ABSTRACT
Disorders of fatty oxidation display two general types of presentation. The first, hypoketotic hypoglycemia, is the clinical picture of Reye syndrome. In fact, it is now clear that most patients who appear to have Reye syndrome have an inborn error of metabolism, the most common being MCAD deficiency and ornithine transcarbamylase deficiency (Chapter 29) [2,3]. The other presentation reflects the chronic disruption of muscle function with symptoms relevant to myopathy or cardiomyopathy, including weakness, hypotonia, congestive heart failure, or arrhythmia. Both types of presentations may be seen in the same family or even in the same individual. Another presentation is with the sudden infant death syndrome (SIDS) [4-7]. We and others have been able to make retrospective diagnoses of MCAD in infants who had died of SIDS by retrieval of neonatal screening blood spots after making the diagnosis of MCAD deficiency in a subsequent sibling and assay for the common mutation in the DNA or for octanoylcarnitine. The introduction of the
Fatty acid oxidation
H2O
R C
O
S CoA
C
O
S CoA
C
O
S CoA
C
O
S CoA
RC
O
S CoA
R
H OH
C
FAD
NAD
H NADH
Enoyl CoA hydratase
3-Hydroxyacyl CoA dehydrogenase
3-Ketoacetyl CoA thiolase Acetyl CoA
CoA-SH
R
C
O
Acyl CoA dehydrogenase FADH2
R
tandem mass spectrometric analysis of acylcarnitines has greatly facilitated the diagnosis of this and other disorders of fatty acid oxidation, and its application to the screening of newborns is a major addition to preventive medicine. This should prevent further examples of SIDS due to MCAD deficiency.
