CLINICAL SIGNIFICANCE of PLASMA AND CSF AMINO ACIDS:

Deficiency of a single in a metabolic pathway may produce its effects in several ways: (A) accumulation of the substrate acted on by the enzyme; (B) deficiency of the products of the enzyme reaction; (C) diversion through an alternative pathway, leading to production of abnormal or abnormally concentrated metabolites. Aminoacidopathies may be specific (a genetic defect involving one or a group of related amino acids) or nonspecific involving a number of unrelated amino acids). Examples: an elevation of alanine and in plasma would indicate (alanine is a precursor to tyrosine); an elevation of many amino acids is frequently seen in patients with liver disorders. However, a diet high in fowl (chicken, turkey) may result in an asymptomatic elevation of methylhistidine. Clinical symptoms of aminoacidopathies are usually identified early in life due to comprehensive newborn screening programs and may include lethargy, hyperactivity, retarded mental and physical development, convulsions, and early death.

Clinical Interest and Association of Amino Acids with Inborn Errors and Other Disorders (s) Disorder(s), other (diet, age, etc) Alanine Tyrosinemia (p), transport defects* (u) Alloisoleucine MSUD (p) (Pathognomonic for MSUD) Anserine (u); high meat diet Hyperargininemia (p), transport defects* (u) Argininosuccinic Acid Argininosuccinic Aciduria (u); hyperornithinemia Dicarboxylic (u) Carnosinemia (u); high meat diet Citrulline (p,u); arginosuccinic aciduria (u); hyperargininemia (u) Cystathionine Cystathionuria (u); young infants (u); ; neuroblastoma; liver cirrhosis Cystine (u), Cystinemia (p), Hyperargininemia (p), Cystinlysinuria (u) Hyperamonemia associated with Non-Ketotic hyperglycinemia (p,u,c); organic acidopathies (p,u); transport defects*; valproic acid (u) (p,u), chicken/fowl diet (p,u) Homocystine (u), (p 5-100 x normal), CSF homocystine elevated, methymalonic aciduria, cystathionine synthetase deficiency Hydroxyproline Hydroxyprolinemia (u), newborns, chronic uremia, bone disease (u) MSUD (i,p); ketotic hypoglycemia (p,u), chronic liver disease (p,u) See isoleucine (p,u); transport defect*(u), cystinuria (u) Methionine Homocystinuria (u); methionine adenyl transferase deficiency (p,u); tyrosinosis (u) 1-methylhistidine Chicken, fowl diet, starvation (u) 3-methylhistidine Chicken, fowl diet, starvation (u)

Ornithine Hyperornithinemia (p), hyperammonemia (p), homocitrullinuria (u), associated with increased glutamine (p,u) PKU and variants (p,u); transient tyrosinemia (p,u); tyrosinemia (p,u) Phosphoethanolamine Hypophosphatasia (u) (p,u); maturational defect Serine (decrease p) phosphoserine aminotransferase deficiency, serine deficiency, (increase u) Hartnujp Threonine (increase p,c) pyridoxamine 5’-phosphate deficiency, (u) Hartnup Taurine Acute liver failure (u); high protein intake (u); maturational delay in prematures (u,p) Hartnup's disease (u) Tyrosine Tyrosinemia (p,u), Tyrosinosis (p,u), chronic liver disease (p,u); transient neonatal tyrosinemia (p); generalized amino aciduria* (u); Fructosemia (u) MSUD (u,p); (p)

*Hartnup's Disease, , Renal Tubular Aminoaciduria u = amino acid elevated p = plasma amino acid elevated c = CSF

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