9Diagnosis and management of inherited aminoacidopathies in the newborn and the unborn

Abstract

Disorders of amino acid metabolism have played a prominent role in the evolution of our concepts of inherited metabolic diseases since the inception of this field. Three of the four disorders which led Archibald Garrod (1908) to his seminal concepts of 'inborn errors of metabolism' involved amino acids (alcaptonuria, cystinuria, and albinism). Another aminoacidopathy, phenylketonuria, claims historical import for several reasons: it was the second inborn error for which a specific enzymatic deficiency was identified in vitro; it was the first disease for which mass neonatal screening was ordered by law; and it was the first enzymopathy documented to respond to specific dietary restriction. During the past thirty years, more than 80 different disorders of amino acid transport and catabolism have been described, and the logarithmic increase in newly recognised conditions continues (Scriver and Rosenberg, 1973). Individually, each of the aminoacidopathies is rare, but collectively they affect about 1/1000 humans in whom they cause a very considerable morbidity and mortality (Levy, Shih and MacCready, 1972). The inherited aminoacidopathies provide a glimpse of the richness of the fabric of human mutations, or 'nature's experiments'. Mass screening for disorders such as PKU and homocystinuria which cause delayed clinical manifestations will not be discussed in this chapter as it is dealt with elsewhere in this volume (see page 153 ff.) and also because this matter has been reviewed extensively in the past (Scriver and Rosenberg, 1973); nor will the harmless aminoacidopathies (i.e., iminoglycinuria, cystathioninuria) be considered. Rather, it is the signs, symptoms, diagnostic approach, and management of children with those disorders of amino acid metabolism which lead to acute, life-threatening consequences in the first days or weeks of life which will be surveyed. For specific details of individual disorders, the reader is referred to recent articles, chapters or books by O'Brien and Goodman (1970), Frimpter (1973), Scriver and Rosenberg (1973) and Rosenberg and Scriver (1974).