Genetic and Congenital Disorder Flashcards
1
Q
What are the 4 main stages of prenatal development?
A
- Pre-implantation embryonic stage.
- Germ layer formation.
- Early organogenesis.
- Definite organogenesis.
2
Q
What is a congenital defect?
A
condition someone is born with.
3
Q
What are the different types of congenital defects and what are the % they make up?
A
75% - is unknown causes. 20% - genetic diseases. 2% - chromosomal abnormalities. 2% - infections. 1% - chemicals.
4
Q
What is a teratogen?
A
Environmental agent that interrupts the normal development of an organism
5
Q
What are the three classifications of exogenous teratogens?
A
1) Physical teratogen
2) Chemical teratogen
3) Microbial teratogen
6
Q
Give 3 examples of a physical teratogen?
A
1) x-ray
2) corpuscular radiation(alpha, beta, gamma rays)
3) A bomb.
7
Q
What type of teratogen is thalidomide and what does it cause?
A
It is a chemical teratogen that lead to babies being born with phocomelia (flipper-like arms or legs).
8
Q
What was thalidomide prescribed for?
A
Preventing morning sickness.
9
Q
What type of teratogen would viruses, bactria, protozoal parasites be?
A
Microbial teratogens.
10
Q
What is FASD’s?
A
Fetal alcohol spectrum disorders.
11
Q
What are some symptoms of FASD’s?
A
1) Small for gestational age
2) Small eye openings
3) Poor coordination
4) Hyperactive behavior
5) Learning disabilities
6) Developmental disabilities (speech and language delays)
7) Low IQ
8) Poor reasoning and judgement skills
9) Sleep and sucking disturbances in infancy.
12
Q
What is TORCH(ES) syndrome?
A
a medical acronym for a set of perinatal infections (i.e. infections that are passed from a pregnant woman to her fetus).
13
Q
When should we test for TORCH(ES) syndrome?
A
Early in pregnancy.
14
Q
What will the T in Torches syndrome stand for and how do we get it?
A
Toxoplasma we get it from cat shit so stay away from Julie.
15
Q
What will the O in TORCHES syndrome stand for?
A
Others that are less common like Epstein-Barr virus, Varicella virus, Listeria monocytogenes, leptospira.
16
Q
What will the R in TORCHES syndrome stand for?
A
Rubella.
17
Q
What will the C in TORCHES syndrome stand for?
A
Cytomegalovirus (CMV).
18
Q
What will the H in TORCHES syndrome stand for?
A
Herpesvirus.
19
Q
What will the (ES) in TORCH(ES) syndrome stand for?
A
Syphylis.
20
Q
What does rubella cause?
A
1) Small (microcephaly)/strucuraly abnormal brain
2) Heart defects.
21
Q
What will Toxoplasma cause?
A
1) Microcalcification of basal ganglia and dilation of lateral ventricles (hydrocephalus)
2) CNS defects.
22
Q
What will cytomegalovirus (CMV) cause?
A
The same as Toxoplasma.
23
Q
What will herpesvirus affect?
A
1) CNS defects
2) Skin lesions.
24
Q
What are 2 types of chromosomal anomalies?
A
Structural and numerical anomalies
25
What is Aneuploidy?
Loss or gain of chromosomes.
26
What are 2 types of aneuploidy?
Hyperdiploidy- 46+1 or 46+2.
| Hypodiploidy- 46-1 or 46-2.
27
What is monosomy?
Missing one chromosome
28
What is Trisomy?
Gaining an extra chromosome (3 of one chromosome)
29
What is the most common risk factor for Down syndrome?
Paternal age increases risk of having a baby born with down syndrome
30
What disorder is associated with Down syndrome?
Trisomy 21 (D= drinking age 21)
31
What disorder is associated with Edward's syndrome?
Trisomy 18 (E = election age 18)
32
What disorder is associated with Patau's syndrome?
Trisomy 13 (P = puberty age 13)
33
Of the 3 disorders Down, Edward's and Patau's, which one is most common?
Down Syndrome
34
What happens to a baby's hands with down syndrome?
Simian crease.
35
Down syndrome or trisomy 21 leads to what mental issues?
Most commonly leads to mental retardation
36
How will down syndrome affect the head?
Flat facial profile and epicanthic folds
37
How will down syndrome affect the heart?
Congenital heart defects like septum primum due to endocardial cushion defects.
38
How will down syndrome affect the limbs and feet?
Hypotonia
| A gap between first 2 toes.
39
What is the life expectancy with edwards sydnrome aka trisomy 18?
less than 1 year.
40
What will edwards syndrome cause?
Severe mental retardation.
