in the name of godgdrc-cong.tums.ac.ir/images/slide/1.alaei-pku.pdf · the rapid differentiation...
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In the name of GOD
Phenylketonuria
Dr.mohammad raza alaei
Pediatric Endocrinologist
Shahid beheshty university
pathophysiology
Organic Acidemia
Diagnosis
Screening test
HPLC (phenylalanine & tyrosine)
Serum ph >360 micromol/l (> 6 mg/dl)
Phenylketones (Phenylpyruvate & phenylacetate)
PKU Classification
• Severe : >20
• Mild : 10 - 20
• Hyperphenylamia : 2 - 10
• Non classical : ( BH4 def)
CLINICAL MANIFESTATION
• Vomiting
• Delayed development(apparent in 4-9 month)
• MR(IQ<50),microcephaly,tremor,increa
sed muscle tone,parkinsonian-like
extrapyramydal symptoms
• Seizures(before 18 months)
• Blond,blue eye,rough skin,eczema
• Hyperactivity,autism
PKU mothers
• Spontaneous abortion
• PA level >20mg/dl :fetal brain
damage(MR,microcephaly),unusual
facies : upturned nose ,underdeveloped
philtrum,thin upper lip
• CHD,growth retardation
• Hypoplasia & partial agenesis of corpus calosum
Treatment
low-phenylalanine diet is initiated in the neonatal period
Mental retardation is prevented
breast-feeding is possible and should be encouraged
it can be used in conjunction with the special phenylketonuria formulas
Provide appropriate calories, nutrients, and protein for sustained normal growth
Treatment
phenylalanine is an essential amino acid.
detrimental effects on growth and development
may occur if restriction of phenylalanine intake is too
Severe.
maintain levels between 120 and 360 micM in children
younger than 12 years and between 120 and 600 micMin individuals older than 12 years.
most centers recommend lifelong treatment.
Initial Dietary Therapy for Classic PKU
Plasma phenylalanine
mg/dl
4-10
10-20
20-40
>40
Delete phenylalanine for
Hours
24
48
72
96
guidelines for initial dietary phenylalanine
Plasma phenylalanine
mg/dl
<10
10-20
20-30
30-40
>40
Distary phenylalanine
mg/kg
70
55
45
35
25
Non classical pku
Non classical pku : two percent of the
patients
every patient should be tested for an
abnormality of BH4
management and counseling are so
different
deteriorate neurologically despite
adequate control of plasma
phenylalanine
Non classical pku
Biopterine & neopterine
BH4 loading test
Analysis of pterins, folates, and
Neurotransmitterin in CSF
Enzyme assay
DHPR
BH4 Loading test
20 mg/kg body weight about 30 min before a regular meal
Blood samples should be collected at times 0, 4, 8, and 24 hours after BH4 administration
BH4 loading test is useful diagnostic test for the rapid differentiation between classic PKU and BH4 variants
Non classical pku
Non classical pku
• Present in three way:
• Asymptomatic ,found following
screening,& investigated for biopterin
defect
• Symptomatic despite a low – phe diet
• Symptomatic on a normal diet
Clinical presentation
Clinical presentation
Clinical presentation
Symptoms :
May be subtle in the newborn
Usually start after several months of
age
LBW in PTPS
Cerebral calcification in DHPR
Symptoms are mild & transient in PCD
Treatment
Treatment
• Special Diet
• BH4
• Neurotranimetter precursors
• Folinic acid
• Phenylalanine ammonia lyase
• Large neutral amino acid
• Gene therapy
Summary
• Compared with classical pku , BH4 def
is :
• More severe
• Treatment is more difficult
• Outcome is quite variable