History of PKU
Transcript of History of PKU
7/22/2019 History of PKU
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Celebrating 75 Years Since the Discovery of PKU
By Virginia Schuett, editor, National PKU News
Birmingham Children’s Hospital in England,
in collaboration with Dr. Horst Bickel using
an idea first proposed by the British Dr. Louis
Woolf in 1949. The reduced phe milk protein
is given to a child with PKU over a period of 6
months and shown to cause improvements in
mental development and behavior. This leads to
recognition that early treatment is crucial for the
best outcome.
1957 Maternal PKU is first identified as thesyndrome that results when women with high
blood phe levels have babies. The high en utero
phe levels cause mental retardation and a variety
of other problems.
1957 The “Wet Diaper” Test for PKU is
developed in Oregon by Dr. Willard Centerwall.
This test for excretion of high levels of phenyl-
pyruvic acid allows diagnosis of PKU, but it is
not accurate for some time after birth.
1958 Lofenalac (Mead
Johnson), a formula
made from hydrolyzedmilk protein to be low in
phenylalanine, is the first
commercially available
low phe formula for the
treatment of PKU to be
approved by the FDA in
the US.
1960 A filter paper screening test for PKU is
developed by Dr. Robert Guthrie in Buffalo, NY,
and becomes known as the Guthrie Test. This
inexpensive and accurate bacterial inhibition
test run on a small spot of blood makes mass
screening for PKU possible at birth, to prevent
its harmful effects.
1961 A field trial of newborn screening
for PKU is begun in the US on nearly one
million infants using the Guthrie Test and
demonstrates the feasibility of mass screening.
1962 Dr. Fölling receives the first Joseph
P. Kennedy International Award in Mental
Retardation from then-President John F.
Kennedy at the White House.
This year we celebrate the 75th anniversary of the
discovery of PKU, a small but important chapter
in the history of medicine. To commemorate
what was such a crucial discovery for all of us, I
wanted to outline other landmark events along
the way that have shaped PKU treatment and
thus for each of us in the PKU community have
shaped our own individual lives.
1934 PKU is discovered in Norway by Dr.
Asbjörn Fölling, one of Norway’s first physiciansto apply chemistry to medicine. He calls it
“imbecillitas phenylpyruvica”
because of the serious mental
retardation found in the first
two children identified with the
disorder, Liv and Dag Egeland
( pictured with their parents at
right ), and the phenylpyruvic
acid in the urine. Dr. Fölling
later finds that the abnormal
amounts of phenylpyruvic acid
in the urine of these children
is caused by their inability to
metabolize phenylalanine,
and suggests the autosomal
recessive genetic nature of the
disorder.
1935 The name imbecillitas
phenylpyruvica is changed to
phenylketonuria, as suggested
by Dr. Lionel Penrose, an eminent British
medical geneticist, because of the characteristic
appearance of the “phenylketone,” phenylpyruvic
acid, in the urine. He further defines the
chemical basis of the disorder in years to come.
1937 PKU is found to be caused by abnormal
functioning of the enzyme phenylalanine
hydroxylase by Dr. George Jervis, Director of
the Institute for Basic Research of the New
York State Office of Mental Retardation and
Developmental Disabilities.
1951 First diet treatment for PKU is developed
in the laboratory of Dr. Evelyn Hickmans at
1963 Mass screening of newbornsusing the Guthrie Test begins.
Dr. Guthrie travels the US to advocate for
newborn screening laws to be enacted.
1967 By this time, 37 states have mandatory
newborn screening laws for PKU. Led by
Richard Koch, Los Angeles, California, The
National Collaborative Study for the Treatmen
of PKU begins, involving 16 clinics and studyin
211 children over a period of 16 years; the studyultimately confirms the value of early treatmen
and low blood phe levels.
1983 The human phenylalanine hydroxylas
gene is isolated and cloned by Dr. Savio Woo
at Baylor College of Medicine in Texas, paving
the way for carrier identification and importa
PKU gene therapy research.
1984 Again led by Dr. Richard Koch, TheInternational Maternal PKU Study begins,
involving 91 clinics in the US, Canada and
Germany; it ultimately documents that levels of
6 mg/dl during pregnancy produce good result1990 A genetically altered mouse is engineer
to have PKU by Dr. David McDonald and Dr
Alexandra Shedlovsky at the University of
Wisconsin’s McArdle Laboratories in Madiso
This “PKU mouse model” gives researchers a
vital tool for carrying out experiments that ar
impossible or unethical in humans.
1993 National PKU Treatment Guidelines
and Standards are developed at a National
Institutes of Health Consensus Conference to
make PKU treatment more uniform in the U
“Treatment for Life” is emphasized.
2007 BioMarin’s Kuvan (sapropterin
dihydrochloride), a synthetic version of a
natural cofactor for the enzyme missing or
malfunctioning in PKU, is the first drug (a pi
approved by the FDA to lower blood phe leve
in some people with PKU.
2009 BioMarin clinical trials begin for
studying an enzyme replacement therapy for
PKU using pegylated phenylalanine ammoni
lyase (PEG-PAL) injections.
Liv (left), age 7, and Dag, age 4, the first children
diagnosed with PKU by Dr. Fölling, with their
parents, Dag and Borgny Egeland, Norway, 1934.
Dr. Asbjörn Fölling.
Volume 2NumberFall 200
News And Information About Phenylketonuria