41
How will edwards syndrome affect the head?
1) Prominent occiput
2) micrognathia (small jaw)
3) low set ears.
42
How will Down syndrome affect the umbilicus and intestines?
Causes umbilical hernia and intestinal stenosis
43
What is the incidence of down syndrome?
1 in 700 births
44
How will edwards syndrome affect the heart?
Congenital heart defects will be present.
45
How will edwards syndrome affect the hands and feet?
Hands- Clenched hands
| Feet- Rocker-bottom feet.
46
What is the life expectancy with down syndrome?
45-50 years old
47
What is the incidence of Edward's syndrome?
1 in every 8000 births
48
What some limb changes with Edward's symptoms
Limited hip abduction
| Rocker bottom feet
49
What is the incidence of Edward's syndrome?
1 in 8000
50
What are some neurological issues with patau symptoms?
Microcephaly and mental retardation
51
What are some head changes with patau symptoms?
Cleft lip and palate
| Microphthalmia
52
What are some limb issues with patau symptoms?
1) Polydactylyl
| 2) Focker -bottom feel
53
What is the incidence of Patau syndrome?
1 in 15000
54
What is the life expectancy of Down syndrome?
45-50
55
What is the life expectancy of Edwards syndrome?
<1 year
56
What is the life expectancy of Patau syndrome?
<1 year
57
In which disorder(s), (Downs, Edwards, Patau) does mental retardation occur?
Yes, severe in Edwards and Patau
| and the most common cause is Down Syndrome
58
What are some other disease risks for Down Syndrome?
ALL, Alzheimer's >age 35
59
What are two disorders that are caused by abnormalities of sex chromosomes?
1) Turner syndrome
| 2) Klinefelter syndrome
60
Who can get turner's syndrome and who can get Klinefelter's syndrome?
They are abnormalities of sex chromosomes so only females can get Turners and Only males can get Klinefelter's syndrome.
61
Pathogenesis of sex chromosome abnormalities are due to what?
Nondisjunction.
62
What is nondisjunction?
Failure of paired chromosome to separate.
63
How common is Turners syndrome?
1 in every 3,000 female births.
64
What are the symptoms of Turners syndrome? (It's super long, sorry)
1) Short stature
2) heart- shaped face
3) low posterior hairline
4) webbing of neck
5) heart disease and coarctation of aorta
6) broad chest and widely spaced nipples
7) pigmented nevi (moles)
8) cubitus valgus(elbows turned in)
9) streak ovaries, hypoplastic uterus, amenorrhea
10) peripheral lymphedema at birth.
65
Are Turner's considered male or female?
Female presentation
66
What symptoms will Klinefelter's syndrome present with?
1) Tall long arms and legs
2) lack of beard body hair and pubic hair
3) gynecomastia
4) female like hips
5) testicular atrophy.
67
Is Klinefelter syndrome considered male or female?
Male presentation (based on penis presentation)
68
What is mendelian inheritance?
a set of primary principles relating to the transmission of hereditary characteristics from parent organisms to their offspring
69
What is heterozygotes and homozygotes?
Hetero - a particular gene pair will be different. Homo - the gene pair will be the same.
70
What are alleles?
Genes expressed in duplicate
71
What is the difference between autosomal dominant and autosomal recessive?
1) Recessive- a genetic condition that only appears in people that have both pairs of an autosomal(a non sex chromosome) gene.
2) Dominant- A genetic condition that appears in people that have 1 normal gene and 1 autosomal gene.
72
What is mitochondrial inheritance?
The inheritance of a trait encoded in the mitochondrial genome
73
With an autosomal dominant inheritance will the trait be apparent in heterozygotes?
yes.
74
In many cases when will mendelian inheritance present clinically?
After puberty.
75
What is critical in diagnosing a mendelian inheritance?
Family history.
76
What % will an affected heterozygote (autosomal dominant) have of transmitting the gene to offspring?
50%.
77
What % will an affected homozygote (autosomal dominant) have of transmitting the gene to offspring?
100%.
78
What % of children from parents who are both heterozygote (autosomal dominant). will be affected?
1) 25% will be homozygote.
2) 50% will be heterozygote,
3) 25% will be uneffected.
79
What is an autosomal dominant disease that affectes connective Tissue?
Marfan's Syndrome
80
What is the clinical presentation of someone with Marfan's syndrome?
1) Elongated hands
2) eye abnormalities
3) aortic aneurysm
4) floppy mitral valve
5) vertebral deformity
6) Long fingers (arachnodactyly)
81
How is Marfan's syndrome inherited?
It is an autosomal dominant inheritance.
