Volume 1, Number 2: Summer Solstice, 1999

Inborn Errors of Metabolism in Adult Patients - BC Diabetes Foundation

Sandra Sirrs MD, FRCPC

UBC Division of Endocrinology University of British Columbia, Vancouver, B.C., Canada

A New Frontier in Internal Medicine


Inborn errors of metabolism (IEM) are genetic conditions which result in an inability of the cells of the body to perform basic functions required for life such as breaking down food, making energy, or disposing of toxic byproducts. There are more than 500 IEM which have been identified and many thousands more which have not yet been described. Although each individual type of IEM is rare, the vast number of potential disorders means that many people are affected by the various types of IEM. For example, in British Columbia, there are almost one thousand known patients with IEM and there are likely many more who have not been diagnosed. One third of the known patients in B.C. are over the age of 18 years.

In the past, most patients with these conditions did not survive to adulthood or, if they did, were so severely disabled from their condition that institutionalization was necessary. Fortunately, the situation is changing for the better. Improved diagnostic techniques and therapies mean that many of these conditions are now amenable to treatment. Therefore, many conditions which were previously considered lethal are now forms of chronic disease. As the knowledge about IEM increases, it has become apparent that many conditions may not present until adulthood, and thus new diagnoses of genetic abnormalities are being made at any age. For these reasons, the population growth of adults with IEM has exploded.

The whole field of inborn errors of metabolism in adult patients is shrouded by a lack of knowledge. As these patients mature, they develop medical conditions common to adults such as high blood pressure, obesity, and diabetes. These common medical conditions can have uncommon manifestations and require novel therapeutic approaches in patients with inborn errors of metabolism. Also, as the patients age, new manifestations of their IEM become apparent. Thus, the care of these individuals is a rapidly evolving and exciting field, with many unique opportunities for research. More importantly, it is critical that these adult patients be looked after by physicians experienced in health-care problems of adults. Just as children are not just “small adults”, so are adults not just “big children”.

Towards a Solution

To meet the needs of this unique patient population, the Adult Metabolic Diseases Clinic (AMDC) was opened April 1, 1999 at Vancouver General Hospital. The AMDC is a provincial service whose mandate is to provide expert medical, nursing, nutritional and educational care for people over the age of 18 years with IEM. Plans for the future include out-reach programs to take place around the province, group educational activities such as low protein cooking classes, establishing support networks by introducing patients with rare conditions to others with similar problems, and education of health care professionals involved in the care of these patients.

Of the many IEM being looked after by the AMDC staff, there are three which I will discuss here.

  1. The most common IEM at our clinic is phenylketonuria (PKU). PKU occurs in about 1/15,000 live births. Untreated, almost all patients with PKU become severely mentally retarded, with IQ’s below 50, but with a normal lifespan. With early dietary intervention, the mean IQ of the patients approaches the normal range. As these patients get older, the issue of pregnancy arises frequently. If women with PKU get pregnant and their metabolic control is poor, there is a greater than 85 percent chance that the baby, who most likely does not have PKU itself, will have severe brain damage and there’s a greatly increased risk of other types of congenital defects that affect the heart and the bowels. Successful dietary therapy which is initiated prior to conception and maintained throughout the pregnancy can reduce the risk of congenital abnormalities to that approaching the risk in the background population.
  2. Homocystinuria is another interesting metabolic disease where the patients lacked an enzyme which normally breaks down an amino acid called homocysteine. The elevated levels of homocysteine that result from this IEM lead to osteoporosis, dislocation of the lens in the eye, and a greatly increased risk of vascular disease such as heart attack, stroke, and blood clots in the legs. Untreated, one-quarter of affected patients have had at least one vascular event by the age of 20. Treatment involves aggressive dietary changes, supplementation with special medical formulas which are low in methionine, and high dose vitamin therapy which can help reduce levels of homocysteine. Although classical homocystinuria is rare, lower grade elevations of homocysteine are being found with increasing frequency in patients who have had heart attacks or strokes at an early age. This is an area of rapidly expanding research and is a special interest of the AMDC staff.
  3. Another group of diseases followed by the clinic involve the urea cycle. The urea cycle normally breaks down nitrogen, which is a component of protein. If the urea cycle does not function normally, patients cannot get rid of excess nitrogen and this results in a buildup of ammonia levels in the body. High levels of ammonia cause swelling in the brain, seizures, and coma which can be fatal. This is a life threatening situation. In adults, the post-partum period and the menopausal period are times when buildup of ammonia levels is common in patients who have defects involving that urea cycle. Many fatalities have been reported in the past in women with these disorders who have had children. It is hoped that, with increasing education of health professionals and the public, that the awareness of these disorders will increase and thus decrease the rate of post-partum fatalities.

The staff of the AMDC are excited to be involved in this new and rapidly expanding field of medicine. For further information about the Adult Metabolic Diseases Clinic, you can contact the clinic by telephone at: 604-875-5965 or by fax at 604-875-8276.

Dr. Sandra Sirrs is the Medical Director of the Adult Metabolic Diseases Clinic and is the program director of the University of British Columbia Division of Endocrinology Fellowship program.

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