Clinical trials examining treatments for inborn errors of amino acid metabolism

Abstract

ABSTRACTIntroduction: More than half a century ago, phenylketonuria (PKU) became the first treatable inborn error of metabolism identified through newborn screening, ushering in a new era of metabolic medicine. Since that time, the underlying cause of numerous other inborn errors have been elucidated and added to newborn screening panels. Therapy for most amino acidopathies was initially dietary, including PKU, which remains the prototype for this group of disorders and a model for other inborn errors of metabolism (IEMs). However, in addition to dietary management, pharmacological intervention and organ transplantation have emerged as mainstays of treatment for several others of the inborn errors of metabolism.Areas covered: This article reviews the clinical trials and evolving therapies for inborn errors of metabolism, including the aminoaciopathies: phenylketonuria, tyrosinemia, maple syrup urine disease, non-ketotic hyperglycinemia, classical homocystinuria; the organic acidurias: propionic academia, methylmalonic acidemia, cobalamin disorders, isovaleric academia, glutaric acidemia type I (GA1), pyridoxine dependent epilepsy; and urea cycle defects.Expert opinion: Despite our broadening knowledge, there have been very few randomized, double-blinded clinical trials due to the rare nature of these disorders, as well as the associated high morbidity and mortality associated with the untreated natural history.