Genetic Disorders

Front 1

Describe changes in chromosome number or structure.

Back 1

Normal cells are diploid, containing 46 chromosomes, 22 pairs of autosomes and 1 pair of sex chromosomes, XX in females or XY in males.

Front 2

List types of changes in chromosome number or structure.

Back 2

1) Aneuploidy
2) Polyploidy
3) Deletion
4) Inversion
5) Translocation

Front 3

Describe aneuploidy.

Back 3

1) Chromosome number that is not a multiple of 23, the normal haploid number.
2) Caused most often by an addition or loss of one or two chromosomes; this change may result from nondisjunction or anaphase lag.

Front 4

Describe nondisjunction.

Back 4

1) Failure of chromosomes to separate during meiosis or mitosis. Meiotic nondisjunction is the most common cause of aneuploidy.
2) Responsible for disorders such as trisomy 21, the most common form of Down syndrome.

Front 5

Describe anaphase lag.

Back 5

1) Results in the loss of a chromosome during meiotic or mitotic division.
2) Early embryonic life, can result in mosaicism, in which an individual develops two lines of cells, one with a normal chromosome complement and another with monosomy, a single residual chromosome, for the affected chromosome pair.

Front 6

What is polyploidy?

Back 6

1) Is a chromosome number that is a multiple greater than two of the haploid number. Triploidy is three times the haploid number; tetraloidy is four times.
2) Rarely compatible with life and usually results in spontaneous abortion.

Front 7

Describe deletion.

Back 7

1) Most often absence of a portion of a chromosome, although it can be loss of an entire chromosome.
2) Denoted by a minus sign following the number of the chromosome and sign for the chromosomal arm infolved, p for the short arm and q for the large arm.

Front 8

Give an example of deletion.

Back 8

Cri du chat syndrome; characterized by partial loss of the short arm of chromosome 5, is designated as 46, XY, 5p- in males and 46, XX, 5p- in females.

Front 9

What is inversion?

Back 9

Reunion of a chromosome broken at two points, in which the internal fragment is reinserted in an inverted position.

Front 10

What is translocation?

Back 10

1) Exchange of chromosomal segments between nonhomologous chromosomes.
2) Denoted by a t followed by the involved chromosomes in numeric order; for example the translocation for of Down syndrome is designated as t(14q;21q)

Front 11

What is a reciprocal or balanced translocation?

Back 11

A break in two chromosomes leading to an exchange of chromosomal material. Because no genetic material is lost, balanced translocation is often clinically silent.

Front 12

What is a robertsonian translocation?

Back 12

A variant in which the long arms of two acrocentric chromosomes, chromosomes in which the short arm is VERY short, are joined with a common centromere, and the short arms are lost.

Front 13

What is Isochromosome formation?

Back 13

Is the result of transverse rather than longitudinal division of a chromosome, forming two new chromosomes, each consisting of either two long arms or two short arms. One of the two isochromosomes, usually the short-arm isochromosome, often is lost.

Front 14

Describe the Barr bodies.

Back 14

1) Also known as sex chromatin, are clumps of chromatin in the interphase nuclei of all somatic cells in females.
2) According to the lyon hypothesis, each Barr body represents one inactivated X chromosome. Thus, normal female cells have one Barr body; normal male cells have no Barr bodies; and XXXY cells have two Barr bodies. The number of Barr bodies is always one less than the number of X chromosomes.

Front 15

Describe X inactivation.

Back 15

1) The process by which all X chromosomes except one are randomly inactivated at an erly stage of embryonic development.
2) Results in all normal females being mosaics, with two distinct cell lines, one with an active maternal X, another with an active paternal X.
3) Can be demonstrated if the female is heterozygous for an X-linked gene; if individuals demonstrate inheritable disfferences that distinguish the protein products of one X chromosome from the other, members of the two cell lines can be identified.
4) X-inactive-specific transcript (XIST) is a large untranslated RNA molecule that is associated with "coating" and inactivation of one of the two X chromosomes. All except a single remaining X chromosome are inactivated.
5) The phenotypic differences between XO, XX, and multiple X genotypes are thought to be caused by residual genes on the X chromosome that escape inactivation.

Front 16

What are the two causes of Down Syndrome?

Back 16

Trisomy 21
Translocation

Front 17

Describe Trisomy 21.

