Differential diagnosis of (inherited) amino acid metabolism or transport disorders

Abstract

Summary. Disorders of amino acid metabolism or transport are most clearly expressed in urine. Nevertheless the interpretation of abnormalities in urinary amino acid excretion remains difficult. An increase or decrease of almost every amino acid in urine can be due to various etiology. To differentiate between primary and secondary aminoacido-pathies systematic laboratory investigation is necessary. Early diagnosis of disorders of amino acid metabolism or transport is very important, because most of them can be treated, leading to the prevention of (further) clinical abnormalities. In those disorders, which cannot be treated, early diagnosis in an index-patient may prevent the birth of other siblings by means of genetic counseling and prenatal diagnosis.Primary aminoacidopathies can be due to genetically determined transport disorders and enzyme deficiencies in amino acid metabolism or degradation. Secondary aminoacidopathies are the result of abnormal or deficient nutrition, intestinal dysfunction, organ pathology or other metabolic diseases like organic acidurias.A survey of amino acid metabolism and transport abnormalities will be given, illustrated with metabolic pathways and characteristic abnormal amino acid chromatograms.

Impairments in pyridoxine-dependent sulphur amino acid metabolism are highly sensitive to the degree of vitamin B6 deficiency and repletion in the pig

“…Liver thiol and PLP concentrations were expressed on a per gram of liver basis. Plasma-free methionine, serine and glycine were measured via ion-exchange chromatography (LKB 4151 alpha-plus amino acid analyzer, Pharmacia, Cambridge, UK), with postcolumn ninhydrin derivitization, using methods as previously described (Blom and Huijmans, 1992). For all enzyme assays, initial experiments were conducted to establish optimal conditions for protein assay duration.…”

Quantitative Methods for Amino Acid Analysis in Biological Fluids

“…Amino acids are identified and quantified by relating the peaks to an internal standard and by comparison with a standard mixture chromatographed in parallel. (I) aspartic acid; (2) threonine; (3) serine; (4) glutamine; (5) glycine; (6) alanine; (7) valine; (8) cystine; (10) tyrosine; (//) phenylalanine; (12) ammonia; (13) ornithine; (14) lysine; (15) histidine; (16) 3-methylhistidine; (17) (2) urea; (3) aspartic acid; (4) threonine; (5) serine; (6) asparagine; (7) glutamic acid; (8) glutamine (9) glycine; (10) alanine; (1I) citrulline; (12) valine; (13) cystine; (14) methionine; (16) isoleucine; (17) leucine; (18) tyrosine; (19) phenylalanine; (20) ammonia; (21) ornithine; (22) lysine; (23) histidine; (24) tryptophan; (25) arginine; IS = Internal Standard (norleucine). …”

“…52 Cystine, ornithine, lysine and homocystine produce disubstituted derivatives and their absorbance at 254 nm is twice that of other amino acids. Cystine elutes close to a reagent peak with which it may be confused.s' Degradation to phenylthiohydantoin analogues is prevented by maintaining alkaline conditions and use of a (1) glutamic acid; (2) serine; (3) glycine; (4) glutamine; (5) taurine; (6) histidine; (7) citrulline and ammonia; (8) threonine; (9) alanine; (10) arginine; (1 I) proline; (12) tyrosine; (13) valine; (15) isoleucine; (16) a//oisoleucine; (17) leucine; (18) phenylalanine; (19) tryptophan; (20) ornithine; (21) lysine; (14) refrigerated autosampler. The complex derivatization procedure was a problem, but has been simplified with a commercial system (Pico-Tag, Waters, Millipore, UK).I,13,24 The two main advantages compared with OPA procedures are that proline and hydroxyproline are detected, and that, except for sarcosine, the PTC-amino acid adducts are stable for up to 24 h at room temperature and 2 months at -20°C.13,52 However, sensitivity is 20-50 times less (20-50 pmol) than with OPA.28 Rapid deterioration of the HPLC column can be a problem.…”

“…Urinary tyrosine may be increased in premature or small babies on a high protein intake. 11,12,128,145,155 …”

“…Diet influences excretion of some amino acids. ll , 12,15,128,146,158 These causes of secondary amino acid abnormalities, and artefacts from poor samples, must be considered, before making a diagnosis of an inherited defect. Amino acid disturbances often accompany inherited disorders of other metabolites, for example, increased alanine in congenital lactic acidaemia, glutamine in urea cycle defects, glycine in organic acidaemias.…”