A clinical approach to inherited metabolic diseases

Abstract

Inborn errors of metabolism (IEM) are individually rare, but collectively numerous. The recent application of tandem mass spectrometry (tandem MS) to newborn screening and prenatal diagnosis has enabled presymptomatic diagnosis for some IEM. However, for most, neonatal screening tests are either too slow, expensive or unreliable and, as a consequence, a simple method of clinical screening is mandatory before initiating sophisticated biochemical investigations. The clinical diagnosis of IEM relies upon a limited number of principles: To consider IEM in parallel with other more common conditions; for example, sepsis or anoxicischemic encephalopathy in neonates, and intoxication, encephalitis and brain tumors in older patients. To be aware of symptoms that persist and remain unexplained after the initial treatment and the usual investigations have been performed. To suspect that any neonatal death may possibly be due to an IEM, particularly those that have been attributed to sepsis. To carefully review all autopsy findings. Not to confuse a symptom (such as peripheral neuropathy, retinitis pigmentosa, cardiomyopathy, etc.) or a syndrome (such as Reye syndrome, Leigh syndrome, sudden infant death, etc.) with etiology. To remember that an IEM can present at any age, from fetal life to old age. To know that although most genetic metabolic errors are hereditary and transmitted as recessive disorders, the majority of individual cases appear sporadic because of the small size of sibships in developed countries. To initially consider inborn errors which are amenable to treatment (mainly those that cause intoxication). In the acute, emergency situation, to undertake only those few investigations that are able to diagnose treatable IEM. To obtain help from specialized centers. Based mainly upon personal experience over 40 years, this chapter gives an overview of clinical clues to the diagnosis of inborn errors of metabolism in pediatrics and adulthood. In the following pages, inborn errors amenable to treatment are printed in bold.