phenylketonuria
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Transcript of phenylketonuria
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Hyperphenylalanin
aemia
Sarah M. Alfaqaih ,MDMBBS , ABClinical fellowship KHMC ( Royal medical services ) of inherited metabolic disorder
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Content: Introduction Metabolic derangement Clinical presentation Diagnosis workup Treatment Prognosis
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Defect in either PAH or the production or recycling of BH4 may cause hyper-PAH .
Autosomal recessive defect The PAH gene located on long arm
chromosome 12 No single prevalent mutation
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The prevalence varies between different population :
1 in million in Finland 1 in 2400 in Turkey
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Introduction Metabolic derangement Clinical presentation Diagnosis workup Treatment Prognosis
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Pathogenesis of brain damage of PKU is not fully understood
Tyrosine becomes semi-essential amino acid , with reduced blood levels leading to impaired synthesis of melanine , dopamine and norephinephrine
Increased blood level of PHA results in an imbalance of other large neutral amino acid within the brain ( decrease TYR , serotonin )
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Introduction Metabolic derangement Clinical presentation Diagnosis workup Treatment Prognosis
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Mousy odour ( phenylacetic acid ) Eczema 20-40% Sever mental retardation IQ<= 50 Reduced hair , skin and iris
pigmentation Reduced growth and microcephaly
and neurological impairments: 25% epilepsy , 30% tremor , 5% spasticiy of limbs , 80% EEG abnormalities
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The face of this patient with PKU illustrates the rather subtle eczematoid rash. The brown eyes remind us that all patients with this disease do not have blue eyes. In addition, he had epicanthal folds and a left internal strabismus
Fig:1(2)
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Severely retarded, institutionalized brothers with untreated PKU. They were quite fair of hair
and skin.Fig:2(2)
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Almost all untreated patients show behavioral problems , which include hyperactivity , purposeless movements , aggressiveness , anxiety and social withdrawal .
The clinical phenotype correlate with PHE blood level .
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Introduction Metabolic derangement Clinical presentation Diagnosis workup Treatment Prognosis
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PKU is detected by neonatal secrening ( Guthrie , enzymatic techniques , tandum mass spectrometry ).
PHE level that is taken as a positive result requiring further investigation (120-240µmol\l , also PHE\TYR ratio >3 used in some labs ).
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A positive ferric chloride test in a patient with untreated
PKU.Fig:3 (2)
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Introduction Metabolic derangement Clinical presentation Diagnosis workup Treatment Prognosis
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Principle of treatment Dietary treatment
PHE free amino acid formula .Breast milk has a relatively low amount of PHE.Meat , fish , milk , yogurt ,cream , egg , rice and cheese contains a higher concentration of PHE.
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(2)
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(2)
9
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Treatment with BH4BH4 can reduce level of PHE in some patient with PKU BH4 responsiveness is determined by reduction of >= 30% in blood PHE level after a single dose of 10mg\kg body weight
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Monitoring of treatment(1)
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Alternative treatment Gene therapy : the development of
a safe and more successful gene transfere vector is still required before clinical trial in humans
Liver transplantation : the risk of transplantation surgery and post-transplantation immune suppressive medication are too high for it to be a realistic alternative .
Phenylalanine ammonia lyase
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Introduction Metabolic derangement Clinical presentation Diagnosis workup Treatment Prognosis
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The outcome is expected to be very good if the diet is closely followed, starting shortly after the child's birth. If treatment is delayed or the condition remains untreated, brain damage will occur. School functioning may be mildly impaired.
If proteins containing phenylalanine are not avoided, PKU can lead to intellectual disability by the end of the first year of life.
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Reference
1)Jean-Marie Saudubray ,Georges van den Berghe , John H. Walter (Editors) Inborn Metabolic Disease Diagnosis and Treatment, Fifth Edition2)William L. Nyhan , Bruce A. Barsho , Pinar T. Ozand, Atlas of Metabolic Diseases Second edition
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THANKS FOR ATTENSION