Academy of Diagnostics & Laboratory Medicine - Scientific Short

Inborn errors of metabolism

Are they just for kids?

Michael J. Bennett

A 72 year old female was recently referred to a metabolism clinic (yes at a children’s hospital!) with a very long history of anemia and bone pain that had been monitored but not particularly investigated by numerous internists. She was subsequently found to be deficient in the enzyme glucocerobrosidase and to have the non-neuronopathic form of Gaucher disease. These signs and symptoms could have been alleviated with enzyme replacement therapy much sooner if a diagnosis had been made earlier.

A 21 year old male police recruit tries out for enrollment into a SWAT squad. In the process of intensive training (boot camp), he develops severe muscle cramps leading to “blood” in the urine, frank clinical rhabdomyolysis and acute life-threatening renal failure. He survived and is subsequently shown to have carnitine palmitoyltransferase 2 deficiency, a defect of energy metabolism for which high impact muscular activity is contra-indicated.

Most of us are taught that inborn errors of metabolism, or metabolic diseases, form a domain that is unique to the investigation of newborns, infants and children. My early education in this field was exactly that. As a result it is not surprising that most metabolic disease diagnostic laboratories, including my own, are based in children’s hospitals or built to serve pediatric populations. As our experience in this field expands, we are increasingly becoming aware of adult presentations of the same metabolic diseases and a need for expansion of services beyond our historical boundaries.

The initial text book cases of most metabolic diseases were based on the most severe presentations of metabolic acidosis, hypoglycemia, hyperammonemia or neurodegeneration. Many cases died early with intractable metabolic derangement. These cases served as the basis of our early understanding of metabolic diseases, of their severity and of the acute needs for management.

However, this pattern is changing on two separate fronts: firstly; newborn screening is identifying a number of metabolic diseases presymptomatically. Early diagnosis coupled to improved patient management is starting to significantly reduce the numbers of metabolic crises that these patients and their attending physicians endure. Survival is frequently much longer today and many patients with metabolic diseases are now reaching adulthood. With that comes the additional burden of adult-related diseases such as hypertension, heart disease and diabetes that were not issues that had to be dealt with previously by metabolic specialists and few adult internists who deal with these additional complications are trained to deal with complications of metabolic diseases . Secondly; we now recognize that there is a complete spectrum of disease severity for most if not all metabolic diseases that include both the severe forms and milder forms that can present later in life as illustrated by the cases above. These milder cases may not all be detected by newborn screening or the disease may not be included in screening programs. Many of these late presenting patients are unlikely to be seen initially by a specialist in metabolism, if at all, when they do finally present clinically adding delay to the final diagnosis if it is ever made.

When I first started working in a children’s hospital it was always easy to differentiate patients from parents but as we start to see increasing numbers of older individuals with metabolic disease that distinction is getting blurred as many of the “parents” we see today are actually patients.

Do others see the same in their practice?

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Academy of Diagnostics & Laboratory Medicine Designation

Fellows of the Academy use the designation of FADLM. This designation is equivalent to FACB and FAACC, the previous designations used by fellows of the National Academy of Clinical Biochemistry and AACC Academy. Those groups were rebranded as Academy of Diagnostics & Laboratory Medicine in 2023.