Genetic Disorders

Recessive genetic disorders (RGD) result from inheriting two defective recessive alleles of a gene, one from each parent. RGD often require careful molecular or biochemical genetic analyses to determine carrier status. Hence, the birth of a child with a recessive disorder may surprise unknowing parents. The probability of two carrier or heterozygous parents having an affected child is 25% each time they conceive. The chance that they will have a heterozygous (carrier) child is 50% for each conception. And the chance of having an unaffected homozygous child is also 25% for each pregnancy. More than 1,000 RGDs have been identified and include: cystic fibrosis, phenylketonuria (PKU), galactosemia, retinoblastoma (Rb), albinism, sickle-cell anemia, thalassemia, Tay-Sachs disease, autism, growth hormone deficiency, adenosine deaminase deficiency, and Werner's syndrome (juvenile muscular dystrophy).

A number of eye disorders are RGDs and are often associated with a mutant gene on chromosome 13. The Retinoblastoma (Rb) gene was the first human gene found to cause cancer and the first human cancer gene in which its location on a chromosome was determined. Rb is a gene that can cause a tumor in the retina, called a retinoblastoma. Most retinoblastomas are inherited; however, in some cases, inheriting a mutation on one allele combined with a spontaneous mutation on the other allele can result in retinoblastoma. Environmental carcinogens (cancer causing agents) can induce a spontaneous mutation. Other recessive eye disorders include myopia (nearsightedness), albinism, day blindness, displaced pupils, and dry eyes.

Some RGDs affect people having a particular ethnic background. For example, cystic fibrosis (CF), sicklecell anemia (SCA), and Tay-Sachs disease (TSD) all have specific mutations in the gene that causes each disorder that are preferentially found in individuals of a certain ethnic background. CF is a common autosomal recessive disease in individuals of Northern European decent and one in every 25 people in this population are carriers. SCA usually is most common in black and Hispanic Down syndrome is a congenital disorder resulting from trisomy (three chromosomes instead of two) in pair 21. Custom Medical Photo. Reproduced by permission.
populations; however, some mutations in the gene that causes SCA are also found in Italian, Greek, Arabian, Maltese, Southern Asian, and Turkish populations. About 1 in 12 blacks are carriers for SCA gene mutations in one of the two hemoglobin genes. Hemoglobin carries oxygen in red blood cells to tissues and organs throughout the body. SCA patients have red blood cells that live only a fraction of the normal life span of 120 days. The abnormal blood cells have a sickled appearance and cannot transport oxygen efficiently. TSD gene mutation carriers are commonly found in Ashkenazi Jewish populations and approximately 1 in 30 are carriers of a mutation.

Galactosemia and PKU are examples of metabolic RGDs and are commonly called biochemical disorders. Both these disorders result from mutations in two different genes, both of which produce dysfunctional enzymes that are important in metabolism. Enzymes speed up chemical reactions and are essential for many cellular processes. People with galactosemia are enzyme deficient for Galactose-1-phosphate uridyl transferase, without which they can not metabolize galactose, a sugar found in milk. If milk and other galactose-containing food items are consumed, these individual cannot digest this compound properly and the result is severe developmental delay. Individuals that inherit PKU are deficient in the enzyme Phenylalanine hydroxylase, which is responsible for converting phenylalanine (an amino acid, a building block of protein) to tyrosine. The build-up of phenylalanine leads to severe developmental delay, and preventing clinical manifestations can be achieved by dietary modification. A phenylalanine-free diet containing sufficient amino acids is available for people diagnosed with PKU. Both of these metabolic disorders result from mutations in two different genes. Carriers are detected through a nationwide newborn screening programs, which differ in testing services from state to state.

Adenoside deaminase deficiency another autosomal recessive genetic disorder that is also called severe combined immunodeficiency. It is caused by a single mutation on chromosome 20 in a gene that encodes an enzyme important for proper functioning of the immune system. Adenosine deaminase converts breaksdown a small molecule called adenosine. Gene therapy has been successful in delivering a normal gene and prevents the damaging effects of adenosine on specific cells important for immune system function.