Back 17

1) Accounts for 95% of cases, and incidence increases with maternal age.
2) Produced usually by a maternal meiotic nondisjunction. When the cause is paternal nondisjunction, there is no relation to paternal age.

Front 18

Describe Translocation in down syndrome.

Back 18

1) Leads to a familial form of DS, with significant risk of the syndrome in subsequent children.
2) Accounts for 3-5% of cases and has no relation to maternal age.
3) Caused by parental meiotic translocation between chromosome 21 and another chromosome. The fertilized ovum will have three chromosomes bearing the chromosome 21 material, the functional equivalent of trisomy 21.

Front 19

Describe the characteristics of down syndrome.

Back 19

1) Marked by severe mental retardation.
2) Large forehead, broad nasal bridge, wide-spaced eyes, epicanthal folds, large protruding tonge, and small low-set ears.
3) Brushfield spots, small white spots on the periphery of the iris.
4) Short, broad hands with curvature of the fifth finger; simian crease, a single palmar crease; and an unusually wide space between the first and second toes.

Front 20

What are the complications of down syndrome?

Back 20

1) Congenital heart disease, especially defects of the endocardial cushion, including atrioventricular valve malformations and atrial and ventricular septal defects.
2) Acute leukemia (20-fold increase), most often lymphoblastic.
3) Increased susceptibility to infection.
4) In patients surviving into middle age, morphologic changes in the brain similar to those of Alzheimer disease.

Front 21

What is the maternal screening for down syndrome?

Back 21

1) alpha-fetoprotein - LOW in down syndrome.
2) Human corionic gonadotropin (hCG) - HIGH in down syndrome.
3) Unconjugated estriol - low in Down syndrome.

Front 22

Describe Cri du chat syndrome.

Back 22

1) Caused by the deletion of the short arm of chromosome 5.
2) Characterized by severe mental retardation, microcephaly, adn an unusual catlike cry.
3) Further manifested by low birth weight, round face, hypertelorism (wide-set eyes), low-set ears, and epicanthal folds.

Front 23

Describe DiGeorge/velocardiofacial syndrome.

Back 23

1) Leads to a spectrum of clinical abnormalities formerly thought to be at least two seperate and distinct disorders.
2) Characterized by a set of finding summed up in the acronym CATCH 22, which denotes Cardiac abnormalities, Abnormal facies, T cell deficit because of thymic hypoplasia, Cleft palate, and Hypocalcemia because of hypoparathyroidism, all due to a microdeletion in chromosome 22.

Front 24

Describe edwards syndrome.

Back 24

1) Most frequently results form nondisjunction resulting in trisomy 18.
2) Marked by mental retardatin, prominent occiput, micrognathia, low-set ears, rocker-bottom feet, flexion deformities of the fingers (index overlapping third and fourth), and congenital heart disease.

Front 25

Describe Patau syndrome.

Back 25

Manifested by mental retardation, microcephaly, mocrophthalmia, brain abnormalities, cleft lip and palate, polydactyly, rocker-bottom feet, and congenital heart disease.

Front 26

Describe Kleinfelter syndrome.

Back 26

1) Disorder that occurs when there are at least two X chormosomes and one or more Y chromosomes. Most striking clinical changes are male hypogonadism and its secondary effects.
2) Always is manifest by a male phenotype with testes.
3) Most often characterized by karyotype 47, XXY. In this form, a single Barr body is noted in buccal smear preparations.
4) Most often caused by maternal meiotic nondisjunction, and incidence rises with maternal age.
5) Manifest by atrophic testes; tall stature, because fusionof the epiphyses is delayed; and a eunuchoid appearance with gynecomastia
6) marked by decreased testosterone production and increased pituitary gonadotropins form loss of feedback inhibition.
7) Frequent cause of male infertility.
8) Usually not associated with mental retardation. If presents, mental retardatin is usually mild, and the extent of retardation increases with increased number of X chromosomes.
9) Usually undiagnosed before puberty.

Front 27

Describe the XYY syndrome.

Back 27

1) occurs with increased frequency among criminals deonstrating violent behavior; the significance of this association is unknown, because only about 2% of XYY individuals display such behavioral abnormalities.
2) Manifest by tallness, severe acne, and only rarely by mild mental retardation.

Front 28

Describe Turner syndrome.

