Ch 5&10 Genetic And Congenital Disorders Flashcards
0
Q
How much of congenital defects are caused by chromosomal abnormalities?
A
2%
0
Q
What can the soft skull in OI type II cause during delivery?
A
Intracranial hemorrhage and stillbirth
1
Q
What are the four main stages in prenatal development?
A
- Preimplantation embryonic stage
- Germ layer formation
- Early organogenesis
- Definite organogenesis
2
Q
Three types of exogenous teratogens?
A
- Physical
- Chemical
- Microbial
2
Q
What is the most severe NON-LETHAL type of OI?
A
Type III
3
Q
Examples of physical teratogens?
A
X rays, corpuscular radiation
3
Q
Signs/symptoms of OI type III?
A
Short stature, spinal curvature, multiple recurrent fractures, macrocephaly with triangular faces. Scleral hue varies.
4
Q
Examples of chemical teratogens?
A
Industrial chemicals, drugs, alcohol
4
Q
What is the severity of OI type IV?
A
Intermediate
5
Q
Examples of microbial teratogens?
A
Viruses, bacteria, protozoal parasites
5
Q
Signs/symptoms of OI type IV?
A
Bones fracture easily in childhood, moderate-short stature. Sclera typically NORMAL in color
6
Q
What is thalidomide?
A
Exogenous teratogen - prevented morning sickness
6
Q
Why is accurate diagnosis of type IV OI important?
A
Patients may benefit from treatment
7
Q
What effect does thalidomide have on babies?
A
Phocomelia (flipper-like arms or legs)
7
Q
What are blue sclerae characteristically associated with?
A
heritable disorders of connective tissue
8
Q
Where was thalidomide used in the fifties/sixties?
A
UK, Canada, Germany, Japan
NOT IN US
8
Q
Why does blue discoloration occur in sclera?
A
Thinning of sclera allows underlying choroid to become visible.
9
Q
How common are fetal alcohol spectrum disorders (FASDs)?
A
0.2 to 1.5 per 1000 live births in US
9
Q
What is Familial Hypercholesterolemia AKA?
A
Hyperlipidemia type IIA
10
Q
Characteristics of FASDs?
A
see list slide 11
10
Q
What is Familial Hypercholesterolemia?
A
Elevated LDLs owing to defective or absent LDL receptors
11
Q
What does T stand for in TORCH syndrome?
A
Toxoplasma
11
Q
What is the approx. cholesterol level in heterozygotes of familial hypercholesterolemia?
A
~300mg/dL
12
Q
What does O stand for in TORCH?
A
(Others)
Less common viruses Ex Epstein Barr, varicella virus, listeria monocytogenes, leptospira
12
What is the approx. cholesterol level in homozygotes of familial hypercholesterolemia?
~700+ mg/dL
13
What does R stand for in TORCH?
Rubella
13
What other signs and symptoms will homozygotes for familial hypercholesterolemia exhibit?
severe atherosclerotic disease early in life, tendon xanthomas (classicaly in Achilles tendon), MI may develop before age 20
14
What does C stand for in TORCH?
Cytomegalovirus (CMV)
14
Normal LDL receptor pathway?
LDL endocytosed into clathrin coated pit -> Coated vesicle -> Endosome -> lysosome -> Free Cholesterol -> Cell membrane, steroid hormones, bile acids
15
What does H stand for in TORCH?
Herpesvirus
15
How are VLDLs normally metabolized?
Lipolysis via lipoprotein lipase
16
What does (S) stand for in TORCH(eS)?
Syphilis
16
How are LDL receptor mutations classified?
Based on abnormal function of the mutant protein
17
What does rubella cause?
Small/structurally abnormal brain
| Heart defects
17
How is each class of LDL receptor mutation characterized at the DNA level?
HETEROGENOUS
18
What do toxoplasma and CMV cause?
Micro calcification of basal ganglia and dilation of lateral ventricles (hydrocephalus)
CNS defects
18
Treatment of familial hypercholesterolemia? (3)
Nicotinic acid, high dietary fiber, statin drugs
19
What does herpesvirus cause?
CNS defects
| Skin lesions
19
What are the effects of nicotinic acid?
Increases HDL, lowers TGs, lowers LDL (higher doses), lower Lp(a)
20
Symptoms of congenital rubella syndrome?
