Biochemistry and Genetics

Question 1

Familial chylomicronemia syndrome (Type I) AR

• Protein defect
• Elevated lipoproteins
• Symptoms

Answer 1

• LPL and APOC-II
• Chylomicrons
• Acute pancreatitis, lipemia retinals, eruptive xanthomas, hepatosplenomegaly

Question 2

Familial hypercholesterolemia (Type IIA) AD

• Protein defect
• Elevated lipoproteins
• Symptoms

Answer 2

• LDL receptor, APOB-100
• LDL
• Premature CAD, corneal Marcus, tendon anthems, xanthelasmas

Question 3

Familial dysbetalipoproteinemia (Type III)

• Protein defect
• Elevated lipoproteins
• Symptoms

Answer 3

• APOE
• Chylomicron and VLDL remnants
• Premature CAD and PVD
• Tuboeruptive palmar xanthomas

Question 4

Familial hypertriglyceridemia (Type IV) AD

• Protein defect
• Elevated lipoproteins
• Symptoms

Answer 4

• APOA-V
• VLDL
• Pancreatitis, obesity and insulin resistance association

Question 5

APO: mediates remnant uptake

Answer 5

APO-E

Question 6

APO: Activates LCAT

catalyzes esterification of cholesterol, matures HDL

Answer 6

APOA-I

Question 7

aPO: LPL cofactor

Answer 7

APOC-II

Found on Chylomicrons and VLDL

Question 8

APO: mediates chylomicron secretion

Answer 8

APOB-48

Question 9

APO: binds LDL receptor

Answer 9

APOB-100

Question 10

Syndrome:
Colorectal cancer, endometrial cancer, and ovarian cancer
-Name the genes and inheritance

Answer 10

Lynch syndrome

• MSH2, MLH2, MSH6, PMS2
• AD
• Inactivated mutation in tumor suppressor gene
• 2 hit loss of suppression

Question 11

Syndrome:
Colorectal cancer, desmoids and osteomas, brain tumors
-Gene and inheritance

Answer 11

FAP

• APC
• AD, 2 hit loss of suppression

Question 12

Syndrome:

Hemangioblastomas, clear cell RCC, pheochromocytoma

Answer 12

VHL

• AD, 2 hit loss of suppression
• c3

Question 13

Syndrome:

Sarcomas, breast ca, brain tumors, adrenocortical carcinoma, leukemia

Answer 13

Li-Fraumeni syndrome

• TP53
• AD, 2-hit loss of suppression
• AKA SBLA disease (sarcoma, breast, leukemia, adrenocortical)

Question 14

Syndrome

-Pituitary, parathyroid, and pancreatic adenomas

Answer 14

MEN1

-AD, 2-hit loss of suppression

Question 15

Syndrome

Medullary thyroid ca, pheochromocytoma, +/- parathyroid hyperplasia

Answer 15

MEN2A/B

• RET oncogene
• AD, gain of function, increases tumor growth

Question 16

Syndrome

• Unilateral cafe-au-alit spots, polyostotic fibrous dysplasia, precocious puberty, multiple endocrine abnormalities
• Name the defect and biochem

Answer 16

McCune Albright Syndrome

• G protein signaling defect
• Mosaicism

Question 17

Hypophosphatemic rickets

• Whats the problem?
• Inheritance
• Presentation

Answer 17

The PCT is dumping too much phosphate

• XD
• Looks like rickets, presents in childhood, will affect all of a father’s daughters but none of his sons

Question 18

MELAS syndrome

Answer 18

mitochondrial encephalopathy, lactic acidosis, and CNS disease
Failure in ox phase
“Ragged red fibers”
All offspring of affected femalee will have some degree of disease

Question 19

Branching skin lesions, recurrent nose bleeds, skin discolorations, AVMs, GI bleeds, hematuria

Answer 19

Osler-Weber-Rendu syndrome (Hereditary hemorrhagic telangiectasia)
AD

Question 20

Cafe au last spots, cutaneous neurofibromas, gliomas, pheochromocytoma, lisch nodules
100% penetrance

Answer 20

NF1

AD, c17

Question 21

bilateral acoustic schwannomas, juvenile cataracts, meningiomas, ependymomas

Answer 21

NF2

AD, c22

Question 22

Hamartomas in the brain, heart, and skin

Variable expression

Answer 22

Tuberous sclerosis

AD

Question 23

Name the relevant AR disease

Answer 23

Autosomal Recessive (PKD) Albinoes Can Frequently Give Haunting Horror Stories That Will Make Phoenixes Kry

ARPKD, Albinism, CF, Glycogen storage dz, hemochromatosis, Hbs, Sphingolipidoses (not hunter), thalassemia, Wilson, mucopolysaccaridoses (not Fabry), phenylketonuria, Kartagener

Question 24

XR disorders

Answer 24

Oblivious female will often give her boys her x-Linked Disorders
Ornithine transcarbamoylase deficiency, Fabry’s, Wiskott-Aldrich, Ocular albinism, G6PD deficiency, Hunter syndrome, Bruton, Hemophilia A and B, Lesch-Nyan syndrome, Duchenne MD

Question 25

Quad screen for Down syndrome (AFP, hCG, Estriol, Inhibin A) RECALL: PAPP-A is low in all three trisomies!!!