Back 28

1) Disorder that occurs when there is complete or partial monosomy of the X chromosome. The most striking clinical changes are female hypogonadism and its seondary effects.
2) Most common cause of primary menorrhea.
3) Most often characterized by an XO karyotype (45, X), in which no Barr bodies are seen on buccal smear.
4) Usually NOT complicated by mental retardation.

Front 29

What is turner syndrom characterized by?

Back 29

1) Replacement of the ovaries by fibrous streaks.
2) Decreased estrogen production and increased pituitary gonadotropins from loss of feedback inhibition.
3) Infantile genitalia and poor breast development
4) Short stature, webbed neck, shield-like chest with widely spaced nipples, and wide carrying angle of the arms
5) Lymphedema of the extremities and neck
6) Coarctation of the aorta and other congenital malformations.

Front 30

Describe XXX syndrome and other multi-X chromosome anomalies.

Back 30

1) Usually unaccompanied by any clinical abnormalities.
2) May be marked by menstrual irregularities or mild mental retardation. The degree of mental retardation appears to increase with the number of additional X chromosomes.

Front 31

Describe the general considerations of abnormalities due to increased numbers of trinucleotide repeats.

Back 31

1) The number of repeats often increases from generation to generation and is associated with earlier onset and more severe manifestations in successive generations. This is referred to anticipation.
2) Prominent examples of trinucleotide repeat disorders include fragile X syndrome, Huntington deasease, and myotonic dystrophy.

Front 32

What is fragile X syndrome?

Back 32

1) An important cause of hereditary mental retardation second in frequency only to Down syndrome.
2) Caused by a cytogenetically demonstrable defect on teh long arm of the X chromosome that leads to chromosome breakage in vitro.
3) Considered to be an X-linked disorder; however, the pattern of inheritance has a number of unusual features.

Front 33

Describe what happens in asymptomatic carriers of fragile X.

Back 33

1) Both males and females can be asymptomatic carriers.
2) Have an increased number of CGG tnadem repeats in the 5' untranslated region of the familial mental retardation (FMR-1) gene.
3) This increased number of repeats is referred to as a premutation.
4) In carrier females (but not males), premutations can expand in the germline to even greater increases in the number of tandem repeats. These increased numbers are referred to as full mutations.

Front 34

Describe what happens in transmitting carrier males of fragile X.

Back 34

Can transmit premutations through their daughters, who remain clinically unaffected but who can become carriers of X chromosomes wiht full mutations due to gerline expansion of the repeats.

Front 35

Describe what happens in transmitting carrier females of fragile X.

Back 35

1) Sons with full mutatins exhibit mental retardation and often bilateral macro-orchidism. The genetic defect can be further transmitted to all of their daughters.
2) Daughters with full mutations may or may not (~50%) exhibit mental retardatin. This unexplained phenomenon is possibly due to selective X inactivation, whereby affected females have a greater number of somatic cells with full mutations than do unaffected females.

Front 36

What is genomic imprinting?

Back 36

1) Hereditary disorders in which differing phenotypes occur depending on whether an abnormal gene is of maternal or paternal origin.
2) Thought that epigenetic changes occurring during gametogenesis mark at least some genes as of either maternal or paternal origin and can modify the later expresion of these genes when they are passed to teh next generation.
3) such marking is referred to as genomic impinting. the most likely explanation for this phenomenon is differing levels of DNA methylation in the female and male gonads, making certain genes nonactive, i.e., not able to be transcribed.

Front 37

What is Prader-Willi syndrome?

Back 37

1) Paternal transmission
2) Hypogonadism
3) Hypotonia
4) Mental retardation
5) Behavior problems
6) Uncontrolled appetite leading to obesity and diabetes.

Front 38

What is Angelmen syndrome?

Back 38

1) Maternal transmission
2) Sometimes referred to as happy puppet.
3) Characterized by mental retardation, but is additionally characterized by ataxia, seizures, and inappropriate laughter.

Front 39

What is autosomal dominant inheritance?

Back 39

1) One heterozygous parent carries a gene associated with phenotypic expression of a disorder adn the other parent is normal, by far the most likely case in nonconsanguineous matings.
2) One half of the children are expected to inherit the gene and are themselves heterozygotes who phenotypically manifest the gene.
3) Distribution of the phenotype is the same in both sexes.

Front 40

What is autosomal recessive inheritance?

Back 40

1) Both parents are heterozygotes who do not phenotypically manifest the disorder.
2) One in four of their children will be homozygous for teh trait and, in the case of disease states, will phenotypically manifest the disorder. Similarly, one in four of the children will not inherit the trait. Two of the children will be heterozygotes.
3) Distribution of the disordered phenotype is the same in both sexes.

