in the name of godgdrc-cong.tums.ac.ir/images/slide/1.alaei-pku.pdf · the rapid differentiation...

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