Disorders of Amino Acid Metabolism



Disorders of Amino Acid Metabolism





Incidence: phenylketonuria 1:10,000; defective amino-acid transport 2:10,000; all other aminoacidopathies <8:100,000.

Neurologic damage frequently preventable with early treatment; mass newborn screening important for early diagnosis.


Phenylketonuria (PKU)

Phenylalanine hydroxylase deficiency. Autosomal recessive. Impaired hepatic hydroxylation of phenylalanine to tyrosine. Phenylalanine accumulates in blood and is neurotoxic. If untreated: mental retardation, seizures, imperfect hair pigmentation.


Pathogenesis and Pathology



  • Classic PKU: enzyme activity completely or nearly completely absent.


  • Pathology: defective brain maturation; defective myelination; diminished or absent pigmentation of substantia nigra, locus ceruleus.


Clinical Features

Wide range of clinical, biochemical severity. Classic form: normal at birth; vomiting, irritability in first 2 months; delayed intellectual development by 4 to 9 months; seizures (infantile spasms, later grand mal).



  • Typical features: blond hair, blue eyes, rough and dry skin, eczema, musty odor (phenylacetic acid).


  • Neurologic features: microcephaly; mental retardation; increased muscle tone; tremor of hands; EEG hypsarrhythmia, foci of spikes or polyspikes; MRI: areas of increased T2 signal in white matter.


Jul 27, 2016 | Posted by in NEUROLOGY | Comments Off on Disorders of Amino Acid Metabolism

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