Ans. a (Phenylketonuria) (Ref. Harrison's Internal Medicine 17th/Ch. 358)Inborn errors of amino acid metabolism associated with abnormal odourInborn error of metabolismUrine odorGlutaric acidemia (type II)Sweaty feet, acridHawkinsinuriaSwimming poolIsovaleric acidemiaSweaty feet, acridMaple syrup urine diseaseMaple syrup/Burnt sugarHypermethioninemiaBoiled cabbageMultiple carboxylase deficiencyTomcat urineOasthouse urine diseaseHops-likePhenylketonuriaMousy or mustyTrimethylaminuriaRotting fishTyrosinemiaBoiled cabbage, rancid butterTHE HYPERPHENYLALANINEMIAS# result from impaired conversion of phenylalanine to tyrosine.# The most common and clinically important is phenylketonuria (frequency 1:10,000), which is an autosomal recessive disorder characterized by an | concentration of phenylalanine and its by-products in body fluids and by severe mental retardation if untreated in infancy.# It results from | activity of phenylalanine hydroxylase (phenylketonuria type I).# The accumulation of phenylalanine inhibits the transport of other amino acids required for protein or neurotransmitter synthesis, reduces synthesis and increases degradation of myelin, and leads to inadequate formation of norepinephrine and serotonin.# Phenylalanine is a competitive inhibitor of tyrosinase, a key enzyme in the pathway of melanin synthesis, and ac- counts for the hypopigmentation of hair and skin.# Untreated children with classic phenylketonuria are normal at birth but fail to attain early developmental milestones, develop microcephaly, and demonstrate progressive impairment of cerebral function.# Hyperactivity, seizures, and severe mental retardation are major clinical problems later in life.# EEG abnormalities; "mousy" odor of skin, hair, and urine (due to phenylacetate accumulation); and a tendency to hypopigmentation and eczema are devastating clinical picture.# In contrast, affected children who are detected and treated at birth show none of these abnormalities.Treatment# To prevent mental retardation, diagnosis and initiation of dietary treatment of classic phenylketonuria must occur before the child is 3 weeks of age.# Dietary phenylalanine restriction is usually instituted if blood phenylalanine levels are >250 pmol/L (4 mg/dL).# Treatment consists of a special diet low in phenylalanine and supplemented with tyrosine, since tyrosine becomes an essential amino acid in phenylalanine hydroxylase deficiency.# With therapy, plasma phenylalanine cone should be maintained between 120 and 360 pmol/L (2 and 6 mg/dL).# Dietary restriction should be continued and monitored indefinitely..# Pregnancy risks can be minimized by continuing lifelong phenylalanine-restricted diets and assuring strict phenylalanine restriction 2 months prior to conception and throughout gestation.ConditionEnzyme DefectClinical FindingsInheritance1. Phenylketonuria type IPhenylalanine hydroxylaseMental retardation, microcephaly, hypopig- mented skin and hairs, eczema, "mousy" odorAR2. Phenylketonuria type IIDihydropteridine reductaseMental retardation, hypotonia, spasticity, myoclonusAR3. Phenylketonuria type III6-Pyruvoyl- tetrahydropterin synthaseDystonia, neurologic deterioration, seizures, mental retardationAR4. GTP cyclohydrolase I deficiencyGTP cyclohydrolase IMental retardation, seizures, dystonia, temperature instabilityAR5. Carbinolamine dehydratase deficiencyPterin-4-carbinolamine dehydrataseTransient hyperphenylalaninemia (benign)AR