Early diagnosis of inborn errors of metabolism

Introduction: Inborn errors of metabolism may already occur in the early newborn phase. Clinical symptoms may be: seizures, apnea, muscular hypotonia, cardiomyopathy, hepatopathy, extrapyrimidal movment disorders or respiratory insufficiency. Later on an ataxia, a retardation or an nontreatable grand mal epilepsia and in adults heavy cardiological or atherosklerotic symptoms, liver and kidney problems may occur.

Methods: Gaschromatography with a mass selective detector (GC/MS) is the common basis for a metabolic screening. Meanwhile we have developed further screening methods with tandem mass spectrometry (TMS) in urine, dried blood spots and plasma for the diagnosis of inborn errors of metabolism. A broad screening technology is the only possibility for a time- and cost effective diagnosis.

Results: Peroxisomal disorders, defects in creatine metabolism, ureacycle and purine-pyrimidine defects as well as aminoacidurias and defects in cobalamin metabolism will be screened quick and reliable. Run time is between 1 and 10 minutes. Spezific key metabolites like guanidinoacetate, creatine, ureidopropionic acid, sulfocysteine, pipecolic acid, phytanic acid and very long chain fatty acids (VLCFA) will be dedetced by extended neurometabolic screening. By this way peroxisomal diseases like Zellweger-syndrome, Fabry diesease, Pompe disease and further lysosomal diseases will be detected, too.

Conclusions: The efficiency of making a diagnosis will be increased obviously by using specific key metabolites.