Biochem 2 Flashcards
(217 cards)
1
Q
ELISA stands for
A
Enzyme-linked immunosorbent assay
2
Q
Indirect ELISA
A
A test antigen used to determine if an antibody is in the patient’s blood, second antibody used to detect the first antibody.
3
Q
Direct ELISA
A
Test antibody used to detect antigen in patient’s blood, second antibody is used to detect the antigen
4
Q
Positive ELISA result
A
Lights up brightly
5
Q
Indirect ELISA test
A
anti-HIV antibody detection
6
Q
Fluorescent in situ hybridization.
A
Using fluorescent DNA or RNA probe to bind specific gene site of interest on chromosomes.
7
Q
Uses of FISH
A
Microdeletions that can’t be detected by karyotype
8
Q
Steps of cloning
A
Isolate euk. mRNA, use reverse transcriptase to make cDNA, insert cDNA into bacterial plasmids with ABx resistance genes, transform recombinant plasmid into bacteria, grow on Abx medium to get the bacteria that produces the cDNA.
9
Q
How to get DNA into a mouse
A
- Random insertion into mouse genome. 2. Trageted insertion or deletion of gene through homologous recombination with mouse gene.
10
Q
What is homologous recombination
A
Uses a complementary dsDNA template (like the other chromosome) to fix dsDNA breaks. Can also be used for cloning………
11
Q
Cre-lox system
A
Can induce genes at specific developmental points……………………………..
12
Q
RNA interference (RNAi)
A
dsRNA complementary to target mRNA used to degrade target mRNA
13
Q
What tissues can be karyotypes
A
blood, bone marrow, amniotic fluid, or placental tissue.
14
Q
alpha1-antitrypsin deficiency is inherited in what way
A
Codominance………….
15
Q
Neurofibromatosis type 1 inheritance
A
variable expressivity
16
Q
Example of pleiotropy
A
PKU with light skin, retardation, and musty body odor
17
Q
what diseases have anticipation
A
Huntington, fragile x, myotonic dystrophy
18
Q
Do oncogenes need loss of heterogeneity
A
No, loss of heterogeneity only applies to tumor suppression genes
19
Q
Explain dominant negative mutation
A
It’s a dominant mutation but it has the the negative, suppressive effect. Like a nonfunctional transcription factor preventing the functional wildtype protein from working.
20
Q
Linkage disequilibrium for individuals or population
A
Measured in a population, not in a family
21
Q
When is McCune-Albright a viable condition
A
Only if it is inherited mosaically
22
Q
What is McCune-Albright syndrome
A
Genetic syndrome with 2 out of 3 of following: autonomous endocrine excess (e.g. precocious puberty), polyostotic fibrous dysplasia, unilateral cafe au lait spots.
23
Q
What is locus heterogeneity
A
Mutations at different loci producing the same phenotype
24
Q
What is allelic heterogeneity
A
Different mutations in the same locus produce the same phenotype
25
Heteroplasmy
Having normal and mutated mtDNA, causes variable expression in mitochondrial inherited disease.
26
How is homologous recombination used in cloning
.....
27
Uniparental disomy
Receiving 2 copies of a chromosome from one parent. and 0 from the other.
28
Hetero vs. isodisomy
Hetero occurs in meiosis I, iso in meiosis II. Iso can also happen post-zygotically with a chromosomal duplication and loss of the other chormosome.
29
When to consider UPD
When an individual has a recessive disorder but only one parent is carrying the trait.
30
How bad is UPD usually
Usually normal phenotype
31
Frequency of an X-linked recessive disease in males and females
males: q
females: q^2
32
Hardy-Weinberg equillibrium requires
No mutation occurring at the locus, natural selection is not occuring, completely random mating, no net migration
33
Prader-Willi and Angelman on what chromosome
15
34
Prader-Willi inheritance
Prader lacks Faddah. Maternal imprinting: maternal gene is silent and paternal gene is deleted/mutated
35
AngelMan inheritance
Misses Muddah. Dad gene is normally silent and maternal gene is deleted/mutated.