Front 41

What is X-linked recessive inheritance?

Back 41

1) In the most frequent disease setting, the female parent is a heterozygous carrier, adn the male parent is genotypically and phenotypically unaffected.
2) The affected X chromosome will be inherited by one in two children' male children who inherit the affected X chromosome phenotypically manifest the disorder; heterozygous female children are carriers.
3) In a variant setting, the male parent carries the affected gene on the X chromosome and the female parent is unaffected.
4) All female children inherit the paternal X chromosome and become carriers; all male children are genotypically and phenotypically unaffected.

Front 42

What is X-linked dominant inheritance?

Back 42

A rare variant of X-linked inheritance. Heterozygous females as well as hemizygous males phenotypically manifest the disorder.

Front 43

What is mitochondrial inheritance?

Back 43

Mediated by maternally transmitted mitochondrial genes, which are inherited exclusively by maternal transmission.

Front 44

List eight Autosomal Dominant Disorders.

Back 44

1) Adult polycystic kidney disease
2) Familial hypercholesterolemia
3) Hereditary hemorrhagic telangiectasia
4) Hereditary spherocytosis
5) Marfan synrome
6) Neurofibromatosis
7) Tuberous sclerosis
8) von Hippel-Lindau disease

Front 45

What is adult polycystic kidney disease?

Back 45

1) Most frequently occurring hereditary renal disorder.
2) Characterized by numerous bilateral cysts that replace and ultimately destroy the renal PARENCHYMA.
3) Becomes clinically manifest between 30-50. Death usually occurs at about 50.

Front 46

What is familial hypercholesterolemia?

Back 46

1) Genetic defect characterized by anomalies of receptors for low-density lipoprotein.
2) Results in decreased transport of LDL cholesterol into cells, which causes hypercholesterolemia adn a striking increase in incidence and in earlier onset of atherosclerosis and its complications.
3) Further manifest by Xanthomas, raised yellow lesions filled with lipid-laden macrophages, in the skin and tendons.

Front 47

What is hereditary hemorrhagic telangiectasis?

Back 47

1) Rare disorder seen with increased frequency in certain populations, such as in Mormon families of Utah.
2) Characterized by localized telangiectases of the skin and mucous membranes and by recurrent hemorrhage from these lesions.

Front 48

What is hereditary spherocytosis?

Back 48

1) Caused by a variety of inherited defects of erythrocyte membrane-associated skeletal proteins.
2) Characterized by spheroidal erythrocytes that are sequestered and destroyed in the spleen, producing hemolytic anemia.

Front 49

What is Marfan syndrome?

Back 49

1) A defect of connective tissue characterized by faulty scaffolding.
2) apparently caused by a deficiency of fibrillin, a glycoprotein constituent of microfibrils.
3) Characterized by defects in skeletal, visual, and cardiovascular structures.
4) Patients are tall and thin with abnormally long legs adn arms, spider-like fingers, adn hyperextensible joints.
5) Dislocation of the ocular lens (ectopia lentis) is frequent.
6) Cystic medial necrosis can lead to aortic dilatin with resultant aneurysm of the proximal aorta, aortic valvular insufficieny, and dissecting aneurysm of the aorta. Loss of CT support may lead to mitral valve prolapse.

Front 50

What is neurofibromatosis?

Back 50

1) Distinguished by multiple neurofibromas in skin and other locations, schwannomas fo the VIIIth nerve, cafe au lait spots, and pigmented iris hamartomas (Lisch nodules). Benign neurofibromas can bcome malignant.
2) Marked by skeletal disorders, such as scoliosis and bone cysts, and increased incidence of other tumors, epecially pheochromocytoma and malignancies such as Wilms tumor, rhabdomyosarcoma, and leukemia.
3) Characterized by mutations in the NF1 gene, a tumor suppressor gene that normally codes for a GTPase-activating protein (GAP) that facilitates the conversion of active ras-GTP to inactive ras-GDP.

Front 51

What is tuberous sclerosis?

Back 51

1) Characterized by teh presence of glial nodules and distorted neurons in teh cerebral cortex.
2) Marked by seizures, mental retardation, and adenoma sebaceum (a facial skin lesion consisting of malformed blood vessels and connective tissue)
3) Associated with rhabdomyomas of the heart and with renal angiomyolipomas, lesions consisting of malformed blood vessels, smooth muscle, and fat cells.