Microcephaly, heart disease, petechiae/purpura, eye anomalies
20
Frequent adverse effects of nicotinic acid?
Flushing, impaired glucose tolerance, increased uric acid.
21
Two types of chromosomal anomalies?
Structural and numerical
21
How do you minimize flushing with nicotinic acid?
Use aspirin and give with food
22
Types of structural chromosomal abnormalities?
Translocation, isochromosomes, deletions, inversions, ring chromosomes
22
What is the inheritance pattern for polycystic kidney disease?
autosomal dominant (adult form) or autosomal recessive (juvenile form)
23
Types of numerical chromosomal abnormalities?
Aneuploidy, hyperdiploidy, hypodiploidy, monosomy, trisomy
23
What is the incidence of autosomal dominant PKD?
1/1000
24
What is aneuploidy?
Loss or gain of chromosomes
24
What percentage of end-stage renal disease patients are due to PKD?
5-10%
25
What is hyperdiploidy?
Specific type of aneuploidy
| 46+1, 46+2
25
How often are clinical manifestations of ADPKD before adulthood?
RARE
26
What is hypodiploidy?
Specific type of aneuploidy
| 46-1, 46-2
26
Incidence of autosomal recessive PKD?
RARE - 1/10000
27
What is FISH?
Fluorescence in situ hybridization
27
What does recessive PKD often cause in childhood?
Renal failure
28
What is trisomy 21?
Down syndrome
28
What is PKD associated with?
polycystic liver disease, BERRY ANEURYSMS, mitral valve prolapse
29
Characteristics of Down syndrome?
Mental retardation, unique facial features, eye abnormalities, gaping mouth, large tongue, heart diseases, intestinal defects, hand abnormalities, toe abnormalities
29
What are 86-96% of ADPKD cases caused by?
mutations in PKD1 GENE on chromosome 16
30
What is the major risk factor for Down syndrome?
AGe of mother
30
What are most other cases of ADPKD caused by?
mutations in PKD2 GENE on chromosome 4
31
What is the incidence of Down syndrome?
1 in 700 births
31
What does polycystin 1 regulate?
Tubular epithelial cell adhesion and differentiation
32
What is the Incidence of Edwards syndrome?
1 in 8000 births
32
What does polycystin 2 regulate?
ion channel, mutations cause fluid secretion into cysts
33
What is the incidence of Patau syndrome?
1 in 15000 births
33
What are tubular cell proliferation and differentiation linked to?
Flow rate
34
What is Edwards syndrome ?
Trisomy 18
34
What may ciliary dysfunction lead to?
Cystic transformation
35
What is Patau syndrome?
Trisomy 13
35
What is the prognosis for PKD?
By age 75, 50-75% of patients require renal replacement therapy (dialysis or transplant)
36
What is the most common autosomal trisomy?
Down syndrome
36
What is the Tx for PKD?
Strict BP control, restricted protein intake.
37
What is the life expectancy of Down syndrome ?
45-50 years
37
Is PKD bilateral or unilateral?
ALWAYS BILATERAL
38
What is the life expectancy of Edwards syndrome?
<1 year
38
What is spherocytosis?
Congenital RBC membrane disorder
39
What is the life expectancy of Patau syndrome?
<1 year
39
Symptoms of spherocytosis?
variable degrees of anemia, jaundice, and splenomegaly
40
What is the most common cause of mental retardation?
Down syndrome
40
What does diagnosis of spherocytosis require?
demonstration of increased RBC osmotic fragility and a NEGATIVE direct antiglobulin test
41
What is the level of mental retardation with Edwards syndrome?
Severe
41
What do patients <45 yrs with symptomatic disease require?
splenectomy
42
What is the level of mental retardation with patau syndrome?
Severe
42
What causes RBC abnormalities in spherocytosis?
alterations in membrane proteins
43
Other disease risks with Down syndrome?
ALL, Alzheimer's >35
43
What happens to cell membrane surface area during spherocytosis?
Decreased disproportionately to intracellular content
44
Characteristics of head/face in Down syndrome?
Flat facial profile, prominent epicanthal folds
44
What does decreased surface area of cell in spherocytosis impair?