82
Marfan's syndrome is a molecular defect of what?
mutation in the gene encoding the glycoprotein Fibrillin-1 (FBN1).
83
What is FBN1 involved in?
Main componenet of microfibrils and helps anchor cells to the ECM therefore causes connective tissue anomalies when absent
84
With marfan's syndrome what are the principle structures that are defective?
Cardiovascular, musculoskeletal, ocular.
85
Besides the CV, MS and ocular areas, what else is effected by marfan's syndrome?
Pulmonary and CNS.
86
Marfan's syndrome is typically recognized by what?
Long limbs, aortic root dilation and dislocated lenses.
87
What happens with teenagers who have marfan's syndrome?
kyphoscoliosis, pectus excavatum, genu recurvatum (knee has > 5 degree extension)
88
Achondroplastic dwarfism is what?
An autosomal dominant inherited bone disease.
89
Which is the most common type of dwarfism and what are the signs and symptoms?
Achondroplastic dwarfism (AKA Jim Dietrich Disorder) is the most common and it presents with:
1) Bulky forehead
2) saddle nose
3) lumbar lordosis
4) bowlegs.
90
What is the defective gene product that causes achondroplastic Dwarfism?
Fibroblast growth factor (FGF) receptor 3
91
What kind of disorder is Osteogenesis imperfecta ?
A hereditary collagen disorder
92
What clinical presentation does he collagen disorder of osteogenesis imperfecta present with?
1) abnormal fragility of bone
2) hearing loss, blue sclerae (seen with all collagen disorders)
3) dentinogenesis imperfecta
4) joint hypermobility.
93
How many types of osteogenesis imperfecta are there?
I-IV.
94
What types of osteogenesis imperfecta are caused by autosomal dominant inheritance and what cause the other types?
1) I and IV are autosomal dominant.
| 2) II and III are autosomal recessive.
95
How common is Hearing loss with osteogenesis imperfecta?
50-65%.
96
Of the 4 types of osteogenesis imperfecta rank them from mildest to most severe?
I-mildest < IV- intermediate in severity < III- most severe nonlethal form < II- most severe and lethal.
97
What clinical presentations are found with Type I osteogenesis imperfecta?
1) Blue sclera (d/t a deficiency in CT allowing underlying vessels to show through)
2) joint hypermobility leading to musculoskeletal pain
3) recurrent fractures in childhood are possible.
98
What clinical presentations are found with Type II osteogenesis imperfecta?
1) Blue sclera
2) shortened extremities due to multiple congenital fractures
3) skull is soft and feels like a bag of bones
4) Trauma during delivery may cause intracranial hemorrhage and stillbirths.
99
What clinical presentations are found with Type III osteogenesis imperfecta?
1) Short stature
2) spinal curvature and multiple
3) recurrent fractures
4) Macrocephaly with triagular facies
5) pectal deformities are common
6) hearing loss is possible
100
What clinical presentations are found with Type IV osteogenesis imperfecta?
1) Bones fracture easy in childhood before adolescence
2) Sclera normal color
3) moderate-short height.
101
What type of Osteogenesis imperfecta may benefit from treatment?
Type IV.
102
What is the survival rate like with osteogenesis imperfecta type IV?
survival rate is high.
103
With osteogenesis imperfecta which adult arm bones were defective in the x-ray he showed us?
Radius and ulna.
104
Blue sclera is associated with osteogenesis why?
Blue sclera is associated with connective tissue disorders and osteogenesis imperfecta is a collagen disorder.
105
Blue disoloration of the sclera happens when?
thinning of the sclera allows the underlying choroid to become visible.
106
What is elevated with familial hypercholesterolemia?
LDL.
107
Why will LDL be elevated with familial hypercholesterolemia?
Defective or absent LDL receptor.
108
What will cholesterol levels of heterozygote and homozygote familial hypercholesterolemia patients have?
1) Hetero- 300mg/dl.
| 2) Homo-700+ mg/dl.
109
Homozygotes with familial hypercholesterolemia develop what in early life?
Tendon xanthomas (tumor of lipid foam cells) classically seen in the achilles tendon.
110
What may develop with homozygotes with familial hypercholesterolemia by age 20?
MI.
111
What is the Liver's role with LDL?
It is involved with synthesis and clearance.
112
There are 5 different classes of LDL receptor mutations and all of them are what?
Heterogeneous at the DNA level.
113
What should be taken to help with familial hypercholesterolemia and what are its 2 names?
Nicotinic acid aka Vitamin B3.
114
What effects will nicotinic acid and Vitamin B3 have on hypercholesterolemia?
Increases HDL and lowers TG and LDL.