Front 52

What is von Hippel-Lindau disease?

Back 52

1) Characerized by hemangioblastoma or cavernous hemangioma of the cerebellum, brain, or retina; adenomas; and cysts of the liver, kidney, pancreas, and other organs.
2) Associated with remarkably increased incidence of renal cell carcinoma. The gene for von Hippel-Lindau disease has been localized to the short arm of chromosome 3, deletion of which has been noted in many cases of sporadic renal cell carcinoma.

Front 53

What type of diseases are associated with autosomal recessive disorders?

Back 53

Autosomal recessive disorders
1) Lysosomal storage diseases
2) Glycogen storage diseases
3) Disorders of carbohydrate metabolism-galactosemia
4) Disorders of amino acid metabolism
5) Cystic fibrosis

Front 54

List four lysosomal storage diseases.

Back 54

1) Tay-Sachs disease
2) Gaucher disease
3) Niemann-Pick disease
4) Hurler syndrome

Front 55

What is a lysosomal storage disease?

Back 55

Group of disorders characterized by deficiency of a specific SINGLE lysosomal enzyme, resulting in an accumulation of abnormal metabolic products.

Front 56

What is Tay-Sachs disease?

Back 56

1) Most common form of gangliosidosis and occurs primarily in those of Ashkenazic Jewish descent.
2) Caused by a deficiency of hexosaminidase A, with consequent accumulation of GM2 ganglioside, especially in neurons.
3) Characterized by cnetral nervous system (CNS) degeneration, severe mental and motor deterioration, blindness, a characteristic cherry-red spot in the macula, and death before 4 years of age.

Front 57

What is Gaucher disease?

Back 57

1) Disorder of lipid metabilism caused by a deficiency of glucocerebrosidase, which results in an accumulation of glucocerebroside in cells of the mononuclear phagocyte system.
2) Can be identified by the presence of Gaucher cells, enlarged histiocytes with a distinctive "wrinkled tissue paper" cytoplasmic appearance.

Front 58

What is type I Gaucher disease?

Back 58

Accounts for about 80% of cases, is characterized by hepatosplenomegaly, erosion of the femoral head and of the long bones, and mild anemia. Gaucher cells are seen in the liver, spleen, lymph nodes, and bone marrow. A normal life span is possible.

Front 59

What is type II Gaucher disease?

Back 59

1) Infantile Gaucher disease
2) Marked by severe CNS involvement and results in death before 1 year of age.
3) There is no detectable glucocerebrosidase in the tissues

Front 60

What is type III Gaucher disease?

Back 60

1) Juvenile Gaucher disease
2) Invloves both the brain and the viscera but is less severe than type II.
3) Onset is usually in early childhood.

Front 61

What is Niemann-Pick disease?

Back 61

1) Most often caused by a deficiency of sphingomyelinase, with consequent sphingomyelin accumulation in phagocytes.
2) Characterized by "foamy histiocytes", containing sphingomyelin which proliferate in the iver, spleen, lymph nodes, and skin.
3) Marked by hepatosplenomegaly, anemia, fever, and, in some variants, by neurologic deterioration.
4) About half of the patients have a cherry-red spot in the macula similar to that of Tay-Sachs disease.
5) Death occurs by 3 years of age.

Front 62

What is Hurler syndrome?

Back 62

1) mucopolysaccharidosis that is caused by deficiency of alpha-L-iduronidase, with consequent accumulations of the mucopolysaccharides heparan sulfate adn dermatan sulfate in teh heart, brain, liver, and other organs.
2) Marked by progressive deterioration, hepatosplenomegaly, dwarfism, gargoyle-like facies, stubby fingers, corneal clouding, progressive mental retardation, and death by 10 years of age.
3) Clinically similar to, but should not be confused with Hunter syndrome, which is X-linked.

Front 63

What are glycogen storage diseases?

Back 63

Group of disorders caused by defects in the synthesis or degradation of glycogen.

Front 64

List four glycogen storage diseases.

Back 64

1) von Gierke disease
2) Pompe disease
3) Cori disease
4) McArdle syndrome

Front 65

What is von Gierke disease?

