Download Human Autosomal Recessive Disorders

Human Autosomal Recessive Disorders
1. Cystic fibrosis
What is CF?
 chronic, progressive, frequently fatal disorder of the body’s mucous glands
 primarily affects the digestive and respiratory systems of children and young
adults
 sweat glands and reproductive system also usually affected
 average life span is now about 30 years
How common is CF?
 about 30,000 Americans afflicted with CF
 about 2,500 babies born each year in the U.S. with CF
 more common in whites of northern European descent
 about 1 in 20 whites in the U.S. is a carrier of the recessive CF allele (This
comes to about 12 million people.)
What are the symptoms of CF?
 great variability from individual to individual
 loss of excessive amounts of salt in the sweat
 thick mucous produced in respiratory system and digestive system
o tubes which carry digestive enzymes to small intestine clog
o malnutrition, poor growth, and foul smelling stool can result
o frequent respiratory infections, difficulty breathing, and damage to the
lungs results
o lung damage is the most usual cause of death
What treatment is available?
 special diets and enzymes to manage digestive problems
 antibiotic therapy
 mucous-clearing techniques from the lungs
o drainage accomplished by holding the body in various positions
o chest and back claps and vibration
o exercise is used to help break-up the mucous
o variety of aerosolized medicines now available to clear mucous and open
breathing tubes
What is the cause of CF?
 inability to manage Cl- (chloride) ions especially by epithelial cells
 the first gene for CF found in 1985 on chromosome #7
 this gene accounts for 70% of CF cases
 test for presence of CF allele readily available
2. PKU (phenylketonuria)
What is PKU? What is the cause of PKU?
 Cells possess a faulty enzyme necessary for the metabolism of the amino acid
phenylalanine
 Normally, this enzyme converts excess phenylalanine into another amino acid
known as tyrosine
 As a result, phenylalanine levels build up to dangerous levels
 In particular, this build up affects cells of the central nervous system (brain and
spinal cord)
How common is PKU?
 Refer to the chart below:
Group
PKU cases/live births
Carrier rate
Turks
1/2,600
1/26
Irish
1/4,500
1/33
Caucasian
1/10,000
1/50
African
1/100,000?
?
Jewish
1/200,000
1/225
What are the symptoms of PKU?
 Children with PKU are normal at birth
 However, with time increasing levels of Phe are toxic to the brain
 If left untreated, vomiting, irritability, seizures, and behavioral problems develop
 By 1 year of age, obvious signs of developmental delay are noticed
 If untreated, eventually leads to severe mental retardation, slow growth rate, and
an early death
 Because tyrosine is needed for the body to produce melanin (tanning pigment),
PKU patients tend to have lighter hair, eye, and skin coloration, even if they have
genes for darker pigmentation
What treatment is available?
 All babies in the U.S. and Canada by law are tested for PKU during the first few
days after birth
 Treatment involves a controlled, restricted diet
 The idea is to limit the intake of phenylalanine by reducing high protein foods
(meat, eggs, nuts, dairy, fish)
 Artificial sweeteners (Equal, NutraSweet) possess high levels of phenylalanine
as well (Check the side of a Diet Coke can)
 Diet should be continued throughout life
3. Sickle Cell Anemia
What is sickle cell anemia? What is the cause of sickle cell anemia?
 Chronic blood disease
 Red blood cells become crescent-shaped and do not function normally
 “Sickled” rbc’s are unable to deliver oxygen adequately to body tissues
 A single mutation occurs in the gene which codes for hemoglobin
 The protein hemoglobin fills rbc’s and is responsible for “grabbing” oxygen and
delivering it to all body tissues
 The “bad” hemoglobin causes the entire rbc to buckle from its normal disk shape
into the crescent, sickle shape
 Because the hemoglobin cannot do its job well, the bloodstream has low oxygen
levels and increased acidity – promoting the sickling of rbc’s
 Additionally, because of odd rbc shape, cells tend to get caught in small blood
vessels leading to inappropriate clotting
How common is sickle cell anemia?
 1 out of every 400-500 African Americans has sickle cell anemia
 In America, 2 million people are carriers of sickle cell allele
 Most common in west and central Africa
What are the symptoms of sickle cell anemia?
 Fatigue, breathlessness, and rapid heart rate
 Delayed growth and delayed puberty
 Increased susceptibility to infections
 Ulcers on the lower legs
 Jaundice
 Weakness, joint pain, attacks of abdominal pain, chest pain, excessive penis
pain
 Fever
 Vomiting
 Excessive thirst
 Decreased fertility
What treatment is available?
 Try to relieve pain
 Try to prevent infections
 Try to prevent eye damage and strokes
 Try to control complications as they occur

connection with malaria similar to CF’s connection with cholera
4. Tay-Sachs Disorder
What is Tay-Sachs? What is the cause of Tay-Sachs?
 fatal, genetic lipid storage disorder
 fatty substance builds up to dangerous levels, particularly in brain cells
 due to a faulty enzyme which is suppose to metabolize these fats
 this enzyme is found inside lysosomes of cells
How common is TSD?
 about 1 in every 27 Jews in U.S. is a carrier (particularly Ashkenazi Jews from
eastern Europe)
 French Canadians and Louisiana’s Cajun populations show similar frequencies
 about 1 in 50 Irish Americans are carriers
 in general population, incidence of carriers is about 1 in 300
What are the symptoms of TSD?
 infants appear normal for first few months of life
 an exaggerated startle reflex to noise often witnessed early on (while hearing still
intact)
 early diagnosis can be made by observing a “cherry-red” spot surrounded by a
white halo on the retina in the eye
 as nerve cells become distended with fats, there is a deterioration of both mental
and physical abilities
 eventually, child becomes blind, deaf, and unable to swallow
 seizures are also seen
 muscles atrophy and paralysis sets in
 all TSD babies die by 3-5 years of age
What treatment is available?
 very little to offer
 anticonvulsants, feeding tubes, and methods of keeping airway open utilized
5. Albinism
What is albinism? What is the cause of albinism?
 Characterized by the complete or partial absence of pigment in the skin, hair, and
eyes
 Enzyme responsible for the production of melanin absent or faulty
 Known to affect all vertebrates (fish, amphibians, reptiles, birds, mammals)
How common is albinism?
 Affects people of all backgrounds
 Frequency across the human population is about 1 in 20,000
 Groups which have demonstrated a high frequency of albinism include Native
Americans in both Panama (Kuna) and New Mexico (Zuni), Japanese, and
Africans living on Ukerewe Island in Lake Victoria within Tanzania
What are the symptoms of albinism?
 Most individuals appear white or very pale
 Skin more likely to burn as a result of exposure to sun’s uv radiation
 Lack of pigmentation in the eyes also leads to vision problems
What treatment is available?
 Eyes might need visual rehabilitation including surgery
 Special glasses and light sources often utilized