APPLICATION OF MASS SPECTROMETRY IN THE DIAGNOSIS OF
INBORN ERRORS OF METABOLISM
Luo X1,2, Wang M1
1 Department of Pediatrics, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology, Wuhan, China
2 Department of Paediatrics, Faculty of Medicine, University of
Toronto, Toronto, Canada
Inborn errors of metabolism are inherited genetic
disorders resulting in faulty enzymatic activities. The metabolic
consequences are accumulation of toxic metabolites prior to the enzymatic
block and frequently lack of essential products of the reaction. Most of
these disorders are of autosomal recessive inheritance. Individually these
diseases are rare, but the overall occurrence is high and constitutes
significant clinical load. The precise diagnosis often requires
sophisticated biochemical analysis.
Gas chromatography-mass spectrometry (GC/MS) is
one of the most powerful techniques for the analysis of complex mixtures
such as body fluids. The first identification of isovaleric academia by
Tanaka in 1966 using GC/MS paved the way for the application of this
technique to the study of organic acidurias. The development of new modes
of ionization and computer assisted data analysis have made it possible to
diagnose metabolic disorders affecting organic acids, amino acids, fatty
acids, bile acids, carbohydrates, steroids, prostaglandins and vitamins. It
has been the most valuable method for diagnosis of metabolic diseases for
over two decades.
Recently developed tandem mass spectrometry (MS/MS)
technique is capable of identifying about 25 metabolic disorders characterized
by the presence of abnormal acylcarnitines and amino acids profiles from a
blood spot specimen in a very short analysis time. It greatly expends
neonatal screening coverage and reduces the false positive rate, thus changing
the screening system from "one test-one disorder" to the
"one test-many disorders" concept. The range and type of relevant
substances measurable by tandem mass spectrometry can also be extended. Mass
spectrometry has made significant contributions and will continue to play a
pivotal role in the advances in our knowledge of inborn errors of
metabolism.