Impairs flexibility needed for cell to traverse spleen's microcirculation => intrasplenic hemolysis
45
Characteristics of head/face in Edwards syndrome?
Prominent occiput, micrognathia, low set ears
45
What is considered curative for spherocytosis in western medicine?
splenectomy
46
Characteristics of head/face in Patau syndrome?
Micropthalmia, microcephaly, cleft lip/palate
46
What does presence of spherocytes in peripheral blood smear suggest?
EITHER hereditary spherocytosis (HS) or autoimmune hemolytic anemia (AIHA)
47
Are congenital heart defects associated with Down syndrome?
Yes especially septum primum type ASD
| Due to endocardial cushion defects
47
How do you distinguish between HS and AIHA?
Coombs' test. POSITIVE in AIHA, NEGATIVE in HS
48
Are congenital heart defects associated with Edwards syndrome?
Yes
48
What is Huntington disease?
Autosomal dominant disorder characterized by chorea and progressive cognitive deterioration
49
Are congenital heart defects associated with Patau syndrome?
Yes
49
When do symptoms of Huntington disease usually begin?
Middle age
50
Hand characteristics in Down syndrome?
Simian crease
50
How is Huntington disease diagnosed?
Genetic testing
51
Hand characteristics in Edwards syndrome?
Clenched hands
51
What is the treatment for Huntington disease?
Supportive
52
Hand characteristics in Patau syndrome?
Polydactyly
52
Who should get tested for Huntingtons?
First-degree relatives
53
Feet characteristics of down syndrome?
Gap between first two toes
53
Which sex is more affected by Huntingtons?
BOTH affected EQUALLY
54
Feet characteristics of edwards syndrome?
Rocker bottom feet
54
What happens to caudate nucleus in Huntingtons?
atrophies
55
Feet characteristics of patau syndrome?
Rocker bottom feet
55
What happens to medium spiny neurons in corpus striatum in Huntingtons?
Degenerate
56
Two abnormalities of sex chromosomes?
Turner syndrome
| Klinefelter syndrome
56
What happens to levels of GABA and substance P in Huntingtons?
Decrease
57
What is the main pathogenesis of turners and klinefelters syndrome?
NONDISJUNCTION
57
What does Huntington's disease result from?
Gene mutation on chromosome 4, causing abnormal repetition of DNA sequence CAG (which codes for glutamine)
58
What is incidence of Turner syndrome?
1 in 3000 female births
58
What is the resulting gene product of the mutation in Huntingtons?
Large protein called huntingtin
59
Characteristics of Turner syndrome?
*list slide 30*
59
How does huntingtin lead to disease?
unknown mechanisms
60
What is the most common cause of primary amenorrhea?
Turner syndrome
60
What happens with increased CAG repetitions?
More repetitions = earlier disease begins and more severe effects
61
What gender do turners syndrome present as?
Female
61
How can the number of repeats of CAG increase?
With successive generations
62
Characteristics of klinefelters syndrome?
*list slide 31*
62
What can increasing repeats of CAG lead to over time?
more severe phenotype within a family tree
63
What gender do klinefelters syndrome present as?
Male
63
Signs/symptoms of Huntingtons?
Dementia/psychiatric disturbances, abnormal movements (myoclonic jerks, irregular movements of extremeties, lilting gate, grimacing, ataxia, tongue protrusion)
64
Four types of single gene defects?
Alleles - genes expressed in duplicate
Homozygotes
Heterozygotes
Sex chromosome linked genes
64
How does Huntingtons progress?
Makes walking impossible, swallowing difficult, severe dementia. Death usually occurs 13 to 15 yrs after symptoms begin
65
5 types of Mendelian inheritance?
1. Autosomal dominant
2. Autosomal recessive
3. Sex linked recessive
4. Sex linked dominant
5. Mitochondrial inheritance
65
What is the usual cause of death of Huntingtons patients?
Pneumonia or coronary artery disease
66
When are autosomal dominant trait expressed?
In heterozygotes or homozygotes
66
What are the trinucleotide repeat expansion diseases?
Huntingtons dz, myotonic dystrophy, friedreich's ataxia, fragile x syndrome
67
Which generations are affected with autosomal dominant Inheritance?
