defect 5. Cofactor defects |
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Maternal PKU Syndrome |
Caused by uncontrolled maternal Phe - acts as dose and time-dependent teratogen Developmental delay, microcephaly, congenital heart defect Fetal exposure is 2x concentration in mother's blood Goal is Phe < 6 mg 3 months before conception. |
