phenylketonuria kuliah
TRANSCRIPT
Synonyms • PKU, • phenylalanine hydroxylase,• PAH, phenylalanine,• Phenylpyruvic acid, • Phenylacetic acid, • Hyperphenylalaninemia type I, • Folling's disease, • Phenylpyruvic oligophrenia
Background• Phenylketonuria (PKU) is the most
common inborn error of amino acid metabolism.
• Deficiency of the enzyme phenylalanine hydroxylase (PAH) :
• accumulation of phenylalanine in the plasma (>1200 mmol/L;
• excretion of phenylpyruvic acid and phenylacetic acid in the urine.
• Phenylalanine has ketogenic and gluconeogenic intermediates– Contribute to the glucose pool– Play a role in normal brain
development and function.• PKU is detected by screening
newborns. • Patients treated with a diet low in
phenylalanine can lead a normal life.
Pathophysiology:• The classic type of PKU is caused by a deficiency of PAH, resulting
in increased levels of phenylalanine in body fluids.
• PAH catalyzes the conversion of L-phenylalanine to L-tyrosine,
• Other types of PKU include PKU caused by impaired synthesis of BH4, GTP-CH I, 6-pyruvoyl tetrhydropterin (6-PTS), or dihydropteridine reductase (DHPR).
• Patients with the BH4 cofactor deficiency have more severe neurologic problems that are not completely corrected by the dietary reduction of phenylalanine.
• The learning disabilities in patients with PKU who are adequately treated may result from reduced production of neurotransmitters as a result of deficient tyrosine transport across the neuronal cell membranes.
Frequency• In the US: The incidence of classic PKU is
approximately 1 case per 15,000 births.
• Internationally: 4 cases per 100,000 individuals incidence is 350 cases per
million live births.
• Approximately 0.04-1% of the residents in mental retardation clinics are affected by PKU.
• Mortality/Morbidity: • Patients with PKU who are not treated have severe
mental retardation.
• Psychologic problems, agoraphobia• Race: PKU is common in whites and Asians and is
rare in blacks.
• Sex: No sexual predilection exists for PKU. Untreated maternal PKU increases the risk for developmental problems in offspring.
• Age: PKU can commonly be recognized in newborns with the help of newborn-screening programs.
CLINICAL FEATURE•
History:- Most patients appear healthy at birth.- In adult patients who stop dietary treatment, neurologic
dysfunction may occur.•
Physical: • Skin
Fair skin and hair impairment of melanin synthesis
Eczema (including atopic dermatitis)Light sensitivityPyogenic infections keratosis pilarisDecreased number of pigmented neviSclerodermalike plaques
•Other manifestations-Mental retardation-Musty odor-Epilepsy (50%)-Extrapyramidal manifestations, such as parkinsonism-Eye abnormalities, such as hypopigmentation
CAUSES
•PKU is an autosomal recessive disorder caused by mutations at the PAH locus on bands
12q22-24.1.
• Other causes of PKU include BH4 and DHPR deficiency.
DIFRENSIAL DIAGNOSIS
• Hyperphenylalaninemia• Tetrahydrobiopterin deficiency• Tyrosinemia• Liver disease• Other diseases with mental retardation• Tyrosinemia type II (Richner-Hanhart
syndrome)• Childhood systemic sclerosis
WORKUP
• Lab Studies: • screening (enzymatic determination of
phenylalanine, and the Guthrie test as a bacterial inhibition assay)Perform screening on blood samples during the first week of life.
Imaging Studies:
• Perform cranial MRI in adults who have neurologic dysfunction; the most severely affected brain structures regarding volume loss are the cerebrum, corpus callosum, hippocampus, and pons.
• Perform cranial magnetic resonance (MR) spectroscopy to determine brain metabolite concentrations and brain compartmentation.
TREATMENT• Medical Care: • Treatment a diet low in phenylalanine
tyrosine supplementation is required for normal psychomotor development.
• BH4 supplementation (5-20 mg/kg) has been applied in PKU treatment,
• Consultations:
Consult a psychologist for assessment and management of mental disorders.Consult a nutritionist for dietary instructions.
DietInstruct patients to do the following:
•Selectively restrict phenylalanine consumption (ie, approximately 250-550 mg/d or 40-60 mg/kg/d in newborns).•Supplement the diet with tyrosine. •Avoid the use of products containing aspartame (artificial sweetener).•Aspartame is used widely in medicines, vitamins, beverages, and many other products.•Eliminate all high-protein foods (eg, meat and meat products, milk and dairy products, nuts, legumes), and introduce low-protein foods (eg, fruits, vegetables, breads). Activity: Advise continuation of normal activity in patients who are adequately treated.
• Complications:
Agoraphobia is a complication.
Prognosis:
The prognosis for normal intelligence is good when patients have been put on a diet low in phenylalanine in the first month of life.
• Patient Education:
Teach patients how to initiate and continue the diet.Educate women with PKU about the risks of untreated pregnancy and the benefits of dietary treatment.