EVERY generation
67
What is genetic anticipation?
in each successive generation the disease severity INCREASES and the age of onset DECREASES
68
What are the chances of an affected heterozygote transmitting an autosomal dominant gene to their offspring?
50%
68
When are autosomal recessive traits expressed?
In homozygotes
69
What are the chances of an affected homozygote transmitting an autosomal dominant gene to their offspring?
100%
69
What percentage of offspring from 2 carrier parents will be affected in autosomal recessive traits?
25%
70
Will unaffected offspring of symptomatic carrier of autosomal dominant gene transmit the trait?
NO
70
What are autosomal recessive disorders often due to?
enzyme deficiencies
71
What are the odds of transmission of an autosomal dominant gene from two heterozygotes to their offspring?
25% homozygote carrier
50% heterozygote
25% unaffected
71
When do autosomal recessive disorders usually present?
CHILDHOOD
72
What is the affected tissue in marfan's syndrome?
Connective tissue
72
How severe are autosomal recessive disorders?
Commonly MORE severe than dominant
73
What is the affected tissue in achondroplastic dwarfism?
Bones
73
Examples of autosomal recessive disorders?
Cystic fibrosis, amino acid disorders, anemias, hemochromatosis, alpha1-antitrypsin deficiency, glycogen storage disease, lysosomal storage diseases, infant PKD
74
What is the affected tissue in osteogenesis imperfecta?
Bones
74
What is cystic fibrosis?
Autosomal-recessive defect in CFTR gene on chromosome 7 (commonly deletion of Phe508).
75
What is the affected tissue in familial hypercholesterolemia?
Cardiovascular system
75
What is the most common LETHAL genetic disease of caucasians?
Cystic fibrosis
76
What is the affected tissue in adult polycystic kidney disease?
Kidney
76
What is the function of CFTR channel?
actively secretes Cl- in lungs and GI tract, actively reabsorbs Cl- from sweat
77
What is the affected tissue in Wilm's tumor ?
Kidney
77
What happens due to a defect in CFTR gene?
Cl- ion dysfunctional => secretions become more viscous
78
What is the affected tissue in spherocytosis?
Hematopoietic system
78
What causes infertility in males with cystic fibrosis?
Bilateral ABSENCE of vas deferens
79
What is the affected tissue in familial polyposis coli?
GI system
79
What vitamins are often deficient in cystic fibrosis patients?
fat soluble (ADEK)
80
What is the affected tissue in Huntingtons disease?
Nervous system
80
How do vitamin deficiencies present in infants with cystic fibrosis?
As failure to thrive
81
What is the affected tissue in neurofibromatosis?
Nervous system
81
Treatment for cystic fibrosis?
N-acetylcysteine to loosen mucous plugs (found in glutathione)
82
Characteristics of marfan's syndrome?
*list slide 37*
82
Pathogenesis of cystic fibrosis?
Defective Cl- channel -> secretion of abnormally thick mucus -> plugs lungs, pancreas, and liver -> recurrent pulmonary infections/chronic bronchitis, bronchiectasis, pancreatic insufficiency
83
Inheritance of marfan's syndrome?
Autosomal dominant
83
What does cystic fibrosis cause in infants?
Meconium ileus
84
Basic molecular defect in marfan's syndrome?
Mutations in gene encoding glycoprotein FIBRILLIN-1 (FBN1)
84
What is a diagnostic test for cystic fibrosis?
High concentration of Cl- ions in SWEAT TEST
85
What does fbn1 do?
Helps anchor cells to ECM
85
What is the common cause of cystic fibrosis?
Three-base deletion - usually Phe508
86
What are the principle structural defects involved in marfans syndrome?
Cardiovascular, musculoskeletal, and ocular systems
86
Is cystic fibrosis a frameshift mutation?
NO (deletion is a multiple of 3)
87
How is marfan's syndrome typically recognized?
Combination of long limbs, aortic root dilation, and dislocated lenses
87
What is sickle cell anemia?
Chronic hemolytic anemia occuring almost exclusively in African Americans
88
What is the most common and best known type of short limbed dwarfism?
Achondroplastic dwarfism
88
What causes sickle cell anemia?
homozygous inheritance of Hb S
89
Signs and symptoms of achondroplastic dwarfism?