36
P-W presentation
Hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia
37
Angelman presentation
Inappropriate laughter (happy puppets, seizures, ataxia, and severe intellectual disability)
38
Specific genetics about P-W
25% of cases due to maternal UPD, remaining are mutuation or deletion
39
Specific genetics about Angelman
5% of cases due to paternal UPD, remaining are mutuation or deletion
40
Are P-W and Angelman genes on maternal and paternal side both normally silent????
No...one is usually active. So if you lack the father's chromosome from deletion but the maternal side is not imprinted...will you not have the disease. Or is one or the other imprinted........................
41
Which diseases tend to be worse, aut. rec or aut. dom.
Aut. rec., they tend to pop up in childhood, aut. dom. are often pleiotropic
42
Why aren't x-linked recessive passed male to male
Because the father gives the son the Y chromosome
43
X-linked dom. inheritance
Mothers pass on to 50% of sons AND daughters, fathers transmit to all daughters but no sons
44
Example of x-linked dom. inheritance
Hypophosphatemic rickets
45
Hypophosphatemic rickets
vitamin-D resistant rickets. Increased phosphate wasting and proximal tubule.
46
Mitochondrial myopathies presentation
Myopathy, lactic acidosis, and CNS disease, secondary to failrue in ox phos
47
Muscle biopsy of mitochondrial myopathies
Ragged red fibers
48
Autosomal dominant polycystic kidney disease genetics
85% of cases due to mutation in PKD1 (chromosome 16); remainder due to mutation in PDK2 (chrom. 4)
49
Familial adenomatous polyposis genetics
APC gene, chrom. 5
50
Familial hypercholesterolemia
Defective/absent LDL receptor, can have tendon xanthomas (Achilles!!)
51
Hereditary hemorrhagic telangiectasis
Telangiectasia, recurrent epistaxis, skin discolorations, AVMs, GI bleeding, hematuria.
52
Hereditary spherocytosis genetics
spectrin or ankyrin defects
53
Hereditary spherocytosis CBC w/ diff results
Elevated MCHC
54
Huntington genetics
Chrom 4, trinucleotide repeat disorder (CAG)n.
55
Marfan's genetics
fibrillin-1 gene mutation
56
Marfan syndrome presentation
Tall with long extremities, pectus excavatum, hypermobile joints, and long, tapering fingers and toes (arachnodactyly), cystic medial necrosis of aorta leading to aortic incompetance and dissecting aortic aneurysms, floppy mitral valave. Subluxation of lenses upward and temporally.
57
MEN2 gene
ret gene
58
NF1 (von Recklinghausen disease)
Neurocutaneous: cafe-au-lait spots, cutaneous neurofibromas, aut. dom., 100% penetrance, variable expression. CHROMOSOME 17
59
NF2
Bilateral acoustic schwannomas, juvenile cataracts, meningiomas, and ependymomas. CHROMOSOME 22
60
Tuberous sclerosis
neurocutaneous disorder with numerous benign hamartomas, incomplete penetrance, variable expression
61
von Hippel-Lindau disease
VHL gene (tumor suppressor) on chromosome 3 (3p).
62
Cystic fibrosis genetics
Aut. rec, CFTR gene on chrom. 7, most commonly a deletion of Phe508, most common lethal genetic disease in caucasians
63
Function of CFTR gene
ATP-gated Cl- channel that secretes cl- in lungs and GI tract and reabsorbs Cl- in sweat glands.
64
CF patho
mutations cause misfolded protein that is retained in RER and not transported to cell membrane leading to less Cl- (and H2O) secretion and more Na+ reabsorption to compensate for incrased ICF cl- leading to even less ECF water causing very thick mucus
65
CF membrane potential
Increased Na+ reabsorption causes mroe negative transepithelial potential difference....how....I thought the inside is negative because the na/k atpase pushes an extra cation out, wouldn't this just ruin the membrane potential.
