Metabolic defects in amino acid metabolism
The inherited defects of AA metabolism if stay
untreated result in mental retardation or other
developmental abnormalities because of the
harmful accumulation of metabolites.
1.Phenylketonuria (PKU)
The most common inborn error of amino acid metabolism (prevalence 1:15,000).
Due to phenylalanine hydroxylase deficiency
Biochemical changes: accumulation of
phenylalanine (and a deficiency of tyrosine).
Tyr cannot be synthesized from Phe and
becomes an essential amino acid.
o Patients should obtain Tyrosine from
diet.
Caused by any of 100 or more different
mutations in the gene that codes for
phenylalanine hydroxylase (PAH).
Due to the accumulation of Phe it will be
converted to other metabolites such as:
phenyllactate, phenylacetate, and
phenylpyruvate that can cross the BBB and
cause mental retardation.
1|Page
, Characteristics of classic PKU:
1. Elevated phenylalanine in tissues, plasma, and urine.
2. The characteristic musty “mousey” urine odor due to
phenyllactate, phenylacetate, and phenylpyruvate
3. CNS symptoms: Mental retardation (IQ < 50), failure to
walk or talk, seizures, hyperactivity, tremor,
microcephaly, and failure to grow
4. Hypopigmentation: fair hair, light skin colour, and blue
eyes because the hydroxylation of Tyr by tyrosinase
(the first step in melanin formation) is competitively
inhibited by the high levels of Phe.
After birth does the neonatal has mental retardation?
Not yet. Why?
At birth, infants with PKU have normal blood levels of Phe because the
mother clears the extra Phe through placenta thus PKU neonatal lack of
symptoms.
PKU is a genetic disease but can we reduce its symptoms and avoid
mental retardation?
Yup, through neonatal screening programmes, after birth usually a
several screening is done one of them to measure the phenylalanine
hydroxylase so we can early diagnose the PKU neonatal .
Exposure protein feeding for 24–48 hours elevates Phe, thus, screening
should be done after this to avoid false negatives.
2|Page
The inherited defects of AA metabolism if stay
untreated result in mental retardation or other
developmental abnormalities because of the
harmful accumulation of metabolites.
1.Phenylketonuria (PKU)
The most common inborn error of amino acid metabolism (prevalence 1:15,000).
Due to phenylalanine hydroxylase deficiency
Biochemical changes: accumulation of
phenylalanine (and a deficiency of tyrosine).
Tyr cannot be synthesized from Phe and
becomes an essential amino acid.
o Patients should obtain Tyrosine from
diet.
Caused by any of 100 or more different
mutations in the gene that codes for
phenylalanine hydroxylase (PAH).
Due to the accumulation of Phe it will be
converted to other metabolites such as:
phenyllactate, phenylacetate, and
phenylpyruvate that can cross the BBB and
cause mental retardation.
1|Page
, Characteristics of classic PKU:
1. Elevated phenylalanine in tissues, plasma, and urine.
2. The characteristic musty “mousey” urine odor due to
phenyllactate, phenylacetate, and phenylpyruvate
3. CNS symptoms: Mental retardation (IQ < 50), failure to
walk or talk, seizures, hyperactivity, tremor,
microcephaly, and failure to grow
4. Hypopigmentation: fair hair, light skin colour, and blue
eyes because the hydroxylation of Tyr by tyrosinase
(the first step in melanin formation) is competitively
inhibited by the high levels of Phe.
After birth does the neonatal has mental retardation?
Not yet. Why?
At birth, infants with PKU have normal blood levels of Phe because the
mother clears the extra Phe through placenta thus PKU neonatal lack of
symptoms.
PKU is a genetic disease but can we reduce its symptoms and avoid
mental retardation?
Yup, through neonatal screening programmes, after birth usually a
several screening is done one of them to measure the phenylalanine
hydroxylase so we can early diagnose the PKU neonatal .
Exposure protein feeding for 24–48 hours elevates Phe, thus, screening
should be done after this to avoid false negatives.
2|Page