Bulky forehead, saddle nose, exaggerated lumbar lordosis, bowlegs
89
What does sickle cell anemia cause?
sickle shaped RBCs - clog capillaries, causing organ ischemia
90
Defective gene product of achondroplastic dwarfism?
Fibroblast growth factor (FGF) receptor 3
90
What may develop frequently with sickle cell anemia?
Acute pain (crises)
91
Inheritance of achondroplastic dwarfism?
Autosomal dominant
91
What can develop acutely and be fatal in sickle cell anemia?
Infection, bone marrow aplasia, lung involvement
92
What is osteogenesis imperfecta?
Hereditary collagen disorder causing diffuse abnormal fragility of bone
92
Pathophysiology of sickle cell anemia?
In Hb S, VALINE is substituted for GLUTAMIC ACID in the 6TH AMINO ACID of the BETA CHAIN
93
Four main types of OI?
I, II, III, IV
93
Why does Hb S cause RBCs to deform in sickle shape?
Less soluble than HbA, forms semisolid gel at sites of low PO2
94
Which types of OI are autosomal dominant?
Type I and IV
94
How do deformed RBCs lead to infarction?
adhere to vascular endothelium and plug small arterioles/capillaries
95
Which types of OI are autosomal recessive?
Types II and III
95
What does venous plugging predispose to?
Thromboses
96
How often is hearing loss present in OI patients and in what types?
50-65%
| May occur in ALL FOUR TYPES
96
What does mechanical trauma of circulation produce in sickle cell anemia?
Hemolysis
97
What is the mildest form of OI?
Type 1
97
What deforms the bones in sickle cell anemia?
Chronic compensatory marrow hyperactivity
98
Signs and symptoms of type I OI?
Blue sclerae, musculoskeletal pain due to jt hypermobility
| Possible recurrent fractures in childhood
98
What is a point mutation?
single base pair change in DNA
99
What is the most severe and LETHAL type of OI?
Type II
99
What are lysosomal storage diseases?
category of many diseases each caused by a specific deficiency in one of many lysosomal enzymes
100
Signs/symptoms of type II OI?
Multiple congenital fractures, blue sclerae, soft skull (feels like "bag of bones")
100
Two categories of lysosomal storage diseases?
Sphingolipidoses and mucopolysaccharidoses
101
Two examples of sphingolipidoses?
Niemann-Pick disease, Tay-Sachs disease
102
Two examples of mucopolysaccharidoses?
Hurler's syndrome, Hunter's syndrome (not autosomal recessive - X linked disease)
103
What is the affected enzyme affected in Niemann-Pick disease?
Sphingomyelinase
104
What is the affected enzyme affected in Tay-Sachs disease?
Hexosaminidase A
105
What is the inheritance pattern for Niemann-Pick disease?
Autosomal recessive
106
What is the inheritance pattern for Tay-Sachs disease?
Autosomal recessive
107
What is the inheritance pattern for Hurler's syndrome?
Autosomal recessive
108
What is the inheritance pattern for Hunter's syndrome?
X-linked recessive
109
What does microscopic view of Tay Sachs disease show?
swollen and vacuolated neural system, myelin figures composed of concentric membranes
110
Why is the neural system swollen and vacuolated in Tay Sachs disease?
Due to increased # of lipid rich lysosomes
111
Does Tay Sachs disease involve a frameshift mutation?
YES - four base insertion
112
What is a common ethnic group affected by Tay Sachs?
Ashkenazi Jews
113
How do hepatocytes and Kupffer cells appear microscopically with Niemann-Pick disease?
Foamy vacuolated appearance due to deposition of lipids
114
What is inheritance pattern of phenylketonuria (PKU)?
Autosomal recessive
115
What ethnicities are most commonly affected by PKU?
White populations
116
Incidence of PKU?
1/10,000 births among whites
117
What normally converts excess dietary phenylalanine to TYROSINE?
Phenylalanine hydroxylase
118
What is the essential cofactor for phenylalanine hydroxylase?
tetrahydrobioperitin (BH4)
119
What happens if gene mutation results in deficiency/absence of phenylalanine hydroxylase, and what organ is most affected?
Dietary phenylalanine accumulates - BRAIN is main organ affected
120
What happens to excess phenylalanine?