115
What are the adverse effects of nicotinic acid (vitamin B3)?
1) Flushing
2) impaired glucose tolerance
3) increased uric acid.
116
What can be given with nicotinic acid to help with adverse effects?
Aspirin and given with food.
117
What type of diet can help lower cholesterol and how?
High fiber by binding to cholesterol before it can be reabsorbed in the liver.
118
What type of drugs are given to help lower cholesterol?
Statins.
119
What is PKD?
Polycystic kidney disease it is an autosomal dominant or recessive disease that affects the kidney.
120
What are the 2 forms of PKD and what causes them?
Adult- autosomal dominant.
| Juvenile- autosomal recessive.
121
How common is the adult form or Autosomal dominant PKD?
1/1000 people.
122
Autosomal dominant PKD accounts for what % of patients with end-stage renal disease requiring replacement therapy?
5-10%.
123
Clinical manifestations of PKD happen when?
Rare before adulthood, but essentially all patients by 80 years of age or older.
124
How common is autosomal recessive PKD or the child form?
1/10,000 people.
125
PKD is associated with what?
Polycystic liver disease, berry aneurysms mitral valve prolapse.
126
What are berry aneurysms?
A small saccular aneurysm of a cerebral artery that resembles a berry.
127
86-96% of ADPKD (autosomal dominant PKD) cases are caused by what?
mutations in the PKD1 gene on chromosome 16.
128
What will the PKD1 gene on chromosome 16 code for?
Polycystin 1 protein.
129
What other things can cause ADPKD besides mutations of the PKD1 gene on chromosome 16?
PKD2 gene on chromosome 4.
130
What will the PKD2 gene on chromosome 4 code for?
Polycystine 2 protein.
131
What will polycystin 1 and polycystin 2 do?
1) epithelial cell adhesion and differentiation
| 2) function as anion channel.
132
Mutations of the polycystin proteins leads to what?
Renal cilia function alterations.
133
What will altered renal cilia lead to?
Flow rate issues that lead to cystic transformation.
134
What is the prognosis of PKD?
by age 75 50-75% of patients will need a renal replacement therapy (dialysis or transplantation).
135
What are the treatments for PKD?
Strict BP control and limits to protein intake of .6-.7 g/kg/day.
136
Can PKD happen on just one side?
No it is bilateral always.
137
What type of disorder is spherocytosis?
A congenital RBC membrane disorder. IT is an autosomal dominant disease.
138
What are 3 possible symptoms of spherocytosis?
anemia, jaundice, splenomegaly.
139
How is spherocytosis diagnosed?
requires demonstration of increased RBC osmotic fragility and negative direct antiglobulin test.
140
How often will spherocytosis patients less than 45 years old need a splenectomy?
Rarely.
141
With spherocytosis what causes RBC abnormalities?
Alterations in membrane proteins.
142
What alternations in membrane proteins of RBC happens with spherocytosis?
Surface area is decreased disproportionately to the intracellular content.
143
What will decreased surface area of a RBC membrane cause?
Flexibility needed for the cell to traverse the spleen's microcirulation.
144
With western treatments how will spherocytosis be cured?
Splenectomy.
145
Presence of spherocytes in the peripheral blood smear suggest what?
1. Hereditary spherocytosis (HS).
| 2. Autoimmune hemolytic anemia (AIHA).
146
When there are spherocytes in the peripheral blood smear how can you distinguish between hereditary spherocytosis or autoimmune hemolytic anemia?
Coomb's test.
147
What will a negative and positive Coomb's test mean?
Negative- Hereditary spherocytosis.
| Positive- Autoimmune hemolytic anemia.
148
Huntington's disease is what type of disorder?
An autosomal dominant characterized by chorea and progressive cognitive deterioration.
149
How will Huntington's disease be diagnosed?
Genetic testing.
150
What is treatment of Huntington's disease like?
Supportative.
151
What type of relatives of patients with Huntington's disease should be tested?
first-degree relatives.
152
Will Huntington's disease effect males or females more?
Both equal.
153
What parts of the CNS will Huntington's disease effect?
Caudate nucleus atrophies, medium spiny neurons in the corpus striatum degenerate, and levels of neurotransmitters gamma aminobutyric acid and substance P decrease.
154
What genes are effected with Huntington's disease?
Gene on chromosome 4.
155
The gene on chromosome 4 (Huntington's disease) will lead to what?
Abnormal repetition of DNA sequence CAG that codes for amino acid Glutamine.
156
The gene product of abnormal CAG codes that make glutamine leads to what?
a large protein called huntingtin and it has large stretches of polyglitamine residue.
157
How will the huntingtin protein lead to huntington's disease?
