• autosomal recessive
• black urine disease (toxic alkapton accumulates and breaks down tissue in contact with urine)

• limit amount of substrate
• block the production of the abnormal protein or convert it into a non-pathological chemical
• Salvage an improperly folded protein and reactivate it to reinitiate the initial function

• Most common disease to affect aa synthesis
• Autosomal Rec
• 1/15000
• mental retardation, decreased pigmentation, etc
• caused by deactivation in phenylalanine hydroxylase enzyme which converts phenylalanine to tyrosine

• Undetectable at birth
• Major health problem
• Treatment is available
• Cost effective (compaired to later treatments)
• Reliable methods

• Specificity - 95% - 95 normals and 5 false positives
• Sensitives - 95% - 95 normals and 5 false negatives
• Want to increase specificity because this disease is treatable and you don't want to miss one

Guthrie Bacterial Inhibition Assay

• Blood is removed from patient and placed on filter paper disc
• Disc is placed in agar gel with bacteria and antibiotic to inhibit natural growth
• Presence of high levels of phenylalanine allows bacteria to grow
• Growth is proportional to levels of phenylalanine
• Since phenylalanine accumulates with time, blood must be taken at least 1 week after birth to allow for such accumulation

• allow for viewing of a large range of genetic diseases with one test

• Body requires both phenylalanine hydroxlylase and the BH₄ cofactor to convert it into tyrosine
• Any mutations in BH₄ may also cause PKU symptoms/phenotype

• Inability to break down galactose
• autosomal recessive
• 1:60000
• non-essential amino acid may be completely removed from the diet --> must completely remove milk and milk-products from the childs diet
• During devt, child shows progressively worse symptoms
• Total removal from diet does not ensure complete lack of galactose (still present naturally in body)
• chrome 9

• Autosomal recessive
• Lipid storage disorder (lysosomal storage disorder)
• 1:100000 in normal population
• 1:4000 in Ashkenazi Jew population
• Normal at birth, progressive symptomatic onset
• Symptoms --> seizures, paralysis, blindness, twitching
• large buildup of lipid within the cells
• hexosamidase A fails to breakdown proteins which results in a large complex which only affects the brain (G_M2 Ganglioside)

Sandhoff Disease

(milder Tay-Sachs)

• results when α- and β- hex A cannot break down the lipids and proteins

• Must be clinically significant disorder with no effective treatment --> little ability to improve life of the affected child
• High risk population
• Genetic counseling available and essential educational component
• Accurate/inexpensive tests
• Alternative reproduction options available

• defect in purine/pyrimidine metabolism
• Hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT)
• X-linked
• 1:400000
• Mental retardation, spasticity, arthritis, self-mutilation
• milder form exists
• progressive symptoms
• normal function allows for recycling of aa, but disease cannot recycle so must make every aa from scratch --> leads to high uric acid levels
• no treatment
• high mutation rate