Metabolized to phenylketones, which are excreted in urine
121
What is the normal cascade of phenylalanine?
Phenylalanine -> tyrosine -> dopa -> dopamine -> NE -> epinephrine
122
PKU is a clinical syndrome of what?
mental retardation
123
What causes mental retardation in PKU?
elevated serum phenylalanine
124
Other findings in PKU?
growth retardation, fair skin, eczema, musty body odor
125
Primary cause of PKU?
deficient phenylalanine hydroxylase activity
126
Another cause of PKU?
decreased tetrahydrobiopterin cofactor
127
How is PKU diagnosed?
By detecting high phenyalanine levels and normal or low tyrosine levels
128
Is PKU screened for at birth?
YES - heel prick
129
What are the phenylketones produced in PKU?
Phenylacetate, phenyllactate, and phenylpyruvate
130
Why is there a characteristic musty body odor with PKU?
disorder of AROMATIC amino acid
131
Tx for PKU?
lifelong dietary PHENYLALANINE restriction and increased TYROSINE in diet
132
Prognosis for PKU?
excellent with treatment
133
Glycogen storage disease (GSD) type 1 - enzyme deficiency?
glucose-6-phosphate
134
GSD type 2 - enzyme deficiency?
acid maltase
135
GSD type 3 - enzyme deficiency?
glycogen debrancher
136
GSD type 5 - enzyme deficiency?
MUSCLE glycogen phosphorylase
137
GSD type 6 - enzyme deficiency?
LIVER glycogen phosphorylase
138
GSD type 1 - eponym?
von Gierke's disease
139
GSD type 2 - eponym?
Pompe's disease
140
GSD type 3 - eponym?
Cori's disease or Forbe's disease
141
GSD type 5 - eponym?
McArdle disease
142
GSD type 6 - eponym?
Hers' disease
143
Findings in von Gierke's disease?
severe FASTING HYPOGLYCEMIA, increase glycogen in liver, increased blood lactate, HEPATOMEGALY
144
Findings in Pompe's disease?
CARDIOMEGALY and systemic findings leading to early death (heart, liver and muscle)
145
Findings in Cori's disease?
Milder form of type 1 with normal blood lactate levels. Gluconeogenesis is INTACT
146
Findings in McArdle disease?
Increased glycogen in MUSCLE, but cannot break it down => painful muscle cramps, myoglobinuria w/ strenuous exercise
147
What does Pompe disease look like microscopically?
Myocardial fibers full of glycogen seen as clear spaces
148
What is the chance of sons of heterozygous mothers will be affected with X-linked recessive disorders?
50% chance
149
Is there male-to-male transmission of X linked recessive disorders?
NO
150
In which sex are X linked recessive disorders more severe?
MALES
151
Will heterozygous females be affected with X linked recessive disorders?
Can be
152
When will females show phenotype of x linked recessive disorders?
Homozygous females
153
What are the X linked recessive disorders?
Bruton's agammaglobulinemia, Wiskott-Alrich syndrome, Immunodeficiency, FragileX, Lymphoproliferative disorders, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Dystrophies (Duchenne's MD, Becker's MD), Hemophilia A and B, Fabry's disease, Hunter's syndrome
154
Mnemonic to remember X linked recessive disorders?
Be Wise, FooL's GOLD Heeds False Hope
155
What is Fragile X syndrome?
X linked defect affecting the methylation and expression of FMR1 gene
156
What is the mutation in Fragile X syndrome?
CGG triple nucleotide repeat
157
What is the 2nd most common genetic mental retardation?
Fragile X syndrome
158
What is the most common mental retardation in MALES?
Fragile X syndrome
159
Clinical signs of Fragile X syndrome?
macro-orchidism, long face w/ large jaw, large everted ears, autism
160
What is Glucose-6-phosphate dehydrogenase deficiency?
X linked recessive disorder
161
What race is more likely to have G6PD deficiency and why?
African Americans. Increased malarial resistance
162
What is G6PD?
Rate limiting enzyme in HMP shunt (which yields NADPH)
163
What does decreased NADPH lead to?
hemolytic anemia, due to poor RBC defense agains oxidizing agents and antituberculosis drugs
164
What are Heinz bodies?
altered hemoglobin precipitates within RBCs - seen in G6PD deficiency
165
What are bite cells?
