Inherited Metabolic Disorders: Aspects of Chronic Nutrition Management

Abstract

The introduction of newborn screening and the development of new therapies have led to an expanding population of patients with inherited metabolic disorders, and these patients are now entering adulthood. Dietary therapy is the mainstay of treatment for many of these disorders, and thus, trained metabolic dietitians are critical members of the multidisciplinary team required for management of such patients. The main goals of dietary therapy in inborn errors of metabolism are the maintenance of normal growth and development while limiting offending metabolites and providing deficient products. Typically, the offending metabolite is either significantly reduced or removed completely from the diet and then reintroduced in small quantities until blood levels are within the normal range. Such treatment is required in infancy, childhood, and adulthood and requires careful monitoring of micronutrient and macronutrient intake throughout the life span. The goal of this review is to highlight the basic principles of chronic nutrition management of the inborn errors of protein, carbohydrate, and fat metabolism.

Keywords: diet therapy; inborn errors of metabolism; metabolic diseases; metabolic disorder; nutrition therapy.

Figure 1

Principles of nutritional management of inborn errors of metabolism. A. A model metabolic pathway is depicted in an unaffected individual with metabolites labeled with letters and enzymes numbered. B. In an individual in which enzyme 2 is deficient, product B will accumulate and products C and D will become deficient. To treat this patient, products A and B will be limited in the diet, and products C and D may need to be supplemented in the diet. In addition, excretion of product B may be enhanced, if possible. Cofactors of enzyme 2, if they exist, may be supplemented depending on the disorder to enhance enzyme activity.

Figure 2

Phenylalanine hydroxylase enzyme activity is deficient in phenylketonuria (PKU). As a result of this enzyme deficiency, phenylalanine accumulates and tyrosine becomes deficient. Thus, consumption of phenylalanine must be limited and tyrosine supplemented in patients with PKU.

Figure 3

Urea Cycle Disorders. Enzymes associated with particular urea cycle disorders include NAGS (n-acetylglutamate synthase), CPS (carbamoyl phosphate synthetase I), OTC (ornithine transcarbamylase), ASS (argininosuccinate synthetase), ASL (argininosuccinate lyase), and ARG (arginase I).