Amino acid disorders

Table 3.1.1 Disorders of organic acid metabolism (in alphabetical order). This table does not include disorders with primary accumulation of amino acids, disorders of mitochondrial fatty acid oxidation, or primary lactic acidemias. Co A Coenzyme A, FAD flavin adenine dinucleotide...

Where no effective treatment exists at present for some inborn errors of metabolism, and where these disorders are associated with severe illness, mental retardation, or early death, the prenatal diagnosis of the diseased fetus by amniotic fluid enzyme analysis is now possible (MIO, Mil, M12). These new developments in the field of transabdominal amniocentesis, coupled with more liberal abortion laws, can serve to reassure families with a previous history of a fatal disease that their offspring will be physiologically normal. As applied to the field of amino acid disorders, enzyme analysis of cultured amniotic fluid cells has been used to diagnosis potential cases of homocystinuria (Fig. 51) and... 

Unlike other disease entities, excejit for canine cystinuria, no other nonhuman inherited amino acid disorders have been uncovered. In place of animal studies, increasing emphasis is being placed on the use of cultured explants of tissues removed from patients with hereditary metabolic disease. Cultured explants of skin, leukocytes, and erythrocytes have been used to study the metabolism of such disorders as citrullinemia, branch-chain ketoaciduria, cystinosis, homocystinuria, and isovalericacidemia (S18). 

Work is presently in progress dealing with the detection and investigation of those amino acid disorders that affect catabolism of the carbon skeleton of amino acids (G26). Such conditions are often difficult to detect because the accumulated metabolites do not react with ninhydrin and methods for their detection are not available in most clinical laboratories. The greater availability of techniques such as gas-liquid chromatography should lead to the discovery of many more inborn errors of amino acid metabolism. 

H2. Handley, D. A., and Arney, G. K., Plasma cell myeloma and associated amino-acid disorder. Arch. Intern. Med. 120, 353-355 (1967). 

Blood specimens are recommended for investigation of aminoacidopathies because amino acid concentrations are fairly stable in blood, urine amino acids analysis, on the other hand, is appropriate for disorders of amino acid renal transport such as cystinuria. Amino acid analysis in cerebral spinal fluid may be appropriate to aid in diagnosis (i.e., nonketotic hyperglycinemia) and management (i.e., cerebral amino acid disorders) of various IMD. The composition of an... 

Amino acid disorders maple syrup urine disease, homocystinuria, cystinuria, alkaptonuria and albinism... 

Amino acid disorders Metabolism of amino acids and porphyrins 103... 

Clift, J., Hall, S. K., Carter, R. A., Denmeade, R., and Green, A. (1994). An improved thin-layer chromatography technique for neonatal screening for amino acid disorders using dried blood spots. Screening 3 39-43. 

Amniotic fluid has limited value in prenatal diagnosis for the aminoacid-opathies. Unlike the organic acid disorders, in most amino acid disorders the metabolites do not accumulate before birth. Abnormal amino acid patterns in amniotic fluid have only been found in two of the urea cycle disorders, namely argininosuccinate lyase deficiency (argininosuccinic acidemia) and argininosuccinate synthetase deficiency (citrullinemia). 

For the diagnosis of most amino acid disorders, morning fasting blood specimens are preferred. Samples from young infants, who are fed at frequent intervals, should be collected immediately before the next scheduled feeding. For hyperammonemia screening, postprandial blood is more suitable since an elevation of blood ammonia may be intermittent and present only in the fed state. 

Routine metabolic screening for amino acid disorders usually includes several simple general preliminary tests and chromatographic analysis of amino acids. Because of the wide availability of amino acid analyzers, semi-quantitative amino acid screening is now used less often. One-dimensional paper or thin-layer chromatographic screening for amino acids is... 

For prenatal diagnosis, amniotic fluid can be used to identify acylcarni-tines characteristic of certain branched-chain amino acid disorders. Cultured amniocytes or chorionic villous cells can be used with in-vitro substrate loading for diagnosis of fatty acid and branched-chain amino acid disorders as described earlier for fibroblasts [13]. 

Because of the rather specialized applications of amino acid testing using MS/MS, general guidelines are not applicable. The individual chapters referring to each amino acid disorder are the best source of information. A new MS/MS test for sulfocysteine is now available, and should be included in the differential for intractable seizures in the neonate. 

Vivian E. Shih Harvard Medical School Massachusetts General Hospital East Amino Acid Disorders Laboratory Building 149, 13th Street Boston, MA 02129 USA... 

Note-. (1-9) Organic acid disorders, (10-14) fatty acid oxidation disorders, (15-20) amino acid disorders, (21-23) hemoglobinopathies, (24 and 25) endocrinopathy, (26) other inborn error of metabolism, (27) carbohydrate disorders, (28) miscellaneous genetic conditions, and (29) infectious diseases. MS/MS tandem mass spectrometry, HPLC high pressure hquid chromatography, lEF isoelectrofocusing, RIA radioimmuno assay, and ELISA enzyme-linked immunosorbent assay. 

Demineralised whey is used to correct the casein whey ratio in several modified (whey-based) milks containing 1 5 to 1 8 % protein examples are listed in Table 1. These milks more closely mimic the amino acid content of human milk, since the proportion of cystine is increased while those of methionine, phenylalanine and tyrosine are lowered. Whey-based modified milks appear to promote better growth in low birth weight infants, though the exact mechanism for this effect is still uncertain at present . In the absence of human milk the whey-based modified milks such as Gold Cap SMA (Wyeths), Osterfeed (Farley), Premium (Cow Gate) and Nan (Nestles) are recommended for the prevention and treatment of neonatal amino acid disorders and in my opinion are preferable to diluted cows milk or casein-based formulae for normal neonates. 

Roesel, R.A., Coryell, M.E., Blankenship, P.R., Thevaos, T.G. and Knowlton Hall, W. (1980), Interference of methenamine mandelate in screening for organic and amino acid disorders. Clin. Chim. Acta, 100,55. 

---