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Chapter 144. Other Disorders of Amino Acid Metabolism

Jean-Marie Saudubray

Imidazole-Dipeptide Metabolism Defects: Carnosine and Homocarnosinemia

The enzyme defects, clinical manifestations, metabolic disturbances, and treatment of these disorders are presented in Table 144-1.

Table 144-1. Miscellaneous Amino Acid Disorders
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Table 144-1. Miscellaneous Amino Acid Disorders
DisorderEnzyme DefectClinical PresentationMetabolic Derangement and Diagnostic TestsTreatment
Carnosinemia1,2Serum carnosinaseMental retardation, seizures, or asymptomatic (no disease)Plasma and urines AAC: high carnosine and anserine on meat-containing dietNone
ARNo 1-methylhistidine excretion
Low carnosinase activity in serum
Homocarnosinosis3Serum carnosinaseSpastic diplegia, mental retardation, or asymptomatic (no disease) similar to carnosinemiaHomocarnosine 30 to 50 times normal in CSFNone
Low carnosinase activity in serum
Prolidase deficiency4Peptidase D (exopeptidase prolidase)Skin lesions, recalcitrant ulcerations on of the lower legs from infancy to late adolescence.Massive excretion of imidodipeptide (dipeptides containing N-terminal proline or hydroxyproline, particularly glycylproline) detected by partition and elution chromatography and by direct chemical-ionization mass spectrometryOral ascorbate
ARCharacteristic facies Enzyme analysis in hemolysates, leucocytes, or fibroblastsManganese (cofactor of the enzyme): questionable efficiency
Recurrent infectionsDNA testing
Risk factor for the development of systemic lupus erythematosus
Histidinemia5Histidine ammonia-lyaseProbably normal variantHyperhistidinemia and histidinuria at AACNone
Urocanase deficiency6UrocanaseProgressive psychomotor retardation seizuresHigh urocanic excretionNone
Enzyme analysis
Acetyl aminoaciduria7Aminoacylase IStill undefined; probably normal variantN-acetyl amino acid excretion at AACNone
AREnzyme analysis
DNA testing
N-Acetylaspartic aciduria8Aspartoacylase (aminoacylase II)Canavan diseaseAcetyl aspartic aciduria at organic acid analysis by GCMSNone
AREnzyme analysis in fibroblasts
DNA testing
Trimethylaminuria (TMA) AR9,10Flavin-containing monooxygenase 3 (FMO3)Episodic offensive body odor, after sweating or after egg or fish ingestion (fish odor syndrome)High excretion of trimethylamine (TMA) with elevation of TMA/TMA-N-oxide measured by NMR spectroscopy on urines after a dietary load in TMACounseling and adjustments to diet and lifestyle
DNA testingLow choline diet
2-week courses of metronidazole
Dimethylglycinuria11,12Dimethylglycine dehydrogenaseUnpleasant fish odor of the body and urinesMassive dimethylglycine accumulation in plasma and urines measured by NMR spectroscopyRestriction of dietary choline
DNA testing

AAC, amino acid chromatography; AR, autosomal recessive.

Imidazole dipeptides derive their name from the imidazole ring of histidine. Carnosine (beta alanine histidine) is found in skeletal muscles and the brain, where it may be a neurotransmitter. It is hydrolyzed by two isozymes. Cytosolic carnosinase displays a very broad dipeptidase activity but does not hydrolyze anserine or homocarnosine. Serum carnosinase, also found in the cerebrospinal fluid, hydrolyzes carnosine and anserine but hydrolyzes homocarnosine very poorly. Anserine (beta alanine-1-methylhistidine) is normally absent from human tissues and body fluids but may be derived from the diet and is found in patients with serum carnosinase deficiency. Homocarnosine (gamma aminobutyryl histidine) is a brain dipeptide. It is hydrolyzed by serum but not by cytosolic carnosinase. The physiological ...

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