Monogenic inborn errors of metabolism are a set of disorders inherited in Mendelian fashion, usually as mutant homozygotes for autosomal recessive alleles or as mutant hemizygotes for X-linked alleles. It is their nature to express themselves first in the newborn period or early infancy. Hence, these diseases attract the attention of pediatricians. Accordingly, diagnosis and treatment have been part of pediatric medicine up to now.
Cohorts of these pediatric patients are now reaching adolescence and adulthood. The needs for continued metabolic control and care, with rare exceptions, continue as these patients enter the arena of adult-age medicine. Until now, the challenge to that professional community has been little recognized. The transition for these patients from pediatric medicine to adult medicine is an important concern in genetic medicine.
There is a further challenge. Certain rare hereditary metabolic diseases, masking as common diseases (e.g., coronary artery disease, deep venous thrombosis), may first be recognized only in adulthood. Such disorders, not always clearly recognizable as Mendelian traits, are becoming harbingers for diagnosis, treatment, and counseling of patient and family. These conditions, designated here as hereditary metabolic diseases, can be monogenic, oligogenic, or complex in their patterns of inheritance. This reality raises a question: Is there a need for a specialty of metabolic medicine in adult medicine, as there has been in pediatric medicine? These and other issues will be addressed in this update, which is adapted from the author’s more comprehensive viewpoints (Lee, 2002).
Chapter 5 describes treatment of hereditary metabolic and other genetic diseases. This update examines issues facing adult patients from patient-related and professional points of view. The views expressed reflect the author’s work in the longest-established unit in the United Kingdom dedicated solely to the care of adolescents and adults with hereditary metabolic disease. [The Adult IEM Clinic at University College London: The unit within which the author currently works was first established by Charles Dent in the 1940s. Dent was a clinician-scientist who introduced amino acid chromatography into the clinical setting. This allowed him to diagnose conditions such as arginosuccinic aciduria and maple syrup urine disease (MSUD) in patients with neurologic problems. He was particularly interested in calcium and magnesium metabolism and renal tubular function. The eponymous Dent’s disease describes renal tubular acidosis associated with nephrocalcinosis due to a defect in a chloride channel within the proximal renal tubule (Lloyd et al, 1997). He was the first physician to treat successfully a newborn infant with MSUD in the late 1950s (Dent, Westall, 1961) and indeed was the first to recognize the clinical syndrome of maternal phenylketonuria (Dent, 1957). For the last quarter of the twentieth century, the service was run by Dr. David Brenton, who had a particular interest in homocystinuria and maternal phenylketonuria. Over 25% of the pregnancies that were entered into the United Kingdom PKU register were ...