Genetic Disorder: Single genetic disorder
Examples of Single genetic disorder: Phenylketonuria
Recommended Book: Human Genetics book
Resource material
Lee, Kimberly G., and David Zieve. "Phenylketonuria - PubMed Health." PubMed Health. A.D.A.M., Inc., 17
June 2011. Web. 12 Nov. 2011. <http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002150/>.
"PAH - Phenylalanine Hydroxylase - Genetics Home Reference." Genetics Home Reference - Your Guide to
Understanding Genetic Conditions. 7 Nov. 2011. Web. 12 Nov. 2011. <http://ghr.nlm.nih.gov/gene/PAH>.
Phenylketonuria:
Phenylketonuria (PKU) is an autosomal recessive metabolic genetic disorder characterized by a
mutation in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it
nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine (Pheala) to
the amino acid tyrosine.
When PAH activity is reduced, conversion of phe ala into tyrosine will not take place. In result
phenylalanine accumulates in the body and lead to hyperphenylalanemia .
This elevated concentration of phenylalanine then will join the alternative pathway and
ultimately converted into phenylpyruvate (also known as phenylketone), which is detected in the
urine.
History
Phenylketonuria was discovered by the Norwegian physician Ivar Asbjørn Følling in 1934. Dr.
Følling was one of the first physicians to apply detailed chemical analysis to the study of disease.
Therefore, in Norway, this disorder is known as Følling's disease, named after discoverer name. In
this disorder he observed hyperphenylalaninemia (HPA) was associated with mental retardation.
His careful analysis of the urine of two affected siblings led him to request many physicians near
Oslo to test the urine of other affected patients. This led to the discovery of the same substance he
had found in eight other patients. He conducted chemical analysis of urine which revealed the
presence of benzaldehyde and benzoic acid, which led him to conclude that the compound
contained a benzene ring. Further testing showed the melting point of the detected substance was
similar to phenylpyruvic acid, which indicated that the substance was in the urine.
painstaking research with other
disorders. It was recently suggested that PKU may resemble amyloid diseases, such as Alzheimer's
disease and Parkinson's disease, due to the formation of toxic amyloid-like assemblies of phenylalanine.
1935: Dr. Penrose, a British medical geneticist, renames “imbecillitas phenylpyruciva” to what we now
know as “Phenylketonuria”
1937: Dr. Jervis discovers PKU is caused by the malfunctioning of the enzyme PAH.
1951: Dr. Hickmans and Dr. Bickel develops the first diet treatment. This also made their discovery that
early treatment of PKU is crucial in their first steps to mental retardation
1957: Maternal PKU is identified. When women with high levels of phe in their blood gives birth to
babies with PKU symptoms
Dr. Centerwall develops the “Wet Diaper” Test where the excretion of phenylpyruvic acid allows
diagnosis of PKU in infants.
1958: Lofenalac, a formula made from hydrolyzed milk protein, is approved by the FDA to be low
in phe and a treatment for PKU.
1960: Dr. Guthrie develops the Guthrie Test, a filter paper screening test for PKU, which makes
detection of PKU possible at birth.
1967: 37 states have mandatory newborn screening laws for PKU.
1980s: mapping and cloning of PAH gene
1990s: PKU more than a simple Mendelian trait; also behaves as complex, Multifactorial disor
der
2000s: Non-dietary treatments for PKU developed
2007: Kuvan, a synthetic version of the missing PAH enzyme, is the first drug (pill) approved by the
FDA to lower blood phe levels in some people with PKU. Though it hasn’t been specified for
1958: Lofenalac, a formula made from hydrolyzed milk protein, is approved by the FDA to be low
in phe and a treatment for PKU.
1960: Dr. Guthrie develops the Guthrie Test, a filter paper screening test for PKU, which makes
detection of PKU possible at birth.
1967: 37 states have mandatory newborn screening laws for PKU.
1980s: mapping and cloning of PAH gene
1990s: PKU more than a simple Mendelian trait; also behaves as complex, Multifactorial disorder
2000s: Non-dietary treatments for PKU developed
2007: Kuvan, a synthetic version of the missing PAH enzyme, is the first drug (pill) approved by the
FDA to lower blood phe levels in some people with PKU. Though it hasn’t been specified for