Birth Defects Resulting From Single Gene Defects

Categories of Factors Responsible for Birth Defects Abnormalities of Individual Genes (Single Gene Defects) Chromosomal Abnormalities Intrauterine Injury Multifactorial Circumstances

How Genetic Errors Cause Disease  If there are errors in the gene (bases are missing or out of order) then the protein synthesis becomes confused.  This confusion can result in defective protein construction.  The function that was supposed to occur is halted creating pathology.  If there are errors in the gene (bases are missing or out of order) then the protein synthesis becomes confused.  This confusion can result in defective protein construction.  The function that was supposed to occur is halted creating pathology.

Single Gene Disorders  Over 4,000 have been identified  Most are recessive  Examples:  Recessive-- Sickle Cell Anemia, PKU, Tay Sachs, Cystic Fibrosis  Dominant-- Huntington’s Chorea, Marfan’s Syndrome  Sex-linked-- Hemophilia, Color Blindness  Over 4,000 have been identified  Most are recessive  Examples:  Recessive-- Sickle Cell Anemia, PKU, Tay Sachs, Cystic Fibrosis  Dominant-- Huntington’s Chorea, Marfan’s Syndrome  Sex-linked-- Hemophilia, Color Blindness

Parent Status Possible Outcomes Recessive Inheritance One Heterozygous n n n nn nn d dn dn 50% Carrier 0 Expression Both Heterozygous d n n dn nn d dd dn 50% Carrier 25% Expression One Homozygous One Free n n d dn dn 100% Carrier

Dominant Inheritance Parent StatusPossible Outcomes/Dominant Inheritance Either Homozygous n n D Dn Dn All D Dn Dn Offspring One Heterozygous n n n nn nn 50% chance D Dn Dn Both Heterozygous n D n nn Dn 75% chance D Dn DD

Sex Linked Inheritance FemaleParent XnXd Male XXXn Female Free XXd Female Carrier Parent Y XnY Male Free XdY Male Expresses

Categories of Factors Responsible for Birth Defects 1.Abnormalities of Individual Genes (Single Gene Defects) 2.Chromosomal Abnormalities 3.Intrauterine Injury 4.Multifactorial Circumstances

Sickle Cell Anemia  Occurs when the gene that codes for glutamic acid codes wrong and instead codes for valine which doesn’t bind well with O2.  This causes cells to become sickle shaped  Sickle shaped cells do not circulate well and clog capillaries easily  Occurs when the gene that codes for glutamic acid codes wrong and instead codes for valine which doesn’t bind well with O2.  This causes cells to become sickle shaped  Sickle shaped cells do not circulate well and clog capillaries easily

Sickle Cell Anemia  Epidemiology:  8% or 1/12 of African Americans carry the gene  1/400 have sickle cell  A blood test is available to determine if one carries the gene  In utero determination is also available  An example of co-dominance:  both alleles are fully expressed in the heterozygous state  Epidemiology:  8% or 1/12 of African Americans carry the gene  1/400 have sickle cell  A blood test is available to determine if one carries the gene  In utero determination is also available  An example of co-dominance:  both alleles are fully expressed in the heterozygous state

1.Anemia- red cells live only days as opposed to Clotting- loss of blood flow to tissue = pain 3. Infection- due to poor delivery of blood 4. Dactylitis- swelling of hands and feet 5. Physical development- Stunted 6. Lower life expectancy- Males: 42 Females: 48 Sickle Cell Anemia Syndrome

Sickle Cell Anemia Treatment  Rest  Hydration  Analgesia  Transfusion therapy  Prophylactic antibiotics  Oxygen therapy  Rest  Hydration  Analgesia  Transfusion therapy  Prophylactic antibiotics  Oxygen therapy

Cystic Fibrosis  Epidemiology:  Most common lethal genetic disorder in the Caucasian population.  Estimates are that 1/25 people may be carriers  Syndrome:  Defect alters the way epithelial calls transport sodium and chloride ions  Disease targets the lungs and pancreas  Epidemiology:  Most common lethal genetic disorder in the Caucasian population.  Estimates are that 1/25 people may be carriers  Syndrome:  Defect alters the way epithelial calls transport sodium and chloride ions  Disease targets the lungs and pancreas

Cystic fibrosis Syndrome  Respiratory insufficiency  Poor growth  Malnutrition  Life expectancy varies from a few years to the 30’s  Respiratory insufficiency  Poor growth  Malnutrition  Life expectancy varies from a few years to the 30’s

Inborn Errors of Metabolism ENZYMOPATHIES Precursors Enzyme Product A Alternate Route Product B lack of end product precursor accumulation secondary product accumulation loss of feedback inhibition

PKU (Phenylketonuria) Secondary Product Accumulation  Syndrome:  The body cannot breakdown the protein phenylanine.  The infant appears healthy the first year then gradually develops retardation as a result of nervous system damage caused by excess acid in cells.  Epidemiology:  1/14,000 white babies  1/300,000 black babies  Syndrome:  The body cannot breakdown the protein phenylanine.  The infant appears healthy the first year then gradually develops retardation as a result of nervous system damage caused by excess acid in cells.  Epidemiology:  1/14,000 white babies  1/300,000 black babies

PKU Treatment:  Special diet is available in which foods containing phenylalanine are removed thus eliminating secondary product accumulation. Prevention:  A screening test at birth is routine.  This test has proven to be very cost effective.  Special diet is available in which foods containing phenylalanine are removed thus eliminating secondary product accumulation. Treatment:  Special diet is available in which foods containing phenylalanine are removed thus eliminating secondary product accumulation. Prevention:  A screening test at birth is routine.  This test has proven to be very cost effective.  Special diet is available in which foods containing phenylalanine are removed thus eliminating secondary product accumulation.

Tay Sachs Disease  Syndrome:  Hexosaminidase, the enzyme responsible for lipid metabolism is absent  The cells are unable to break down fat  The build up of lipids (ganglioside) occurs in the nerve cells  The child will begin to lose developmental skills at about six months and deteriorate until death by age four.  Prevention:  Screening for carriers of the gene and screening of the fetus.  Syndrome:  Hexosaminidase, the enzyme responsible for lipid metabolism is absent  The cells are unable to break down fat  The build up of lipids (ganglioside) occurs in the nerve cells  The child will begin to lose developmental skills at about six months and deteriorate until death by age four.  Prevention:  Screening for carriers of the gene and screening of the fetus.

1. Albinism- enzyme is missing to produce melanin 2. Familial Hypothyroidism- loss of feedback inhibition 3. Sex-linked / x-linked inheritance- a. Color blindness b. Hemophilia Other In-Born Errors of Metabolism

Categories of Factors Responsible for Birth Defects Abnormalities of Individual Genes (Single Gene Defects) Sickle Cell Anemia Cystic Fibrosis Phenylketonuria Tay Sachs Disease Albinism Familial Hypothyroidism Hemophilia