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

Mel Mcsweeney,Maureen Cleary,Stefan Krywawych,Simon Heales

doi:10.1002/jmd2.12102

Abstract

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.

Highlights

Inborn errors of metabolism (IEMs) occur in different pathways, including the metabolism of amino acids, carbohydrates, and fatty acids
The specific characteristic acylcarnitine esters, diagnostic for LCHADD, IVA, and MMA were clearly elevated in the earwax from patients with these conditions raising the possibility that this tissue could be suitable for diagnostic purposes
Earwax acylcarnitines in individuals with MCADD requires further investigation to establish whether earwax octanoylcarnitine and decanoylcarnitine are raised and thereby of diagnostic value in these patients at time of acute decompensation rather than the well patients studied here

Summary

| INTRODUCTION

Inborn errors of metabolism (IEMs) occur in different pathways, including the metabolism of amino acids, carbohydrates, and fatty acids. A failure to sustain an energy supply dependent upon fat metabolism, on occasions when carbohydrate is limiting, can manifest at any age with a wide clinical presentation including sudden infant death syndrome (SIDS) At autopsy, these infants tend to demonstrate fat deposits in cardiac and skeletal muscle in addition to hepatic tissue. Experience, postmortem blood specimens consistently demonstrate raised free carnitine (C0), acetylcarnitine (C2), butyrylcarnitine (C4), hydroxybutyrylcarnitine (OHC4) with variable concentrations of the other longer chain carnitine esters species (unpublished observations). This raises the possibility of a missed diagnosis. To assess the potential value of earwax as a tissue for diagnosing IEMs, we performed a proof of principle study to evaluate whether this material demonstrates the presence of characteristic disease-specific diagnostic markers

| METHODS

| RESULTS

Findings

| DISCUSSION