66
CF diagnosis
Cl- conc. >60 mEq/L in sweat is diagnostic, can cause a contraction and hypokalemia (ECF effects like taking a loop diuretic) Renal K+/H+ wasting
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CF CXR
Reticulonodular pattern
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CF genitals
Infertile men (no vas deferens, no sperm)
69
CF PNA
recurrent Pseudomonas
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CF tx
N-acetylcysteine to loosen mucus plugs (cleaves disulfide bonds within mucus glycoproteins). Dornase alfa (DNAse) to clear leukocytic debris
71
X-linked recessive disorders
Be Wise, Fool's GOLD Heeds Silly HOpe.
Bruton agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry disease, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne (and Becker) muscular dystrophy, Hunter Syndrome, Hemophilia A and B, Ornithine transcarbamoylase deficiency
72
CF transepithelial potential difference
More negative because more sodium is being reabsorbed. This is different from membrane potential because I think that actually goes up because of the sodium rushing in, unless the Cl- still makes it more negative.
73
Duchenne mutation
X-linked frameshift
74
Gower manuever
using upper extremities to help kids stand up
75
Duchenne age of onset
Before 5 yrs
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MCC of death in Duchenne's
dilated cardiomyopathy
77
Dystrophin purpose
connects intracellular cytoskeleton (actin) to the transmembrane proteins alpha and beta-dystroglycan, which are connected to the ECM. without in you get myonecrosis
78
Duchenne's bloodwork
Increased CPK and aldolase scene
79
Duchenne's dx
Western blot and muscle biopsy confirm diagnosis
80
Becker mutation
X-linked point mutation
81
Becker onset
Adolescene or early adulthood
82
Myotonic dystrophy type 1 genetics
CTG trinucleotide repeat expansion in the DMPK gene leading to abnormal expression of myotonin protein kinase
83
Myotonic type 1 presentation
Myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy, and arrhythmia
84
Myotonia is
Delayed relaxation with prolonged contraction, muscle may be warmed up to limit the myotonia
85
Fragile X genetics
FMR1 gene on X chrom. affecting the methylation and expression of the FMR1 gene.
86
Fragile X epidemiology
2nd MCC of genetic intellectual disability (after Down's)
87
Fragile X presentation
Post-pubertal macroorchidism (enlarged testes), long face with a large jaw, large everted ears, autism, mitral valve prolapse
88
Fragile X genetic path
Trinucleotide repeat disorder (CGG)
89
Fragile X mnemonic
eXtra large testes, jaw, and ears
90
GAA
Friedreich ataxia
91
CAG
Huntington
92
CTG
Myotonic dystrophy
93
CGG
Fragile X
94
Mnemonic for Trinucleotide repeat disorders
X-Girlfriend's First Aid Helped Ace My Test (the middle letter of each repeat)
95
Down syndrome presentation
MR, flat facies, epicanthal folds, palmar crease, gap between 1st 2 toes, duodenal atresia, Hirschsprung's, congenital heart disease (ostium primum-type ASD), Brushfield spots. Inc. risk of ALL, AML< and Alzheimer's (>35 years old)
96
Down's genetics
1:700. 95% due to nondisjunction. 4% due to reobersonian translocation. 1% due to mosaiciism (post-fertilization mitotic error)
97
Down syndrome First trimester diagnosis
US: Inc. nuchal translucency and hypoplastic nasal bone
Serum: PAPP-A is down, betahCG is up
98
Down syndrome Second trimester diagnosis
Serum: low AFP, high beta-hCG, low estriol, inc. inhibin A
99
Edwards syndrome presentation
Severe MR, rocker-bottom feet, micrognathia, low set Ears, clenched hands, prominent occiput, cong. heart disease, death within 1 yr
100
Edwards syndrome genetics
(E)lection age (18)
| 1:8000, most common trisomy resulting in live birth after Down's
101
Edwards serum
PAPP-A and free betahCG down in first trimester.
| Quad screen: low AFP, low betahCG, low estriol, low or normal inhibin A
102
Patau syndrome presentation
severe MR, rocker bottom feet, microphthalmia, microcephaly, cleft liP/Palate, holoProsencephaly, Polydactyly, congenital heart disease, death within 1 yr
103
Patau genetics
(P)uberty 13
104
Patau serum
First-trimester: low betahCG, low PAPP-A and increased nuchal translucency
105
Draw out a table of the three viable trisomies bloodwork in pregnancy
....