Result of phagocytic removal of Heinz bodies from macrophages
166
What is SCID?
severe combined immunodeficiency (aka bubble boy syndrome!)
167
Prevalence of SCID?
1 in 100,000 births
168
What populations have a higher incidence of SCID?
Australia and Navajo population
169
Which cell divisions are nonfunctional in SCID?
B cell AND T cell divisions of adaptive immune system
170
What are the 2 most common types of SCID?
X linked SCID (most common) and adenosine deaminase deficiency (2nd)
171
What is X-SCID due to?
X linked mutation
172
What percentage of SCID cases are X linked?
46-70%
173
What is the functionally defective gene in X-SCID?
IL 2 receptor which promotes lympocyte growth and differentiation
174
When is X-SCID fatal?
Usually in the first years of life
175
What is candidiasis?
thrush
176
When is candidiasis seen?
in X-SCID - can involve many body areas. More commonly seen with AIDS
177
What is Lesch-Nyhan syndrom?
X linked recessive disorder - purine salvage deficiency
178
What is Lesch-Nyhan syndrome due to?
absence of HGPRT, which converts hypoxanthine to IMP and guanine to GMP
179
What does Lesch-Nyhan syndrome result in?
excess uric acid production
180
Findings in Lesch-Nyhan syndrome?
retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
181
What is adenosine deaminase deficiency?
AUTOSOMAL RECESSIVE disorder - purine salvage deficiency, etiology for SCID
182
What percentage of SCID cases are due to adenosine deaminase deficiency?
15%
183
What was the first disease to be treated by experimental human gene therapy?
adenosine deaminase deficiency
184
What do excess ATP and dATP imbalances do to DNA synthesis, and what does this cause?
PREVENTS DNA synthesis => decreases lymphocyte count
185
What determines the age of onset and severity of adenosine deaminase deficiency?
Depends on 29+ genotypes
186
What is Duchenne's muscular dystrophy?
X linked recessive disease
187
What is Becker's muscular dystrophy?
X linked recessive disease
188
What do DMD and BMD result from?
Mutation in DYSTROPHIN gene
189
Which is more severe - DMD or BMD?
DMD - NO FUNCTIONAL DYSTROPHIN IS PRODUCED
190
What does insufficient dystrophin result in?
instability in structure of muscle cell membrane -> accelerates muscle breakdown
191
Multifactorial inheritance traits/processes?
Height, intelligence, BP, metabolism, development
192
Multifactorial inheritance diseases?
dwarfism, mental retardation, hypertension, diabetes mellitus, gout, anencephaly, cleft lip/palate
193
What type of inheritance is DM type 2?
MULTIFACTORIAL
194
Incidence of DM type 2?
50% of affected persons have relatives w/ diabetes
195
Which populations have high incidence of DM type 2?
Populations w/ high rate of intermarriage (ex. Pima Indians)
196
Is there high concordance of DM type 2 among monozygotic twins?
YES
197
How are X linked dominant traits inherited?
Through both parents
198
Which sex is affected with X linked dominant trait from affected MOTHER?
BOTH sexes MAY be affected
199
Which sex is affected with X linked dominant trait from affected FATHER?
ALL FEMALE OFFSPRING ARE AFFECTED
200
Examples of X linked dominant disorders?
Factor VIII (hemophilia A), Factor IX (hemophilia B), hypophosphatemic rickets
201
3 causes of prematurity?
Maternal factors (alcohol, smoking) Fetal factors (congenital abnormalities) Placental factors (location, viability)
202
What causes Neonatal Respiratory Distress Syndrome?
immature type II pneumocytes - surfactant deficiency
203
What does NRDS cause?
atelectasis, alveolar and endothelial injury of lungs.
204
Where does NRDS cause hypoxia?
hyaline membranes around alveoli
205
Complications from NRDS?
cerebral intraventricular hemorrhage, hemorrhagic intestinal necrosis
206
Possible types of birth injury? (5)
Mechanical trauma, skull fractures, intracranial hemorrhage, peripheral nerve injury, fractures of long bones of extremities
207
What causes Sudden Infant Death Syndrome?
Unknown
208
What is the most common cause of death in infants beyond immediate neonatal period?
SIDS
