Which of the following may be presenting feature of phenylketonuria?
Ans. a (Salaam spasms). (Ref: Harrison, Medicine, 16th ed., 2333)PHENYLKETONURIA# The 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 increased concentration of phenylalanine and its by-products in body fluids and by severe mental retardation if untreated in infancy.# It results from reduced 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 accounts 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.# Electroencephalographic abnormalities, "mousy" odour of skin, hair, and urine (due to phenylacetate accumulation);and a tendency to hypopigmentation and eczema complete the devastating clinical picture.# In contrast, affected children who are detected and treated at birth show none of these abnormalities.# 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 micromol/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.6# With therapy, plasma phenylalanine concentrations should be maintained between 120 and 360 micromol/L (2 and 6 mg/dL).# Dietary restriction should be continued and monitored indefinitely.# Some patients with milder forms of phenylketonuria (phenylalanine >120 pmol/L at presentation) show increased tolerance to dietary proteins and improved metabolic control when treated with tetrahydrobiopterin (20 mg/kg per day), an essential cofactor of phenylalanine hydroxylase.
Salaam spasms
Huntington's chorea
Diarrhoea
Haematemesis
Proteins and Amino Acids