Unknown.
158
The more CAG repetitions means what?
The earlier the disease begins and the more severe the effects.
159
What will huntington's disease be like from generation to generation?
over time it leads to more severe phenotype and more CAG codes that make more polyglitamine residues.
160
How do Symptoms of Huntington's disease develop?
Insidiously (inconspicuous or seemingly harmless way ).
161
When do Signs and symptoms of Huntington's disease develop?
start between 35-50, but can develop before adulthood.
162
What are the signs and symptoms of Huntington's disease?
Dementia or psychiatric disturbances, abnormal movements including tongue protrusion.
163
Death usually occurs how long after the first signs and symptoms of Huntington's disease appear?
13-15 years.
164
What will the cause of death usually be with Huntington's disease?
Coronary heart disease or pneumonia
165
What are the Trinucleotide repeat expansion diseases?
1) Huntington's
2) Myotonic dystrophy
3) Friedreich's ataxia
4) Fragile X syndrome.
166
With trinucleotide repeat expansion diseases what can be anticipated?
In each successive generation the disease severity increases and age of onset decreases. This is known as genetic anticipation.
167
What is Autosomal recessive inheritance of trinucleotide repeat expansion diseases often due to?
Enzyme deficiencies.
168
In how many generations are Autosomal recessive inheritances of trinucleotide repeat expansion diseases often seen?
only 1 generation.
169
What is more severe autosomal recessive inheritance or autosomal dominant inheritance for trinucleotide repeat expansion diseases?
Recessive.
170
When do Autosomal recessive inheritance of trinucleotide repeat expansion disease patients present with disease?
Childhood.
171
Name 2 amino acid disorders that are autosomal recessive inherited trinucleotide repeat expansion disease?
phenylkeonuria, and albinism.
172
Name 2 anemias that are autosomal recessive inherited trinucleotide repeat expansion disease?
thalassemias, sickle cell anemia.
173
What is the most common and leathal genetic disease of caucasians?
Cystic Fbrosis.
174
What are the different types of autosomal recessive disorders?
1) Cystic fibrosis
2) Amino acid disorders
3) Anemias
4) Hemochromatosis
5) alpha1 - antitrypsin deficiency
6) glycogen storage diseases
7) Lysosomal storage diseases
8) Infant polycystic kidney diseases
175
What gene is effected with cystic fibrosis?
Autosomal -recessive defect in CFTR gene on chromosome 7.
176
What will the CFTR gene on chromosome 7 do?
Creates a CFTR channel that actively secretes Cl- from the lungs and GI tract and it actively reabsorbs cl- from sweat.
177
Why will cystic fibrosis cause infertility in males?
bilateral absence of vas deferens.
178
Why will cystic fibrosis present as a failure to thrive in infancy?
Fat-soluble vitamin (ADEK) deficiencies.
179
What is the treatment of cystic fibrosis?
N-acetylcysteine.
180
What will N-acetylcysteine do?
Loosen mucous plugs.
181
Name a way to determine if someone has cystic fibrosis?
Positive sweat test.
182
With cystic fibrosis we get abnormal chloride transport that leads to what?
Viscous mucus.
183
Viscous mucus affects what 3 areas?
Pancreas, fetal intestines, Bronchi.
184
How will viscous mucus affect the pancreas?
Malabsorption -> malnutrition -> Can lead to death.
185
How will viscous mucus affect the fetal intestines?
Merconium ileu -> merconium pertonites -> Leads to death.
186
How will viscous mucus affect the bronchi?
Bronchitis -> bronchetasis -> recurrent pneumonia -> death.
187
What is tested for in the sweat test?
High concentration of Cl- ions.
188
What is the pathogenesis of cystic fibrosis?
Defective Cl- channel -> secretion of abnormally thick mucus that lugs lungs, pancreas and liver -> recurrent pulmonary infections, chronic bronchitis, bronchiectasis, pancreatic insufficiency and meconium ileus in newborns
189
Cystic fibrosis has an affected CFTR gene on chromosome 7 that results in a protein that is missing what?
amino acid 508(phenylalanine).
190
Will there be a frameshift with the cystic fibrosis disease?
No because the deletion was 3 so no frameshift mutation occurs.
191
Who does sickle cell anemia chronic hemolytic anemia occurs almost exclusively to?
Blacks.
192
Sickle cell anemia is caused by what?
homozygous inheritance of Hb S.
193
What do Sickle-shaped RBC that clog capillaries cause?
Organ ischemia.
194
What type of pain may develop with sickle cell anemia?
Acute pain may develop frequently.
195
How will sickle-cell anemia be fatal?
