Inborn Errors of Metabolism: Part 2: Specific Disorders

Abstract

1. Paul A. Levy, MD* 1. *Assistant Professor of Pediatrics and Pathology, Children's Hospital at Montefiore, Bronx, NY The following article is included online only as a second part of the article “Inborn Errors of Metabolism: Part 1.” There is no one prototypical disorder of amino acid metabolism; each disorder has its own unique collection of symptoms. Four well-described amino acid disorders have been chosen as examples of this group. Phenylketonuria, a disorder of phenylalanine metabolism, leads to intellectual disability if untreated. Maple syrup urine disease involves an enzyme common to the degradation of the branched-chain amino acids (leucine, isoleucine, and valine). Although there are five subtypes of maple syrup urine disease, the classic form has a neonatal onset and generally progresses from poor feeding to coma and death if not treated. Tyrosinemia also has multiple subtypes. Hepatorenal tyrosinemia (type I) may present with liver failure (elevated transaminase concentrations, hyperbilirubinemia, coagulopathy, ascites, and gastrointestinal bleeding) as well as kidney involvement (tubular dysfunction) and peripheral nerve involvement (painful crises, weakness or paralysis). Type II tyrosinemia is an oculocutaneous form of the disease that has corneal lesions and skin findings. Homocystinuria, most commonly caused by cystathionine beta-synthase deficiency, presents with ocular (ectopia lentis), skeletal (marfanoid features such as dolichostenomelia and arachnodactyly), vascular (thromboembolic), and central nervous system (intellectual disability, stroke, and seizures) abnormalities. When an amino acid disorder is suspected, measurement of plasma amino acids generally is sufficient to make the diagnosis. Assessment of urine amino acids can be helpful for homocystinuria and some abnormalities of amino acid transport (cystinuria, dicarboxylic amino aciduria) that affect the kidneys and for detecting generalized amino aciduria found with some kidney disease and mitochondrial disorders. The degradation of amino acids results in their deamination, generating ammonia as the waste nitrogen. The urea cycle removes the excess ammonia by generating urea, which is eliminated in the urine. Six disorders of the urea cycle are known. …