Back 65

1) Glycogen storage disease type I, or hepatorenal glycogenosis
2) Caused by a deficiency of glucose-6-phosphatase, with consequent accumulation of glycogen, primarily in the liver and kidney.
3) Characterized by hepatomegaly and sometimes by intractable hypoglycemia.

Front 66

What is Pompe disease?

Back 66

1) Glycogen storage disease type II, but can also be classified as a lysosomal storage disease.
2) Caused by a deficiency of alpha-1,4-glucosidase, with consequent accumulatin of glycogen, especially in the liver, heart, and skeletal muscle.
3) Characterized by cardiomegaly, muscle hypotonia, and splenomegaly
4) Death by cardiorespiratory failure before 3 years of age.
5) Can also be characterized by intractable hypoglycemia.

Front 67

What is Cori disease?

Back 67

1) Glycogen storage disease type III.
2) Caused by a deficiency of the debrancing enyme, amylo-1,6-glucosidase, leading to variable accumulation of glycogen in the liver, heart, or skeletal muscle.
3) Characterized by stunted growth, hepatomegaly, and hypoglycemia.

Front 68

What is McArdle syndrome?

Back 68

1) Glycogen storage disease type V
2) Caused by deficiency of muscle phosphorylase, with consequent glycogen accumulation in skeletal muscle.
3) Produces painful muscle cramps and muscle weakness following exercise.

Front 69

List two disorders of carbohydrate metabolism.

Back 69

1) Classic Galactosemia
2) Galactokinase-deficiency galactosemia.

Front 70

What is Classic Galactosemia?

Back 70

1) Caused by deficiency of galactose-1-phosphate uridyl transferase, with resultant accumulation of galactose-1-phosphate in many tissues.
2) Marked by failure to thrive, infantile cataracts, mental retardation, and progressive hepatic failure leading to cirrhosis adn death.
3) Most of thees changes can be prevented by early removal of galactose form the diet.

Front 71

What is Galactokinase-deficiency galactosemia?

Back 71

1) Much less frequent than classic form
2) Often marked only by infantile cararacts.

Front 72

List three disorders of amino acid metabolism.

Back 72

1) Phenylketonuria (PKU)
2) Alkaptonuria
3) Maple syrup urine disease

Front 73

What is Phenylketonuria (PKU)?

Back 73

1) In most cases is caused by mutation of the phenylalanine hydroxylase gene. Phelylalanine hydroxylase deficiency results in failure of vonversion of phenylalanine to tyrosine in the liver.
2) Results in high serum concentrations of phenylalanine, which are neurotoxic and cause progressive cerebral demyelination.Phenylpyruvic acid adn phenylacetic acid accumulate in the urine.

Front 74

What is PKU characterized by?

Back 74

1) Progressive mental deterioration, usually pronounced by one year.
2) Seizures
3) Hyeractivity
4) Decreased pigmentation of hair, eyes, and skin
5) Musty body odor from Phenylacetic acid in Urine and sweat.

Front 75

How is PKU treated?

Back 75

1) Phenylalanine-free diet.
2) Screening tests for serum phenylalanine or urinary catabolites are usually performed on teh third or forth day of life.
3) Earlier screening may result in false-negative results.

Front 76

What is alkaptonuria?

Back 76

1) Caused by incomplete metabolism of phenylalanine and tyrosine due to deficiency of homogentisic oxidase, leading to accumulation and urinary excretion of homogentisic acid.
2) Characterized by urine that turns dard adn finally black on standing; ochronosis, dark pigmentation of fibrous tissues and cartilage; and incapacitating ochronotic arthritis.
3) Cardiac valves may also be involved.

Front 77

What is maple syrup urine disease?

Back 77

1) Rare inborn error of metabolism that can be caused by any of a number of defects in the proteins that make up the branched-chain alpha-keto acid dehydrogenase complex.
2) Characterized by mental and physical retardation, feeding problems, and a maple syrup ordor to the urine.
3) Further characterized by high urinary levels of the keto acits of leucine, isoleucine, and valine.
4) If untreated, results in mental and physical disabilities adn often leads to neonatal death.
5) Can be detected by newborn screening programs and can be minimized in severity when treated with protein-modified diets

Front 78

What is cystic fibrosis?

Back 78

1) One of the most common lethal genetic diseases among whites.
2) mutations in the CFTR gene, which has been localized to the midsection of the long arm of chromosome 7; codes for a membrane protein that facilitats the movement of chloride and other ions across membranes.
3) Characterized by malfunction of exocrine glands, resulting in increased viscosity of mucus and increased chloride concentration in sweat and tears. Secretion by sweat glands of chloride and sodium is normal, but their reabsorption by sweat ducts is impaired.