106
Draw out nondisjunction
.....
107
What are acrocentric chromosomes
have centromeres near the ends
108
Robertsonian translocation
Acrocentric chromosomes fuse with loss of both short arms, can be balanced or unbalanced
109
Which chromosomes can undergo robertsonian translocation
paris 13, 14, 15, 21 and 22
110
What happens to the short arms in a robertsonian translocation
The reciprocal product is formed from the long armed chromosome but because they have useless genes they are usually lost quickly.
111
Cri-du-chat syndrome genetics
Congenital microdeletion of short arm of chrom. 5 (46,XX or XY, 5p-)
112
Cri-du-chat presentation
Microcephaly, moderate to severe MR, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities (VSD)
113
Williams syndrome genetics
Congenital microdeletion of long arm of chrom. 7 (deleted region includes elastin gene)
114
Williams presentation
Elfin facies, MR, hypercalcemia (incr. sensitivity to vit. D), well developed verbal skills, extremely friendly, CV problems
115
What are the 22q11 deletion syndromes
DiGeorge and Velocardiofacial syndromes
116
CATCH-22
Cleft palate, abnormal facies, thymic aplasia, cardiac defects, hypocalcemia secondary to parathyroid aplasia, due to microdeletion at chromosome 22q11.
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22q11 deletion path
Aberrant development of 3rd and 4th branchial pouches
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DiGeorge syndrome presentation
thymic, parathyroid, and cardiac defects
119
Velocardiofacial syndrome
palate, facial, and cardiac defects
120
B1
thiamine (TPP)
121
B2
riboflavin (FAD,FMN)
122
B3
niacin: NAD+
123
B5
pantothenic acid (CoA)
124
B6
pyridoxine (PLP)
125
B7
biotin
126
B9
folate
127
B12
cobalamin
128
What B vitamins stored in liver
B12 and folate, the rest are peed out
129
B-complex deficiencies typical presentation
Dermatitis, glossitis, and diarrhea
130
Vitamin A is used as treatment for
Treats measles and AML, subtype M3. Retin-A for wrinkles and acne
131
Vitamin A phys
Antioxidant, visual pigments (retinal), normal differentiatino of epithelial cells into specialized tissue (pancreatic cells, mucus cells), prevents squamous metaplasia
132
Vit A Deficiency
Night blindness (nyctalopia); dry, scaly skin (xerosis cutis); alopecia; corneal degeneration (keratomalacia); immune suppression
133
Vit A Excess
Arthralgias, skin changes (scaly), alopecia, pseudotumor cerebri, cerebral edema, osteoporosis, hepatic abnormalities, teratogenic (cleft palate, cardiac abnormalities), so a negative preg. test and relaiable contraception are needed before isotretinoin is prescribed for severe acne
134
Thiamine function
Thiamine pyrophosphate (TPP): cofactor for several dehydrogenase enzyme reactions: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase (TCA cycle), transketolase (HMP shunt), Branched chain ketoacid dehydrogenase
135
Thiamine mnemonic
ATP: alpha-ketoglutarate dehyd., transketolase, pyruvate dehydroganase ....and throw in branched chain ketoacid dehydrogenase
136
Thiamine deficiency presentation
Wernicke-Korsakoff: triad (confusion, ophthalmoplegia, ataxia); confabulation, personality change, memory loss (permanent).
Ber1Ber1: Dry: polneuritis, symmetrical muscle wasting. Wet: high output cardiac failure (dilated cardiomyopathy), edema.
137
Wernicke-Korsakoff path
Damage to medial dorsal nucleus of the thalamus, mammillary bodies
138
Thiamine deficiency path
Impaired glucose breakdown, ATP depeltion worsened with glucose infusion; highly aerobic tissues (brain, heart) affected first.
