Phenylketonuria-PKU
Newborn screening of phenylketonuria
in China (1982.5-1985.1)
? district No,screened No,of PKU incidence
? Beijing 45,609 3 1/15,200
? Tianjin,Hebei 30,396 4 1/7,600
? Shanhai,
East China 45,288 1 1/45,000
? East-north
China 51,288 4 1/6,800
? Sanxi,Sichuan 25,800 0 -
? total 198,320 12 1/16,500
Pathogenesis and
Clinical manifestations
Major metabolism of phenylanine and pathogenesis
of PKU
phenylalanine thyroxine
对羟苯丙
氨酸
尿黑酸
乙酰乙酸
CO2+H2O
多巴
去甲肾
上腺素
Adrenaline
Melanine
Phenylpyruvicacid
羟基苯
乙酸
苯乳酸 苯乙酸
二氢生物
喋呤还原酶
Phenylalaninehydroxylase
Tyrosine
四氢生
物喋呤
二氢生
物喋呤
酶缺陷
symptoms of
CNS
尿臭
FeCl3阳性 White skin
and brown
hair
Clinical manifestations of PKU,
whitish skin and brown hair
Clinical manifestations of
PKU,whitish skin and
brown hair
squamatous eczema
Skin lesion smear shows large amount
of Candida albicans
Adjunct
examinations
8-month old PKU patient with mild diffuse brain
function abnormal on EEG
Lab findings of PKU
? FeCl urine test:positive at 4～ 6months after
birth,with high false positive rate
? Guthrie test:for newborn screening
? Determination of serum phenylalanine (>6mg/dl)
? Phenylalanine tolerance test:for genetic carrier
detection(100mg/kg p.o.4-6 hours later determine
phanylalanine serum level )
? BH4 tolerance test,for differentiating various type of
PKU
Aminoacid analysis
equipment
Normal phenylalanine serum level
Normal phenylalanine serum level
High peak of serum phenylalanine
in PKU patient
Elevated phenylalanine serum level
Diagnosis and Newborn
Screening
（ 1） serum phenylalanine level > 1200?mol/l
（ 20mg/dl） of breast fed or regular bottle fed infants；
（ 2） Serum tyrosine level < 250 ?mol/l（ 5 mg/dl）
（ 3） BH4 deficiency has been excluded
Diagnostic criteria of PKU
Blood spots for Guthrie
screening test
Guthrie Newborn PKU screening
Schematic diagram of Guthrie
newborn screening test
Healthy child
There are no Bacillus
subtilis growth
culture
Agar mediumPut the blood
spot here
Schematic diagram of Guthrie
newborn screening test
Patient with PKU
There are no Bacillus
subtilis growth
culture
Agar mediumPut the bloodspot here
phenylananine embryopathy
? low birth weight
? psychomotor-retardation
? microcephaly
? congenital embryopathy
Therapy & Prevention
elevated serum
phenylalanine level
Serum Phe determination
under normal diet
elevated normal
serum
DHPR
False positive,no
need of follow-up
normal abnormal BH4
deficiency
Phe > 600?mol/l
(>10 mg/dl)
Phe360-600?mol/l
(>6-10 mg/dl)
Phe180-360?mol/l
(>3-6 mg/dl)
PKU Medium
MHP
Mild MHP
Diet control
Diet follow-up
Normal
diet and
follow-up
Tested once
again
<24hrs>4 mg/dl
>24hrs> 6 mg/dl
very possible will
be:
Algorithm of PKU
newborn screening
age serum level should be
maintained at
infants 120-360 ?mol/l（ 2-6 mg/dl）
school aged 480 ?mol/l (8 mg/dl)
adolescenct < 700 ?mol/l （ 12 mg/dl）
diet therapy is needed if,persistent >400
?mol/l（ 6.7mg/dl） 20 days after birth
Serum level of Phenylalanine > 1,200 ?mol/l（ 20
mg/dl） during pregnancy,95％ of their offsprings
will suffer from mental retardation
Serum phenylalanine level should be kept
at（ 120-360 ?mol/L or 6 mg/dl） during the
entire pregnancy
Recommendation
If pregnant woman’s MHP of non-PKU origin >400
?mol/l（ 6.7 mg/dl）,diet should be under control
during the entire gestational period
the following food should be avoided according
to the tolerance status of the patient
? Meat,fish and sausage
? eggs
? milk,yogurt,cheese,
? nut
? chocolate
? Milk containing icecream
? dairy product that contains asparagic acid
gene mutation of germ cells
pregnancy
environment protection,
quit bad habits
carrier detectionmarriage and bearing
instruction
prenatal diagnosis
newborn screening
Early diagnosis
Prevention of PKU
Impact of consanguineous
marriage
1/4 x 1/8 =1/32 1/4 x 1/50 = 1/200
PKU zygotes
1/8Cousinship 1/50 Non-consanguine
risk increase by 6.2 times
