In addition to the investigation of symptomatic individuals, the array of available genetic and biochemical tests has made practical the mass screening of newborns for inborn metabolic defects. Innovative tests have also led to the discovery of a number of previously unknown diseases and have clarified the basic biochemistry of old ones. As a consequence, the neurologist’s role is changing. No longer must we wait until a disease of the nervous system has declared itself by conventional symptoms and signs, by which time the underlying lesion may have become irreversible. Now it is possible to find patients who, although asymptomatic, are at risk and to introduce dietary and other measures that may prevent injury to the nervous system. This is especially important to families who have already had an affected infant. To assume this new responsibility intelligently requires knowledge of genetics, biochemical screening methods, and public health measures.
The many clinical syndromes by which these inborn errors of metabolism declare themselves vary in accordance with the nature of the biochemical defect and the stage of maturation of the nervous system at which these metabolic alterations become apparent. In phenylketonuria, for example, there is a specific effect on the cerebral white matter, mainly during the period of active myelination; once the stages of myelinogenesis are complete as detailed in Chap. 27, the biochemical abnormality becomes relatively harmless. Even more important from the neurologist’s point of view is the level of function that has been achieved by the developing nervous system when the disease strikes. A derangement of function in a neonate or infant, in whom much of the cerebrum is not fully developed, is much less obvious than one in an older child. Moreover, as the disease evolves, the clinical manifestations are always influenced by the ongoing maturation of the untouched elements in the nervous system. These interactions may give the impression of regression of attained neurologic function, lack of progress of development (developmental delay), or even improvement in function that is attributable to continuing maturation of the normal parts of the nervous system.
Because of the overriding importance of the age factor and the tendency of certain pathologic processes to appear in particular epochs of life, it has seemed to the authors logical to group the inherited metabolic diseases not according to their major syndromes of expression, as we have done in other parts of the book, but in relation to the periods of life at which they are most likely to be encountered: the neonatal period, infancy (1 to 12 months), early childhood (1 to 4 years), late childhood, adolescence, and adult life. Only in the last two age periods do we return to the more clinically useful syndromic ordering of diseases.
In adopting this chronological subdivision, we realize that certain hereditary metabolic defects that most typically manifest themselves at a particular period in life are not necessarily confined to that epoch and may appear, sometimes in variant form, at a later age. Such variations are noted at appropriate points in the discussion.
A small number of progressive metabolic diseases become evident in the first few days of life. The importance of these diseases relates not to their frequency (they constitute only a small fraction of diseases that compromise nervous system function in the neonate) but to the fact that they must be recognized promptly if the infant is to be prevented from dying or from suffering a lifelong severe developmental delay. This inherent threat introduces an element of urgency into neonatal neurology. Recognition of these diseases is also important for purposes of family and prenatal testing.