Global Study Examines Toll of Genetic Defects

By David Brown
Washington Post Staff Writer
Tuesday, January 31, 2006

About 6 percent of children worldwide -- nearly 8 million babies a year -- are born with a physical or mental disability caused by a genetic defect, according to the first comprehensive estimate of the global toll.

Each year, about 3.3 million of them die before their fifth birthday, victims of what the report's authors call a "serious and vastly unappreciated public health problem."

Although parents everywhere face some risk of having a child with a defect, the risk is much greater in poor and middle-income countries. Reasons include inadequate maternal health and prenatal care, more intermarriage, and a higher frequency of some disease-causing genes.

The experience in rich countries over the past quarter-century, however, suggests that 70 percent of these defects can be prevented or lessened.

The authors of the report, which was sponsored by the March of Dimes, hope it will be the first step in convincing countries that birth defects are neither inevitable nor untreatable.

"We hope researchers and others will go to their health ministries and say, 'Here are the data; we have a problem,' " said Christopher P. Howson, an epidemiologist at the March of Dimes.

Interventions proven to work include genetic counseling for sickle cell anemia, prenatal diagnosis of Down syndrome, supplementing folic acid in the diet to reduce the risk of neural tube defects, newborn screening for some rare metabolic disorders such as phenylketonuria, and surgical repair of heart defects. Most of those strategies are unavailable in low-income countries.

"Birth defects are a really still pond," Howson said. "We hope this report will be like a rock dropped into that pond that creates changes in policy and action."

The data come from many sources.

Industrialized countries have registries that compile statistics on birth defects, but many lower-income countries do not. For them, the authors used data from research studies, statistics from neighboring countries, and estimates based on known facts, such as the prevalence of the sickle cell genetic mutation in a population.

There are about 7,000 known defects caused by genetic errors. The researchers estimated that in 2001, about one-quarter of the defects were of five common types -- heart malformations, defects of the neural tube that develops into the brain and spinal cord, disorders of hemoglobin, the oxygen-carrying protein in blood, Down syndrome, and an enzyme disorder called G6PD deficiency.

The 85-page report does not include defects caused by damage to the fetus during pregnancy, primarily from exposure to alcohol, iodine deficiency in the mother, rubella (German measles) infection and syphilis. Those statistics are even harder to obtain.

The rate of defects per 1,000 births ranges from 82 in Sudan and 81 in Saudi Arabia at the high end, to 40 in France and 42 in Austria. The United States has the 20th-lowest rate, with 48.

Affluence is a big determinant of the risk. In low-income countries, the average rate is 64; in middle-income countries, 56; and in rich countries, 47.

Within those categories, however, there are widely divergent rates because of differences in culture and biology. For example, one reason that low-income Sudan and middle-income Saudi Arabia are at the top of the list is the high frequency of marriage between cousins.

Inbreeding produces a high rate of "recessive single-gene disorders," which arise when both the mother and father give their child the same rare gene. That is unlikely to happen unless the parents are related, or at least members of the same small ethnic group. Worldwide, the rate of such disorders is seven per 1,000 life births. In Sudan it is 26, and in Saudi Arabia it is 23.

Similarly, hemoglobin disorders such as sickle cell anemia and thalassemia are much more common in places where malaria was prevalent over the eons. The mutations that cause those ailments provide some protection against malaria when a person inherits only a single copy of the mutated gene, but inheriting two copies, one from each parent, results in disease.

Today, the rate of hemoglobin defects is 23 per 1,000 births in Benin in West Africa, a region of intense malaria transmission. The rate is a relatively high 2.3 per 1,000 in Greece, a country that has eliminated malaria but whose population still carries the protective thalassemia mutation at a high frequency.

The authors of the report hope it will spur countries to realize they can do something about birth defects. One of them, Arnold Christianson, said an effort is underway in his country, South Africa.

A recent survey there revealed that 70 percent of women older than 35 who go to clinics early in pregnancy are not asked their age or told they are at an increased risk of having a baby with Down syndrome, a chromosomal disorder that causes mental retardation.

Although most Down children have characteristic facial features, in a rural area outside Johannesburg, only 16 percent received diagnoses at birth, and only 50 percent by 6 months. And practitioners who did suspect the defect were often wrong. Of the babies sent for testing, 32 percent did not have the disorder, said Christianson, a geneticist at the University of Witwatersrand in Johannesburg.

With the help of a grant from the March of Dimes, he and his colleagues are developing a course to teach nurses and birth attendants the rudiments of medical genetics and how to examine newborns for common birth defects, including Down syndrome.

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