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.
Diagnosis and Differential Diagnosis
Most identified through newborn screening (blood phenylalanine level).
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