Inborn errors of metabolism are inherited disorders that are caused by a defect in a single gene. There are many inborn errors of metabolism. Some produce relatively unimportant physical features or skeletal abnormalities. Others produce serious disease and even death.
The gene defect can cause a particular enzyme to be defective or missing. Because the enzyme fails to do what it is supposed to do for the body, a variety of health conditions may result.
Enzymes help the body by stimulating biological reactions inside cells, thus making it possible for the body to use food, produce energy, and do work. When a particular enzyme is defective or missing, then the body is unable to do something that it should do to maintain health. The enzyme involved determines what the body cannot do and what the resulting physical features are. Inborn errors of metabolism affect about 1 in every 5,000 babies born. Some of the more familiar inborn errors of metabolism are phenylketonuria (PKU), sickle cell anemia, and Hunter Syndrome.
The symptoms of inborn errors of metabolism vary greatly. Each one must be reviewed separately to know what the physical features are. Often, an infant will show signs of failure to thrive by failing to gain weight, not eating well, and generally showing developmental delay. Vomiting and diarrhea are among other symptoms that may signal the healthcare professional to test for an inborn error of metabolism.
The enzyme defects that lead to the inborn errors of metabolism are caused by abnormal genes. In most cases, the abnormal gene is autosomal recessive in character. Autosomal means that the gene is on one of the twenty-two non-sex chromosomes. Recessive means that there must be two copies of the gene, one inherited from each parent, in order for the enzyme defect to exist.
It is not possible to generalize about the nature of the enzyme defects or their locations on the chromosomes. Defects have been observed in virtually all biological reactions, and the responsible genes are scattered among the chromosomes. In many cases, the structure of the gene is known. More often, the chemicals in the body that are affected by the inborn error can be identified.
It is not known precisely how many people are affected by the various inborn errors of metabolism. Hundreds of such errors have been described in the medical literature, and record keeping has not been precise for most of them.
The enzyme defects that lead to the inborn errors of metabolism are caused by genetic abnormalities present from the time of conception. Therefore, nothing can be done to prevent them. The diseases caused by the inborn errors, however, may be preventable in some cases. A familiar example of this is PKU, in which the toxic buildup of phenylalanine in the body, occurring because of the missing enzyme, can be averted by withholding phenylalanine from the diet.
Another way to prevent the diseases caused by the inborn errors of metabolism is by genetic counseling and family planning. A couple who know that they are both carriers of a gene responsible for an inborn error may, for instance, choose not to have children at all.
Physical features such as malformations of the skeleton or abnormal hair usually suggest the presence of an inborn error of metabolism. Whether or not the physical features are obvious, diagnosis is confirmed by checking the blood or urine for one or more of the compounds involved. Tests for urine amino acids can be helpful. There may be too much of a compound, not enough of another, or abnormalities among others. The compounds may also be studied in tissue from biopsies. DNA tests may also confirm the diagnosis.
Each inborn error of metabolism has its own pattern of long-term effects.
Parents who have had one child with an inborn error of metabolism are at risk to have other affected children. One in 4 pregnancies of such couples is expected to result in an affected child. People with an inborn error of metabolism pass on an abnormal gene to their children. The children will not be affected, however, unless both partners also carry a single copy or 2 copies of the gene.
Some inborn errors of metabolism are more often found in certain racial and ethnic groups. The children of women with some inborn errors of metabolism are at risk because of an unfavorable environment in the womb.
Many of the inborn errors of metabolism can be treated effectively. Treatment depends on the enzyme defect itself and how readily the compounds involved can be eliminated or replaced.
Side effects of treatment depend on the enzyme defect being treated.
Treatment may need to continue as long as the enzyme defect continues, often for life.
Most inborn errors of metabolism are monitored by routine blood or urine tests.
Roberts JAF and Pembrey ME: An Introduction to Medical Genetics. Oxford University Press, 1985.
Stevenson RE, Hall JG, and Goodman RM: Human Malformations and Related Anomalies. Oxford University Press, 1990.
[hyperLink url="http://www.emedicine.com" linkTitle="www.emedicine.com"]www.emedicine.com[/hyperLink]