Newborn screening of phenylketonuria
in China (1982.5-1985.1)
? district No,screened No,of PKU incidence
? Beijing 45,609 3 1/15,200
? Tianjin,Hebei 30,396 4 1/7,600
? Shanhai,
East China 45,288 1 1/45,000
? East-north
China 51,288 4 1/6,800
? Sanxi,Sichuan 25,800 0 -
? total 198,320 12 1/16,500
Pathogenesis and
Clinical manifestations
Major metabolism of phenylanine and pathogenesis
of PKU
phenylalanine thyroxine
对羟苯丙
氨酸
尿黑酸
乙酰乙酸
CO2+H2O
多巴
去甲肾
上腺素
Adrenaline
Melanine
Phenylpyruvicacid
羟基苯
乙酸
苯乳酸 苯乙酸
二氢生物
喋呤还原酶
Phenylalaninehydroxylase
Tyrosine
四氢生
物喋呤
二氢生
物喋呤
酶缺陷
symptoms of
CNS
尿臭
FeCl3阳性 White skin
and brown
hair
Clinical manifestations of PKU,
whitish skin and brown hair
Clinical manifestations of
PKU,whitish skin and
brown hair
squamatous eczema
Skin lesion smear shows large amount
of Candida albicans
Adjunct
examinations
8-month old PKU patient with mild diffuse brain
function abnormal on EEG
Lab findings of PKU
? FeCl urine test:positive at 4～ 6months after
birth,with high false positive rate
? Guthrie test:for newborn screening
? Determination of serum phenylalanine (>6mg/dl)
? Phenylalanine tolerance test:for genetic carrier
detection(100mg/kg p.o.4-6 hours later determine
phanylalanine serum level )
? BH4 tolerance test,for differentiating various type of
PKU
Aminoacid analysis
equipment
Normal phenylalanine serum level
Normal phenylalanine serum level
High peak of serum phenylalanine
in PKU patient
Elevated phenylalanine serum level
Diagnosis and Newborn
Screening
（ 1） serum phenylalanine level > 1200?mol/l
（ 20mg/dl） of breast fed or regular bottle fed infants；
（ 2） Serum tyrosine level < 250 ?mol/l（ 5 mg/dl）
（ 3） BH4 deficiency has been excluded
Diagnostic criteria of PKU
Blood spots for Guthrie
screening test
Guthrie Newborn PKU screening
Schematic diagram of Guthrie
newborn screening test
Healthy child
There are no Bacillus
subtilis growth
culture
Agar mediumPut the blood
spot here
Schematic diagram of Guthrie
newborn screening test
Patient with PKU
There are no Bacillus
subtilis growth
culture
Agar mediumPut the bloodspot here
phenylananine embryopathy
? low birth weight
? psychomotor-retardation
? microcephaly
? congenital embryopathy
Therapy & Prevention
elevated serum
phenylalanine level
Serum Phe determination
under normal diet
elevated normal
serum
DHPR
False positive,no
need of follow-up
normal abnormal BH4
deficiency
Phe > 600?mol/l
(>10 mg/dl)
Phe360-600?mol/l
(>6-10 mg/dl)
Phe180-360?mol/l
(>3-6 mg/dl)
PKU Medium
MHP
Mild MHP
Diet control
Diet follow-up
Normal
diet and
follow-up
Tested once
again
<24hrs>4 mg/dl
>24hrs> 6 mg/dl
very possible will
be:
Algorithm of PKU
newborn screening
age serum level should be
maintained at
infants 120-360 ?mol/l（ 2-6 mg/dl）
school aged 480 ?mol/l (8 mg/dl)
adolescenct < 700 ?mol/l （ 12 mg/dl）
diet therapy is needed if,persistent >400
?mol/l（ 6.7mg/dl） 20 days after birth
Serum level of Phenylalanine > 1,200 ?mol/l（ 20
mg/dl） during pregnancy,95％ of their offsprings
will suffer from mental retardation
Serum phenylalanine level should be kept
at（ 120-360 ?mol/L or 6 mg/dl） during the
entire pregnancy
Recommendation
If pregnant woman’s MHP of non-PKU origin >400
?mol/l（ 6.7 mg/dl）,diet should be under control
during the entire gestational period
the following food should be avoided according
to the tolerance status of the patient
? Meat,fish and sausage
? eggs
? milk,yogurt,cheese,
? nut
? chocolate
? Milk containing icecream
? dairy product that contains asparagic acid
gene mutation of germ cells
pregnancy
environment protection,
quit bad habits
carrier detectionmarriage and bearing
instruction
prenatal diagnosis
newborn screening
Early diagnosis
Prevention of PKU
Impact of consanguineous
marriage
1/4 x 1/8 =1/32 1/4 x 1/50 = 1/200
PKU zygotes
1/8Cousinship 1/50 Non-consanguine
risk increase by 6.2 times
