In general when people think of a genetic defect or an inborn error of metabolism (IEM), they think in terms of disorders that are diagnosed and treated in infancy or early childhood. Interestingly, the more we learn about IEM, the more we see that IEM can be diagnosed at nearly any age. Milder forms of the disorders may present in later years, anywhere from adolescence through adulthood.
Classical presentations of IEM are generally due to total or near total enzyme deficiencies that result in life-threatening medical crises, or major developmental delay and mental retardation. Adults or near adults who present with a range of milder symptoms may be misdiagnosed or nor diagnosed at all.
A few examples of IEM that may have later and milder presentations include:
1) Ornithine transcarbamylase (OTC ) deficiency, the most common urea cycle defect which is often fatal in newborn male infants, can and does present in the teenage years as altered mental status, when a protein load cannot be handled and ammonia levels rise and impact brain function.
2) Carnitine palmitoyltransferase 2 (CPT2) deficiency, a disorder of fatty acid metabolism, presents with cardiomyopathy and liver failure in the newborn period. It can also present with muscle weakness, myopathy and rhabdomyolysis in the teenage or young adult years when the teenager tries out for a sports team and the muscle cannot metabolize adequate fats.
3) 3-methylcrotonyl-CoA carboxylase (3MCC) deficiency, a disorder of leucine metabolism, may present in infants or toddlers as feeding difficulties, neurological symptoms including seizures, and can cause death. 3MCC can also present in a completely asymptomatic mother whose infant is picked up on newborn screening because of the Mom’s abnormal metabolites in the infant’s blood.
In most of these cases the deficiency is mild enough that the individual is self-regulating, avoiding foods or activities that make them feel bad. In addition, the IEM may not manifest unless some other confounding factor precipitates it, such as stress, illness, or fasting. The important thing to remember though, is that altered mental status in a teenager does not always represent alcohol, drug or other mood altering substances. IEM can be diagnosed at any age and should always be considered as part of the differential diagnosis.
-Patti Jones PhD, DABCC, FACB, is the Clinical Director of the Chemistry and Metabolic Disease Laboratories at Children’s Medical Center in Dallas, TX and a Professor of Pathology at University of Texas Southwestern Medical Center in Dallas.