Infection, bone marrow aplasia, or lung involvment.
196
What makes Hb S different and a problem in sickle-cell anemia?
Valine is substittuted for Glutamic acid in the 6th amino acid of the beta chain.
197
What causes RBC's to deform with sickle cell anemia?
oxygenated Hb S is less soluble than oxygenated Hb A. So oxygenated Hb S forms a semisolid gel that causes RBC to deform in a sickle chape at sites of low P02
198
What do distorted RBCs do?
Adhere to vascular endothelium and plug small arterioles and capillaries leading to infarction.
199
What will deform bones with sickle-cell anemia?
chronic compensatory marrow hyperactivity.
200
What type of mutation takes place with sickle-cell anemia?
A point mutation.
201
what type of disease is sickle-cell anemia?
Autosomal recessive inheritance.
202
What causes Lysosomal storage diseases?
An autosomal recessive disorder where one or more of the enzymes needed to degraded something in a lysosome is absent leaving a soluble end product.
203
What happens if there is a deficiency of just one of the lysosomal enzymes?
Catabolism is incomplete and insoluble intermediates accumulate in the lysosomes.
204
Name 2 lysosomal diseases that are not Autosomal recessive inheritance?
Fabry's and hunter's disease.
205
What lysosomal storage disease can be characterized by progressive neurodegeneration, hepatosplenomegaly, Cherry-red spots foam cells?
Niemann-pick disease.
206
What is the deficient enzyme with niemann-picks disease?
Sphingomyelinase.
207
What substrate is accumulated with niemann-picks disease?
Sphingomyelin.
208
What is Tay-sachs disease characterized by?
Progressive neurodegeneration, developmental delay, cherry-red spot, lysosomes with onion skin.
209
What is the deficient enzyme with tay-sachs disease?
Hexosaminidase A.
210
What substrate is accumulated with Tay-sachs disease?
GM2 ganglioside.
211
What is the most common lysosomal storage disease?
Gaucher's disease.
212
What are the characteristics of Gaucher's disease?
Hepatsplenomegaly, asecptic necrosis of femur, bone crises, Gaucher's cells look like crumpled tissue paper.
213
What is the deficient enzyme with Gaucher's disease?
Beta-glucocerebrosidase.
214
What is the substrate that accumulates with Gauchers disease?
Glucocerebroside.
215
What are the characteristics of Fabry's disease?
Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease
216
What is the deficient enzyme with Fabry's disease?
alpha-galactosidase A
217
What is the substrate that accumulates with Fabry's disease?
Ceramide trihexoside
218
What are the characteristics of Krabbe's disease?
Periheral neuropathy, developmental delay, optic atrophy, globoid cells
219
What is the deficient enzyme with Krabbe's disease?
Galactocerebrosidase
220
What is the substrate that accumulates with Krabbe's disease?
Galactocerebroside
221
What are the characteristics of metachromatic leukodystrophy?
Central and peripheral demyelination with ataxia, dementia
222
What is the deficient enzyme with metachromatic leukodystrophy?
Arylslfatase A
223
What is the substrate that accumulates with metachromatic leukodystrophy?
Cerebroside sulfate
224
What are the characteristics of Hurler's syndrome?
Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
225
What is the deficient enzyme with Hurler's syndrome?
alpha-L-iduromidase
226
What is the substrate that accumulates with Hurler's syndrome?
Heparan sulfate, dermatan sulfate
227
What are the characteristics of Hunter's syndrome?
Mild Hurler's and aggressive behavior, no corneal clouding
228
What is the deficient enzyme with Hunter's syndrome?
Iduronate sulfatase
229
What is the substrate that accumulates with Hurler's syndrome?
Heparan sulfate, dermatan sulfate
230
What lysosomal storage disease has concentric rings of the membrane?
Tay-sachs disease.
231
What type of mutation is Tay-sachs disease and who will it affect?
Frameshift mutation, Ashkenazi jews.
232
What organ is Niemann-Picks disease found in?
The liver.
233
What liver cells are affectd by niemann-picks disease? How are they affected?
Hepatocytes and Kupffer cells have a foamy vacuolated appearance owing to deposition of lipids.
234
What is PKU and it is most common among who?
Phenylketonuria, most common in all white people, and relatively less common among ashkenazi jews, chinese, and blacks.
235
How common is PKU among whites?
1/10,000 births.
236
PKU will have excess dietary phenylalanine that will do what?
Be converted to tyrosine.
237
What will convert phenylalanine into tyrosine?
Phenylalanine hydroxylase.
238
What is the essential cofactor for phenylalanine hydroxylase to convert phenylalanine into tyrosine?
