RAPID REVIEW

Question 1

What is the mechanism behind Lesch-Nyhan syndrome?

Answer 1

Absent HGPRT → ↓ de novo purine synthesis → ↑ uric acid production

Question 2

What causes β-thalassemia?

Answer 2

Mutation at splice site or promoter sequences → retained intron in mRNA

Question 3

What is the mechanism of Lynch syndrome?

Answer 3

Failure of mismatch repair during the S phase → microsatellite instability

Question 4

What is the enzyme defect in I-cell disease?

Answer 4

N-acetylglucosaminyl-1-phosphotransferase defect → Golgi fails to phosphorylate mannose residues → lysosomal enzymes not targeted properly

Question 5

What causes osteogenesis imperfecta?

Answer 5

Type I collagen defect due to COL1A1 or COL1A2 gene mutations

Question 6

What is the molecular defect in Marfan syndrome?

Answer 6

FBN1 mutation on chromosome 15 → defective fibrillin

Question 7

What causes cystic fibrosis?

Answer 7

Autosomal recessive ΔF508 mutation in CFTR gene → misfolded protein → defective ATP-gated Cl⁻ channels

Question 8

What is the trinucleotide repeat disorder in Myotonic dystrophy?

Answer 8

CTG repeat expansion in DMPK gene → abnormal expression of myotonin protein kinase

Question 9

What is the metabolic issue in Wernicke encephalopathy?

Answer 9

Thiamine deficiency → impaired glucose breakdown → ATP depletion worsened by glucose infusion

Question 10

What causes hereditary fructose intolerance?

Answer 10

Aldolase B deficiency → Fructose-1-phosphate accumulation → ↓ available phosphate → inhibition of glycogenolysis and gluconeogenesis

Question 12

What causes hereditary angioedema?

Answer 12

C1 esterase inhibitor deficiency → unregulated activation of kallikrein → ↑ bradykinin

Question 13

What is the immune defect in DiGeorge syndrome?

Answer 13

22q11 microdeletion → failure to develop 3rd and 4th pharyngeal pouches

Question 14

What is the defect in Hyper-IgM syndrome?

Answer 14

Defective CD40L on Th cells → class switching defect

Question 15

What causes Chronic granulomatous disease?

Answer 15

NADPH oxidase defect → ↓ ROS → impaired respiratory burst in neutrophils

Question 16

What is the pathophysiology of Graft-versus-host disease?

Answer 16

Type IV hypersensitivity reaction; donor T cells attack host cells

Question 17

What is the bacterial toxin mechanism in botulism?

Answer 17

Toxin cleaves SNARE → ↓ acetylcholine release at NMJ

Question 18

What is the mechanism of toxic shock syndrome and scarlet fever?

Answer 18

TSST-1 and erythrogenic exotoxin A cross-link β region of TCR to MHC II → massive cytokine release (IL-1, IL-2, IFN-γ, TNF-α)

Question 19

What causes sudden death in hypertrophic obstructive cardiomyopathy (HOCM)?

Answer 19

Sarcomeric protein gene mutations (e.g., myosin-binding protein C) → asymmetric septal hypertrophy → outflow obstruction

Question 20

What causes hypovolemic shock?

Answer 20

↓ preload → ↓ cardiac output

Question 21

What is the most common cause of congenital adrenal hyperplasia?

Answer 21

21-hydroxylase deficiency → ↓ mineralocorticoids and cortisol → ↑ ACTH → adrenal hyperplasia

Question 22

What causes nephrogenic diabetes insipidus?

Answer 22

ADH resistance → inability to concentrate urine

Question 23

What is the mechanism of diabetic ketoacidosis?

Answer 23

↓ insulin or ↑ insulin requirement → fat breakdown → ↑ free fatty acids → ketogenesis

Question 24

What is the pathophysiology of duodenal atresia?

Answer 24

Failure to recanalize

Question 25

What causes superior mesenteric artery (SMA) syndrome?

Answer 25

Diminished mesenteric fat → compression of transverse duodenum between SMA and aorta

Question 26

What is the cause of achalasia?

Answer 26

Loss of postganglionic inhibitory neurons (NO and VIP) in myenteric plexus → failure of LES relaxation

Question 27

uniparental disomy or imprinting leading to silencing of maternal gene. Disease expressed when paternal allele deleted or mutated

Answer 27

Prader Willi Syndrome

Question 28

defective ATP7A protein --> impaired copper absorption and transport --> decreased lysyl oxidase activity --> decreased collagen cross linking

Answer 28

MENKES Disease

Question 29

silenced paternal gene leading to mutation, lack of expression, or deletion of UBE3A on maternal chromosome 15

Answer 29

Angelman Syndrome

Question 30

CGG trinculeotide repeat on FMR1 gene --> hypermethylation --> decreased expression

Answer 30

fragile X syndrome

Question 31

decreased differentiation of epithelial cells into specialized tissue --> squamous metaplasia

Answer 31

Bitot spots in vitamin A deficiency

Question 32

tryptophan is diverted towards serotonin synthesis by tumor --> B3 deficiency

Answer 32

pellagra in malignant carcinoid syndrome

Question 33

protein malnutrition --> decreased oncotic pressure leading to edema --> decreased apoliprotein synthesis

Answer 33

Kwashiorkor

Question 34

INcreased NADH/NAD+ ratio due to ethanol metabolism

Answer 34

lactic acidosis, fasting hypoglycemia, gepatic steatosis in alcoholism

Question 35

increased permability of mitochondrial membrane --> decreased proton (H+) gradient and increased O2 consumption --> uncoupling

Answer 35

Aspirin induced hyperthermia

Question 36

burning feet syndrome, dermatitis, enteritis, alopecia

Answer 36

pentothenic acid (b5 deficiency)

Question 37

megaloblastic anemia, subacute combined degeneration, paresthesias, cognitive changes

Answer 37

Cobalmin (B12) deficiency; malabsorption, decreased intrinsic factor, absent terminal ileum

Question 38

swollen gums, mucosal bleeding, poor wound healing, petechiae, corkscrew hairs, perifollicular hemorrhages

Answer 38

scurvy (vit c deficiency)

Question 39

intellectual disability, musty body odor, hypopigmented skin, eczema

Answer 39

phenylketonuria

Question 40

bluish black connective tissue, ear cartilage, sclera severe arthralgias, urine turns black on prolonged exposure to air

Answer 40

alkaptonuria

Question 41

wilms tumor, macroglossia, organomegaly, hemihyperplasia, omphalocele

Answer 41

Beckwith Wiedemann syndrome WT2 mutation