Answer 25

AFP low hCG high Estriol low Inhibit A high

Question 26

Quad screen for Edwards syndrome

Answer 26

Edwards=EVERYTHING is low | Edwards "clenched hands"

Question 27

Quad screen for Patau syndrome

Answer 27

p is for palate, liP, holoPro, Polydactyly | Low hCG

Question 28

Cardiac anomaly with cry-du-chat

Answer 28

VSD | 5p microdeletion

Question 29

Williams syndrome metabolic abnormalities

Answer 29

hypercalcemia | 7q deletion, elastin gene down-->elf face

Question 30

RLE of glycolysis

Answer 30

PFK-1 AMP, F-2,6-BP + ATP, citrate --

Question 31

RLE of gluconeogenesis

Answer 31

F-1,6-bisphosphatase AMP, F-2,6,BP --

Question 32

RLE of TCA cycle

Answer 32

isocitrate dehydrogenase ADP+ ATP, NADH-

Question 33

RLE of glycogenesis

Answer 33

Glycogen synthase G-6-P, insulin, cortisol + Epinephrine, glucagon --

Question 34

RLE of glycogenolysis

Answer 34

Glycogen phosphorylase Epinephrine, glucagon, AMP ++ G-6-P, insulin, ATP --

Question 35

RLE of HMP shunt

Answer 35

G6PD NADP ++ NADPH --

Question 36

RLE of De nove pyrmidine synthesis

Answer 36

Carbamoyl phosphate synthetase II ATP, PRPP ++ UTP --

Question 37

RLE of De novo purine synthesis

Answer 37

glutamine-PRPP amidotransferase AMP, IMP, GMP --

Question 38

Urea cycle

Answer 38

Carbamoyl phosphate synthetase I N-acetylglutamate ++

Question 39

RLE of FA synth

Answer 39

Acetyl-CoA carboxylase (ACC) Insulin, citrate ++ Glucagon, palmitoyl CoA --

Question 40

RLE of FA oxidation

Answer 40

Carnitine acyltransferase I Malonyl CoA --

Question 41

RLE of ketogenesis

Answer 41

HMG-CoA synthase

Question 42

RLE of cholesterol synthesis

Answer 42

HMG-CoA reductase Insulin, thyroxine ++ glucagon, cholesterol --

Question 43

``` Severe fasting hypoglycemia Ketosis Hyperlipidemia Lactic acidosis Enlarged liver and kidneys ```

Answer 43

Von Gierke's (AR) Deficient glucose 6 phosphatase in liver and kidney -->Enlarged liver and kidney due to accumulation of normal glycogen (G6P stimulates glycogen synthase b)

Question 44

Infant form: MR, hypotonia, cardiomegaly, death by age 2 | Adult form: gradual skeletal myopathy

Answer 44

Pompe's disease (AR) Deficient alpha-1,4-glucosidase (acid maltase in lysosomes) -->accumulation of normal glycogen in lysosomes -->tissues that depend on lysosomal degradation of glycogen get messed up (the brain, heart, and muscles)

Question 45

Mild hypoglycemia Hepatomegaly Low free glucose after epinephrine challenge LM shows many short branched glycogen chains in the muscle and liver

Answer 45

Cori's disease (AR) Deficient debranching enzyme -->buildup of abnormal glycogen (limit dextrin) -->epinephrine should stimulate glycogenolysis in mm and liver

Question 46

Hepatosplenomegaly Cirrhosis Liver failure and death by age 2 Bx shows very long chains of glycogen with few branches

Answer 46

Andersen's (AR) Deficient in branching enzyme (glucose 4,6 transferase) -->buildup of abnormally long collagen chains in the liver and spleen -->inefficient, buildup and breakdown takes too long -->buildup of G6P-->toxic to liver and spleen

Question 47

Muscle cramping, fatigue, myoglobinuria with strenuous exercise No lactic acidosis after exercise

Answer 47

McArdles (AR) Deficient muscle glycogen phosphorylase -->Muscles can't breakdown the glycogen, quickly run low on glucose after exercise -->Muscle fatigue due to low glucose, not buildup of lactic acid -->Can't even make lactic acid because of how little glucose there is!

Question 48

Early childhood During fasting or metabolic stress, pt presents with lethargy and seizures Pt has hepatomegaly and acute liver injury Cannot breakdown medium-length fatty acids by beta oxidation

Answer 48

MCAD deficient (AR)

Question 49

Impaired used of long-chain fatty acids - mm aches, fatigue after exercise, elevated free FAs in blood, reduced ketone production during fasting - hypoglycemia

Answer 49

Carnitine/carnitine acyltransferase deficiency

Question 50

adrenocortical insufficiency, mental deterioration, spastic paralysis

Answer 50

adrenolebukodystrophy | defective per oxidation of FAs

Question 51

Acetoacetate is a

Answer 51

ketone

Question 52

RLE of ketone synthesis | location

Answer 52

HMG coa synthase | liver mitochondrial matrix

Question 53

three conditions with elevated ketones

Answer 53

DKA pregnancy starvation

Question 54

why can't the liver use ketones for fuel?

Answer 54

it lacks succinyl col:acetoacetate col transferase | can't make acetyl col from ketones

Question 55

acetyl coa x3-->?

Answer 55

HMG coA

Question 56

HMG coa-->mevalonate by what

Answer 56

HMG coa reductase

Question 57

List the plasma lipoproteins in order of increasing density | Which one is the biggest?

Answer 57

chylomicron, VLDL, LDL, HDL | chylomicron