Earwax: A potentially useful medium to identify inborn errors of metabolism?

Earwax was investigated as a source to identify patients' different inborn errors of metabolism (IEMs). Acylcarnitines, amino acids, and guanidino metabolites were measured from 28 treated patients with 11 different metabolic disorders including 3 organic acidaemias, 2 fatty acid oxidation defects, 6 amino acid disorders, and 1 peroxisomal abnormality. On the basis of the ratio of different acylcarnitine species relative to free carnitine, isovaleric acidaemia, methylmalonic acidaemia, and long-chain hydroxyacylCoA dehydrogenase deficiency could be discriminated from the other disorders. For amino acids, neither creatinine nor alternative amino acid proved suitable reference standards against which results could be expressed. However, argininosuccinate and alloisoleucine were present in significantly elevated concentrations in two patients with argininosuccinate lyase deficiency and two patients with branched-chain ketoacid dehydrogenase deficiency. This study has raised the potential of earwax for investigation of IEMs and may also have role in postmortem investigations. In view of its limited invasiveness, earwax also may have a role as a material to monitor treatment responses and compliance in patients with IEMs.

NMR spectroscopy of aminoacylase 1 deficiency, a novel inborn error of metabolism.

Aminoacylase 1 deficiency is a novel inborn error of metabolism. The clinical significance of the deficiency is under discussion, as well as the possible consequences of the defect for brain metabolism and function. This study includes the five originally published cases as well as three novel ones. NMR spectroscopy of urine, serum and cerebrospinal fluid has been used to study these patients. A typical profile with 11 accumulating N-acetylated amino acids was observed in urine from the patients. The concentration of most of the accumulating metabolites is typically 100-500 micromol/mmol creatinine. Two additional minor N-acetylated metabolites remain unidentified. The concentrations of the accumulating metabolites are <20 micromol/L in serum from the patients. Interestingly we found no evidence of an increased concentration of N-acetylated amino acids in the cerebrospinal fluid from one patient. Our data define aminoacylase 1 deficiency at the metabolite level providing a specific urinary profile of accumulating N-acetylated amino acids.