Inherited metabolic disorders

The a-oxidation pathway is defective in Refsum s disease, an inherited metabolic disorder that results in defective night vision, tremors, and other neurologic abnormalities. These symptoms are caused by accumulation of phytanic acid in the body. Treatment of Refsum s disease requires a diet free of chloro-... 

Inherited Metabolic Disorders Errors of Phenylalanine and Tyrosine Metabolism L. I. Woolf... 

Reference Intakes (DRIs). In the past, the recommended dietary allowances (RDAs), which are the levels of intake of essential nutrients that are considered to be adequate to meet the known nutritional needs of practically all healthy persons, were the primary reference value for vitamins and other nutrients. The DRIs also include other reference values, such as the estimated average requirement (EAR) and the adequate intake (AI). The RDA, EAR, and AI reference standards define nutritional intake adequacy. Since these recommendations are given for healthy populations in general and not for individuals, special problems, such as premature birth, inherited metabolic disorders, infections, chronic disease, and use of medications, are not covered by the requirements. Separate RDAs have been developed for pregnant and lactating women. Vitamin supplementation may be required by patients with special conditions and for those who do not consume an appropriate diet. 

Gout. An inherited metabolic disorder occurring especially in men, characterized by a raised but variable blood uric acid level, recurrent acute arthritis of sudden onset, deposition of crystalline sodium urate in connective tissues and articular cartilage, and progressive chronic arthritis. 

To diagnose or exclude inherited metabolic disorders in individual patients. In this situation the increased concentration of the key metabolite may be quite prominent and is typically at least one order of magnitude greater than the reference range (e.g. phenylalanine > 1000 pmol/1 compared with a reference range of 42-110 pmol/1 [4]. 

Roe CR, Roe DS (1999) Recent developments in the investigation of inherited metabolic disorders using cultured human cells. Mol Genet Metab 68 243-257... 

CFD is further associated with the following inherited metabolic disorders 5,10-methylen-tetrahydrofolate reductase (MTHFR) deficiency [7], 3-phos-phoglycerate dehydrogenase (PGDH) deficiency [8], dihydropteridine reductase (DHPR) deficiency [9], as well as with Rett syndrome [10], and Aicardi-Gou res Syndrome [11]. Furthermore, folate deficiency may be associated with congenital folate malabsorption, severe malnutrition, and formiminotransferase deficiency. 

DNA studies aim to provide ultimate proof of a disease in a patient with an inherited metabolic disorder and should not usually lead to follow-up assays. Indeed, enzyme assays and other functional studies are often easier, cheaper and have a higher sensitivity than molecular studies. When possible, enzyme assays should be performed prior to the DNA test. As always exceptions prove the rule. 

Both trien745 and 2,3,2-tet856 have been used to treat Wilson s disease in patients sensitive to D-penicillamine. Wilson s disease results from an inherited metabolic disorder which leads to the... 

Inborn errors of metabolism are inherited metabolic disorders caused by the absence of an enzyme in a metabolic pathway. Alkaptonuria is caused by the lack of homogentisate oxidase and is harmless, whereas phenylketonuria, which is due to a lack of phenylalanine hydroxylase, can cause severe mental retardation. 

Biotinidase deficiency represents a readily di-agnosable inherited metabolic disorder for which the symptoms can be prevented or ameliorated with simple, direct therapy. If a child must have an inborn error of metabolism, then biotinidase deficiency is the disorder to have. 

Elemental analysis of body tissues and fluids by atomic absorption spectrometry with electrothermal atomisation has advanced significantly the understanding of the role of trace elements in clinical biochemistry. All of those aspects of metabolic processes that are affected by changes in the concentrations of accessible trace elements have been studied. These include deficiencies of essential trace elements as a result of inherited or acquired metabolic disorders, or from nutritional inadequacy and excesses of trace elements producing toxicity states as a result of inherited metabolic disorders involving essential trace elements or from the inappropriate exposure to, or ingestion of, non-essential trace elements. 

Robinson BH, MacKay N, Chun K, and Ling M (1996) Disorders of pyruvate carboxylase and the pyruvate dehydrogenase complex. Journal of Inherited Metabolic Disorders 19, 452-62. 

Ubbink JB (1997) The role of vitamins in the pathogenesis and treatment of hyperho-mocyst(e)inaemia. Journal of Inherited Metabolic Disorders 20,316-25. 

The application of GC-MS to the study of inherited metabolic disorders and pathological conditions is undoubtedly of expanding interest but it remains to be seen how effective it might be as a routine measure in the clinical diagnostic situation. 

Saudubray JM, Nassogne MC, de Lonlay P, Touati G. Clinical approach to inherited metabolic disorders in neonates an overview. Semin Neonatol 2002 7 3-15. 

Rashid ST et al (2010) Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest 120(9) 3127-3136... 

Certain metabolites of the pyrimidine pathway are excreted in excess of the normal in inherited metabolic disorders of the urea cycle. They include orotic acid, uridine, and uracil. Of these substances, only uracil is a normal constituent of urine, the other two either being absent or present in very small amount. They are readily detected qualitatively as dark bands at the appropriate Rf values when a paper chromatogram of the urine is examined under ultraviolet light. They may be estimated by an ion exchange method similar to that for urinary pseudouridine (R13). 

W22. Woolf, L. I., Inherited metabolic disorders Errors of phenylalanine and tyrosine metabolism. Advan. Clin. Chem. 6, 97-230 (1963). 

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