139
Thiamine def. cause
Malnutrition and alcoholism
140
Thiamine def. diagnosis
Increased RBC transketolase activity following thiamine administration
141
Thiamine is what B vitamin
B1
142
Riboflavin function
Part of FAD and FMN, used as cofactors in redox reactions, e.g. succinate dehydrogenase reaction in the TCA cycle
143
Riboflavin deficiency
Cheilosis and Corneal vascularization (2 C's of B2)
144
Niacin function
NAD+, NADP+.
145
Niacin tx
dyslipidemia, lowers VLDL and raises HDL
146
Niacin synthesis
Need tryptophan, synthesis requires B2 and B6
147
Niacin deficiency
Glossitis. Severe is pellagra (caused by Hartnup disease and malignant carcinoid syndrome), and isoniazid.
148
Pellagra presentation
3 D's of B3: diarrhea, dementia, dermatitis
149
Dermatitis in pellagra
Casal necklace or hyperpigmentation of sun-exposed limbs
150
Tryptophan metabolism in Hartnup, carcinoid, and isoniazid
Hartnup: dec. trypt absorption
Carcinoid: Inc. trypt metabolism
Isoniazid: decreased B6
151
Niacin excess
Facial flushing (prostaglandin, not histamine), hyperglycemia, hyperuricemia
152
Pantothenate function
Coenzyme A and fatty acid synthase
153
B5 is
"pento"thenate
154
Pantothenate deficiency
Dermatitis, enteritis, alopecia, adrenal insufficiency
155
Pyridoxine function
Converted to pyridoxal phosphate, used in transamination (ALT and AST), decarboxylation reactions, glycogen phosphorylase. Synthesis of cystathionine, heme, niacin, histamine, serotonin, epinephrine, norepinephrine, dopamine, and GABA
156
Pyridoxin deficiency
Convulsions, hyperirritability, peripheral neuropathy (isoniazid and oral contraceptives), sideroblastic anemias due to impaired hemoglobin synthesis and iron excess
157
Biotin Function
Cofactor for carboxylation enzymes (which add 1-carbon group)
158
Biotin mnemonic
Avidin in egg whites avidly binds biotin
159
Biotin reactions
Pyruvate carboxylase
AcetylCoA carboxylase
Propionyl-CoA carboxylase
160
Biotin deficiency
Rare. Dermatitis, alopecia, enteritis. Caused by abx or excessive ingestion of raw egg whties
161
folate function
Turned into tetrahydrofolate for 1-carbon transfer/methylation reactions. Synthesizing nitogenous bases in DNA and RNA
162
Folate sources
Leafy green vegetables, absorbed in jejunum. Folate from Foliage.
163
Folate deficiency
macrocytic, megaloblastic anemia; hypersegmented PMNs, glossitis, no neurologic symptoms
164
folate def. labs
increased homocysteine, normal methylmalonic acid
165
folate def. in US
most common vit. deficiency, seen in alcoholics and pregnancy
166
folate def. causes
Phenytoin, sulfonamides, methotrexate
167
Cobalamin function
cofactor in homocysteine methyltransferase (transfers methyl groups as methylcobalamin) and methlmalonyl-CoA mtuase
168
Cobalamin deficiency
macrocytic, megaloblastic anemia; hypersegmented PMNs, paresthesias, subacute combined degeneration due to abnormal myelin
169
What is subacute combined denegeration
degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts.
170
Cobalamin blood work
elevated serum homocysteine and methylmalonic acid levels
171
Permanent effect of prolonged B12 deficiency
irreversible nerve damage
172
Cause of B12 deficiency
Only made by microorganisms, only from animal products. Veganism, malabsorption (Diphyllobothrium latum), lack of intrinsic factor (pernicious anemia, gastric bypass surgery), or absence of terminal ileum (Crohn's).
173
Diagnosis of pernicious anemia
Anti-intrinsic factor antibodies
174
Draw out reactions for B12 and B6
....
175
What are the B12 reactions
Homocysteine to Methionine via Homocysteine methyltransferase AND methylmanolyl-CoA to succinyl-CoA via methylmalonyl-CoA mtuase
176
What are the B6 reactions
Homocysteine to cysteine and Succinyl-CoA to Heme....but not all of them??
