Aminoacidopathies

Aminoacidopathies are a group of inherited metabolic disorders characterized by abnormal levels of amino acids in blood and urine due to defects in amino acid transport, metabolism, or degradation. They include defects in amino acid catabolism, transport disorders, and some urea cycle abnormalities. The resulting imbalance can cause toxin accumulation or essential deficiency, leading to neurodevelopmental problems, metabolic crises, growth delay, neurological symptoms, and organ dysfunction if untreated.

Common examples include phenylketonuria (PKU), caused by deficiency of phenylalanine hydroxylase or its cofactor pathway, leading to elevated phenylalanine and reduced tyrosine; maple syrup urine disease (MSUD), due to impairment of the branched-chain α-keto acid dehydrogenase complex, with accumulation of leucine, isoleucine, and valine; and the urea cycle disorders (such as OTC or CPS1 deficiencies), which cause hyperammonemia from impaired nitrogen disposal. Other disorders include homocystinuria from cystathionine beta-synthase deficiency, causing elevated homocysteine and methionine with vascular and ocular risks; and Hartnup disease, a neutral amino acid transporter defect leading to pellagra-like symptoms from niacin deficiency. Tyrosinemias, due to defects in tyrosine degradation, present with liver and kidney involvement and require specific therapies.

Diagnosis relies on newborn screening and diagnostic workups using targeted plasma amino acid profiling, urine organic acids, and genetic testing. Tandem mass spectrometry and clinical assessment guide early identification. Treatment is usually dietary management to limit problematic amino acids, with disease-specific therapies such as tetrahydrobiopterin for some PKU cases, nitisinone for certain tyrosinemias, ammonia scavengers for urea cycle disorders, and sometimes liver transplantation in severe forms. Early detection and ongoing management improve outcomes.