At a Glance Pyruvate Carboxylase Deficiency (PC) is an inherited disorder of metabolism of gluconeogenesis. This mitochondrial enzyme converts pyruvate to oxaloacetate, and a defect leads to elevations of lactic acid, hypoglycemia, and hyperammonemia. PC is inherited in an autosomal recessive manner, meaning the individual inherited two abnormal copies of the PC gene (each gene…
At a Glance Phenylketonuria (PKU) is an inherited disorder of metabolism of the essential amino acid phenylalanine due to a defect in phenylalanine hydroxylase (PAH). Phenylalanine (PHE) is present in all protein containing foods, and individuals with PKU will have elevated levels of PHE. PKU is inherited in an autosomal recessive manner. Autosomal recessive inheritance…
At a Glance Tyrosinemia (also known as Tyrosinemia type 1, Hereditary Tyrosinemia, or Hepatorenal Tyrosinemia) is an inherited disorder of metabolism of the essential amino acid tyrosine due to a defect in fumarylacetoacetate hydrolase (FAH). Tyrosine (TYR) is present in all protein containing foods, and individuals with Tyrosinemia will have elevated levels of TYR. Urine…
At a Glance Maple Syrup Urine Disease (MSUD) is an inherited disorder of metabolism of the essential amino acids leucine, isoleucine, and valine due to a defect in branched-chain alpha-keto acid dehydrogenase complex. These three branched-chain amino acids (BCAA) are present in all protein containing foods, and individuals with MSUD will have elevated levels of…
At a Glance Hypermethioninemia is a finding of an elevated methionine on plasma amino acids analysis. The differential for methionine elevations includes homocystinuria caused by cystathionine β-synthase deficiency (CBS), methionine S-adenosyltransferase deficiency (MAT), glycine N-methyltransferase deficiency, S-adenosylhomocysteine hydrolase deficiency, and acquired or inherited liver disease. This chapter focuses primarily on narrowing this differential and MAT…
At a Glance Homocystinuria is most commonly due to a defect in sulfur-containing amino acid methylation cycle. This cycle includes methionine, homocysteine (HCY), and cysteine. Elevations of homocysteine are most frequently seen in cystathionine β-synthase (CBS) deficiency, but may also be seen in methylenetetrahydrofolate reductase (MTHFR) deficiency and disorders of cobalamin metabolism. Homocystinuria due to…
At a Glance Cystathionuria is an inherited deficiency in the enzyme γ-cystathionase (CTH, also known as cystathionine gamma-lyase). This enzyme is a part of the sulfur-containing amino acid metabolism, including methionine, homocysteine (HCY), and cysteine. Defects in CTH activity result in elevations of cystionine that can be detected in plasma and urine. Cystathionuria is inherited…
At a Glance N-acetylglutamate synthase deficiency (NAGS) is an inherited disorder of urea cycle metabolism. Urea cycle disorders are a collection of eight enzymes involved in waste nitrogen excretion as urea, including carbamyolphosphate synthetase I deficiency (CPS1), ornithine transcarbamylase deficiency (OTC), citrullinemia type 1 (CIT1), citrin deficiency (including citrullinemia type 2, CIT2), argininosuccinic acidemia (ASA),…
At a Glance Cabamyolphosphate synthetase I deficiency (CPS1) is an inherited disorder of urea cycle metabolism. Urea cycle disorders are a collection of eight enzymes involved in waste nitrogen excretion as urea, including N-acetylgutamate synthase deficiency (NAGS), ornithine transcarbamylase deficiency (OTC), citrullinemia type 1 (CIT1), citrin deficiency (including citrullinemia type 2, CIT2), argininosuccinic acidemia (ASA),…
At a Glance Ornithine transcarbamylase deficiency (also known as OTC) is an inherited disorder of urea cycle metabolism. Urea cycle disorders are a collection of eight enzymes involved in waste nitrogen excretion as urea including N-acetylglutamate synthase deficiency (NAGS), carbamyol phosphate synthetase I deficiency (CPS1), citrullinemia type 1 (CIT1), citrin deficiency (including citrullinemia type 2;…
