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Abstract
Inborn errors of metabolism (IEMs) or metabolic disorders are complex conditions involving abnormalities in biochemical and metabolic pathways necessary for healthy human existence. They are often caused by partial or total deficiency of key enzymes and these conditions usually present in infancy or early childhood. Some may not be identified until adolescence or even during the adult years. This discussion reviews some of the IEMs that can become evident in the adolescent years, such as adrenoleukodystrophy, glycogen storage diseases, lysosomal storage diseases, urea cycle disorders, and others. Management focuses on symptomatic treatment and when available as well as affordable, enzyme replacement therapies. Gene therapy and stem cell transplantation are options under current research in addition to finding more replacement enzymes.
Keywords: Pediatrics, inborn errors of metabolism, metabolic disorders
Introduction
Inborn errors of metabolism (IEMs) or metabolic disorders are unusual, complex conditions involving abnormalities in biochemical and metabolic pathways necessary for human life. Though often identified in infancy or childhood, some may not be diagnosed until adolescence or adulthood. The initial term, inborn errors of metabolism, was introduced by Sir Archibald Garrod (1857-1936) in 1902 and referred to cystinuria, albinism, alkaptonuria, and benign pentosuria (1). Phenylketonuria (PKU) was identified in 1934 by Ivar Asbjørn Følling (1888-1973) and in the second half of the 20st century, over 500 IEMs have been identified (2). Table 1 presents a partial list of IEMs (2).
IEMs are complex conditions that are usually genetic, typically inherited in an autosomal recessive manner, though a few are X-linked recessive conditions (i.e., Fabry disease, ornithine carbamylase deficiency, or pyruvate dehydrogenase deficiency). Autosomal dominance is noted in Marfan syndrome, familial hypercholesterolemia, and acute intermittent porphyria. Some IEMs are caused by mitochondrial genome mutations and there can be enzyme deficiencies or problems with cellular transporters. Most IEMs may be classified in two general categories:
* Diseases that lead to intoxication due to accumulation of toxic compounds (typically there is an asymptomatic interval until ingestion of a substrate leads to accumulation of toxic metabolites proximal to the dysfunctional or absent enzyme)
* Diseases that lead to deficient energy production, such as disorders of glycolgenolysis or gluconeogenesis, among others. Peroxisomal and lysosomal storage disorders may have features not associated with ingestion of substrates. These are usually...