Tetrahydropbiopterine (BH4).
239
What causes PKU?
When one of the several gene mutations results in deficiency or absence of phenylalanine hydroxylase.
240
With a deficiency or absence of phenylalanine hydroxylase large amounts of phenylalanine accumulate and cause what?
accumulations in the brain, and some is metabolized into phenylketones and are excreted in the urine.
241
What are the clinical symptoms of PKU?
Mental retardation with cognitive and behavioral abnormalites. Also growth retardation, fair skin, eczema, and musty body odor.
242
The primary cause of PKU is a deficient phenylalanine hydroxylase, but what is another cause of PKU?
Decreased tetrahydrobiopterine the cofactor.
243
When and how will PKU be tested?
At birth they check for high phenylalanine levels and normal or low tyrosine levels.
244
What will cause the musty body odor associated with PKU?
The abnormal metabolism of a AROMATIC amino acid.
245
What is the treatment for PKU?
Lifelong dietary phenylalanine restriction, and increased tyrosine in diet.
246
What is the prognosis of PKU with treatment?
Excellent.
247
How are glycogen storage diseases acquired?
They are autosomal recessive disorders.
248
What is the myocardium like with pompe's disease?
Normal with abundent eosinophilic cytoplasm.
249
What is a X-linked recessive disorder?
A genetic disorder of the X chromosome.
250
Sons of heterozygous mothers have what chance of being affected with an X-linked recessive disorder?
50%
251
Sons of heterozygous fathers have what chance of being affected with an X-linked recessive disorder?
None
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X-linked recessive disorders affect females or males more?
Males.
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What is the acronym for remembering the X-linked recessive disorders?
Be WIse, FooL's GOLD Heeds False Hope.
254
What are the findings with von gierke's disease?
Severe fastng hypoglycemia, Increased glycogen in liver, increased blood lactate, and hepatomegaly.
255
What are the findings with pompe's disease?
Cardiomegaly and systemic findings leading to early death.
256
What are the findings with cori's disease?
Milder than type I aka con gierke's disease. The blood lacate levels are normal, and gluconeogenesis is intact.
257
What are the findings with McArdles disease?
Increased glycogen in muscles, but can't break it down, leading to painful muscle cramps.
258
In which gender are x-linked recessive disorders more severe?
Males
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With x-linked recessive disorders, would heterozygous or homozygous females be affected? Which will express the phenotype?
Heterozygous females = may be affected
| Homozygous females = express phenotype
260
What does the B in the acronym (Be Wise, FooL's GOLD Heeds False Hope) stand for?
Bruton's agammaglobulinemia (congenital immunodeficiency)
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What does the W in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
Wiskott-aldrich syndrome
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What does the I in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
Immunodeficiency (X-SCID)
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What does the F in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
Fragile X syndrome.
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What does the first L in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
Lymphoproliferative disorders (Duncan's syndrome)
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What does the G in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
G6PD deficiency
266
What does the O in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
Ocular albinism
267
What does the 2nd L in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
Lesch-Nyhan syndrome
268
What does the D in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
Dystrophies: (Duchenne's and Becker's muscular dystrohy)
269
What does the first H in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
Hemophilia A and B
270
What does the F in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
Fabry's disease
271
What does the 2nd H in the acronym (Be WIse, FooL's GOLD Heeds False Hope) stand for?
Hunter's syndrome
272
What will fragile X syndrome affect?
Methylation and expression of the FMR1 gene.
273
What is Fragile X statistically known for?
The most common mental retardation in males and second overall genetic retardation after Downs.
274
Fragile X will clinically present as what?
Macro-orchidism, long face with large jaw, large everted ears, autism.
275
What usually happens to females that get X-linked recessive disorders?
They are usually silent carriers.
276
What % of females that inherit the full mutation of an X-linked recessive disorder are affected?
50% and the effect is mild.
277
What causes glucose-6-phosphate dehydrogenase deficiency?
X-linked recessive disorder.
278
A glucose-6-phosphate dehydrogenase deficiency is most common among who and it will cause what?
Among Black and it increases the resistance to malaria.
279
Glucose-6-phosphate dehydrogenase deficiency besides resistance to malaria will cause what to happen?
The glucose-6-phosphate dehydrogenase enzyme is the rate limiting enzyme in the HMP Shunt, and not having enough of this enzyme leads to decreased NADPH in RBC and this leads to HEMOLYTIC ANEMIA (which is anemia due to destruction of erythrocytes).
280
Glucose-6-phosphate dehydrogenase deficiency leads to altered hemoglobin precipitates within RBC and these precipitates of Hemoglobin are known as what?