177
Folates (B9) reactions
Used in reaction from homocysteine to methionine but not in forming succinyl-CoA (which is used for myelin synthesis)
178
Vit C functions
helps iron absorption by reducing to Fe2+ state
Hydroxylating proline and lysine in collagen
Needed for dopamine Beta-hydroxylase to convert DA to NE
179
Treatment for methemoglobinemia
Vit C is ancillary tx by reducing Fe3+ to Fe2+
180
Scurvy presentation
swollen gums, bruising, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, corkscrew hair, weakened immune systhem
181
Vit. C excess
N/V/D, fatigue, calcium oxalate kidney stones. Increased risk of iron toxicity for people who receive transfusions, hereditary hemochromatosis
182
D2
ergocalciferol: from plants
183
D3
cholecalciferol: milk, sun-exposed skin (stratum basale)
184
Vit D storage form
25-OHD3
185
Vit D active form
1,25-(OH)2D3 (calcitriol)
186
Vit D function
Inc. intestinal absorption of calcium and phosphate, inc. bone mineralization
187
Vit D def.
Rickets in kids, osteomalacia in adults, hypocalcemic tetany
188
Breastmilk and Vit D
Low in Vit D, breastfed babies need oral vitamin D
189
Vit D Excess
HyperCa, hypercalciuria, loss of appetite, stupor
190
Causes of Vit D excess
Sarcoid (inc. activation of vitamin D by epitheliod macrophages)
191
Vit E is also called
tocopherol and tocotrienol
192
Vit E function
Antioxidant (protects RBCs and membranes from free radical damage)
193
Vit E and blood thinners
Can enhance anticoagulation due to warfarin
194
Vit E Def.
hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demyelination
195
Vit E def. simply explained
Like B12, with no anemia, PMN changes, or increased serum methylmalonic acid levels
196
Vit K function
Cofactor for gamma-carboxylation of glutamate residues on proteins for blood clotting (II, VII, IX, X) and proteins C and S
197
Vit K def. presentation
Inc. PT and aPTT with normal bleeding time
198
Vit K def. causes
Neonates (no bacteria in gut), prolonged use of broad-spectrum antibiotics
199
Vit K and breast milk
Not in breast milk, neonates need an injection at birth
200
Zinc function
```
Essential for the activity of 100% enzymes.
Zinc fingers (transcription factor motifs)
```
201
Zinc def.
Delayed wound healing, hypogonadism, less adult hair, dysgeusia, anosmia, acrodermatitis enteropathica, may predispose to alcoholic cirrhosis
202
What reactions happen in the mitochondria
Beta-oxidation, acetyl-CoA production, TCA cycle, Ox phos
203
What reactions happen in the cytoplasm
Glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER), cholesterol synthesis
204
What happens in both mitochondria and cytosol
Heme synthesis, Urea cycle, Gluconeogenesis (HUGs take two)
205
What is a phosphorylase
Adds phosphate without ATP (e.g. glycogen phosphorylase)
206
What is a carboxylase
Transfers CO2 groups with the help of biotin (e.g. pyruvate carboxylase)
207
Mutase does
relocates a functional group within a molecule
208
Know what type of enzyme specific ones are??
????
209
What cofactor is needed for ethanol metabolism
NAD+ (turned into NADH)
210
limiting reagent in ethanol metabolism
NAD+
211
Kinetics of alcohol metabolism
zero-order kinetics
212
NADH/NAD+ ratio in alcohol metabolism
Increases in liver
213
What is the effect of the NADH/NAD+ ratio on pyruvate, oxaloacetate, and glyceraldehyde-3-phosphate
Lactate, malate and glycerol-3-phosphate
214
Fomepizole
Inhibits alcohol dehydrogenase (used to treat methanol or ethylene glycol poisoning)
215
Disulfiram
Inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover sxs)
216
Elevated NADH/NAD+ prevents TCA production of NADH causing increased utilization of acetyl-CoA for ketogenesis (ketoacidosis) and lipogenesis (hepatosteatosis)
....
217
Kwashiorkor....
.....