Front 79

How is cystic fibrosis manifested clinically?

Back 79

1) Chronic pulmonary disease; retention of viscid mucus, which leads to secondary infection; recurrent bouts of pneumonia, severe chronic bronchitis, bronchiectasis, and lung abscess are common. Infection with Pseudomonas aeruginosa is a common cause of death in cystic fibrosis.
2) Pancreatic insufficiency; deficiency of pancreatic enzymes that leads to malabsorptin and steatorrhea.
3) Meconium ileus; small-bowel obstruction in the newborn caused by thick, viscous meconium.

Front 80

List six X-linked recessive disorders.

Back 80

1) Hunter syndrome.
2) Fabry disease
3) G6PD deficiency
4) Classic hemophilia (A)
5) Lesch-Nyhan syndrome
6) Duchenne muscular dystrophy

Front 81

What is Hunter syndrome?

Back 81

1) Lysosomal storage disease, a form of mucopolysaccharidosis clinically similar to, but less severe than, Hurler syndrome.
2) Caused by deficiency of L-iduronosulfate sulfatase, resulting in accumulation of heparan sulfate and dermatan sulfate.
3) Characterized by hepatosplenomegaly, micrognathia, retinal degeneration, joint stiffness, mild mental retardation, and cardiac lesions.

Front 82

What is Fabry disease?

Back 82

1) lysosomal storage disease caused by deficiency of alpha-galactosidase A, with resultant accumulatin of ceremide trihexoside in body tissues.
2) Marked by characteristic skin lesions over the lower trunk, febrile episodes, severe burning pain in the extremities, adn cardiovascular adn cerebrovascular involvement.
3) Results in death in early adult life from renal failure.

Front 83

What is classic hemophilia (A)?

Back 83

1) Relatively common X-linked disorder caused by mutations affecting teh factor VIII gene, which has been localized to the tip of the long arm of the X chromosome.
2) Manifest as deficiency of coagulation of factor VIII
3) Marked by hemorrhage from minor wounds and trauma, bleeding from oral mucosa, hematuria, and hemarthroses. Recurrent hemarthroses can lead to progressive crippling deformities.

Front 84

What is Lesch-Nyhan syndrome?

Back 84

1) Caused by deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT), with resultant impaired puring metabolism and excess production of uric acid.
2) Characterized by gout, mental retardation, choreoathetosis, spasticity, self-mutilation, and aggressive behavior.

Front 85

What are polygenic disorders?

Back 85

1) More common than monogenic disorders
2) Result from abnormalities of complex processes that are regulated by the protein products of two or more genes. Environmental factors also play an important role in the modulation of the genetic defects
3) Include such common entities as ischemic heart disease, diabetes mellitus, hypertension, gout, schizophrenia, bipolar disorder, and neural tube defects..

Front 86

What is genetic sex definition?

Back 86

Determined by the presence or absence of a Y chromosome. At least one Y chromosome is necessary for male gender to be manifest.

Front 87

What is gonadal sex definition?

Back 87

Determined by the presence of ovaries or testes. The gene responsible for development of the testes (H-Y gene) is localized to the Y chromosome.

Front 88

What is genital sex definition?

Back 88

Based on the appearance of the external genitalia.

Front 89

What is a true hermaphrodite?

Back 89

1) Rare
2) Both ovarian and testicular tissue, with ambiguous external genitalia adn both X adn Y chromosomes.
3) May sometimes result from the fusion of two sperm with a binucleated ovum.

Front 90

What is a pseudohermaphrodite?

Back 90

Has gonads of only one sex, but the appearance of the external genitalia does not correspond to teh gonads present.

Front 91

What is a male pseudohermaphrodite?

Back 91

1) May be caused by tissue resistance to androgens (testicular feminization), defects in testosterone synthesis, or hormones administered to the mother during pregnancy.
2) Has also been linked to chromosomal anomalies, such as 46, XY/45, X mosaicism.

Front 92

What is female pseudohermaphrodite?

Back 92

Most often caused by increased androgenic hormones form congenital adrenal hyperplasia, an androgen-secreting adrenal or ovarian tumor in teh mother, or hormones administered to teh mother during pregnancy.