Heinz bodies.
281
With Glucose-6-phosphate dehydrogenase deficiency phagocytes remove the heinz bodies and make the RBC look different and they are known as what?
Bite cells.
282
What is SCID?
Severe combined immunodeficiency.
283
What is SCID also known as?
Boy in the Bubble syndrome.
284
SCID is most common among who?
Navajo populations.
285
What will SCID do to the body?
Due to one of several gene defects both B and T cell division of adaptive immune system are non-functional.
286
What is the most common gene defect that causes SCID?
X-linked severe combined immunodeficiency (X-SCID).
287
What is the second most common gene defect that causes SCID?
Adenosine deaminase deficiency.
288
X-SCID has what defected gene?
IL2 receptor on the X chromosome because it is an X chromosome disorder.
289
What will the IL2 gene do?
Promotes lymphocyte growth and differentiation.
290
X-SCID is usually fatal after how long?
firsts years of life.
291
X-SCID can cause candidiasis which is what and it is associated with what?
an infection caused by fungus that affects the skin, mouth, respiratory tract, and vagina. It is associated with AIDS a lot of the time.
292
Lesch-Nyhan syndrome is caused by what?
A purine salvage deficiency. It is an X-linked recessive disorder.
293
Lesch-nyhan syndrom has a purine salvage deficiency that leads to what?
Excess uric acid production.
294
What are the clinical signs of Lesch-nyhan syndrome?
retardation, self-mutilation, aggression, hyperuricemia, gout, and choreoathetosis.
295
Adenosine deaminase deficiency is caused by what?
Autosomal recessive inheritance not X-linked recessive inheritance.
296
What is happening in the body with adenosine deaminase deficiency?
It is also a purine salvage deficiency.
297
Adenosine deaminase deficiency is an etiology for what?
SCID.
298
What will decrease Lymphocyte count with adenosine deaminase deficiency?
Excess ATP and dATP imblanaces nucleotide pool via feedback inhibition of ribonucleotide reductase and this prevents DNA synthsis and thus decrease the lymphocyte count.
299
Adenosine deaminase deficiency was the first disease to be treated by what?
Experimental human gene therapy.
300
What is the age of onset for adenosine deaminase deficiencies?
All ages from infancy, childhood, adolescence, or adulthood and the severity depends on 29 known genotypes
301
What are the 2 dystrophies that are related to x-linked recessive diseases?
1. DMD (Duchenne's muscular dystrophy).
| 2. BMD (Becker's muscular dystrophy).
302
Both DMD and BMD result from what X chromosome gene mutation?
dystrophin gene.
303
Which is more severe DMD or BMD?
DMD.
304
Insufficient dystrophin results in what?
instability in structure of muscle cell membrane and accelerates muscle breakdown.
305
How tall are People with dystrophies and is their intelligence affected?
Experience dwarfism and mental retardation.
306
What will metabolism be like for people with dystrophies?
Carbohydrates is bad and leads to DM,
| Uric acid is bad and leads to Gout.
307
What are the developmental problems with dystrophies?
Cleft lip or palate.
308
What % of people with DM type II have family members with DM type II?
50%.
309
Who is the X-linked dominant transmitted through ?
Both parents.
310
With X-linked dominant diseases when the mother is the only parent with the disease she will affect who?
50% of males and 50% of females.
311
With X-linked dominant diseases when the father is the only parent with the disease he will affect who?
All females and none of the males.
312
In Type II DM in which populations is there a high incidence?
Those with a high rate of intermarriage (ie: Pima indians)
313
Is there a concordance of DM type II in monozygotic twins?
Yes there is a high concordance
314
What are 2 ways that prenatally we can test for X-linked dominant diseases?
1. Amniocentisis.
| 2. Chorionic Biopsy.
315
What went wrong with neonatal respiratory distress syndrome?
Immature pneumocytes Type II. Because of deficient surfactant.
316
What are the 3 factors that cause prematurity of a child?
```
Maternal factors (EtOH, smoking
Fetal factors (congenital abnormalities)
Placental factors (location and viability)
```
317
What are the complications with respiratory distress syndrome?
cerebral intraventricular hemorrhage, and hemorrhagic testicular necrosis.
318
What type of bones are fractured commonly during birth?
Skull, and Long bones of extermities.
319
What are some birth injuries that can occur?
```
Mechanical trauma
Skull fractures
intracranial hemorrhage
peripheral nerve injury
fractures of long bones of extremities
```
320
What is the cause of Sudden infant death syndrome (SIDS)?
Unknown
321
SIDS is the most common cause of death in what stage of infancy?
those beyond the immediate neonatal period.
