Diseases of biochem pathways pg 105-118

Question 1

What is the deficiency in chronic granulomatous disease?

Answer 1

NADPH oxidase can’t oxidize O2 to make superoxide to make radicals to kill phagocytosed bacteria. Patients are at risk to catalase positive species (S auerus and aspergillus)

Question 2

What is the problem in G6PD? What are heinz bodies? Sorry, the answer will be lengthy, but maybe it will be helpful.

Answer 2

Can’t reduce NADP, so low NADPH and can’t reduce GSSG which would otherwise be 2 GSH which glutathione peroxidase would use to reduce H2O2 to make 2H2O, which would save RBCs.

RBCs will get oxidative damage and hemolytic anemia.

Heinz bodies are oxidized Hemoglobin, Bite Cells are from phagocytic removal of Heinz bodies in spleen. (Think Bite into Heinz ketchup covering your fava beans or sulfonamides, or anti-tb/malaria drugs, whatever you like ketchup on)

Question 3

What is going on in essential fructosuria? Is it bad?

Answer 3

Benign autosomal recessive. Deficiency in fructokinase, so you can’t phosphorylate fructose to be metabolized.

Results in fructose in blood and urine, but fructose is not trapped in cells so no real symptoms.

Question 4

What is going on in fructose intolerance? is it bad/

Answer 4

Potentially bad autosomal recessive deficiency of aldolase B. It is bad b/c it is downstream of phosphorylation of fructose, and it creates a phosphate sink.

Must reduce intake of sucrose and fructose otherwise it is bad!

Question 5

Is galactokinase deficiency bad?

Answer 5

can cause infantile cataracts, and failure to develop a social smile.

Galactocitol can be accumulated in cells if it is present in the diet. So reduce intake.

Question 6

What is galactosemia?

Answer 6

BAD! Galactose 1 phosphate uridyltransferase deficiency. It is analogous to fructose intolerance b/c it is downstream of phosphorylation of galactose and results in phosphate sync and creates accumulation of toxic galactitol in cells.

FAB GUT. Fructoseis to Aldolase B as Galactose is to UridylTransferase

Question 7

Why does hyperglycemia screw with vision?

Answer 7

Sorbitol pathway. Lens has aldose reductase to make glucose into sorbitol, which then causes a gradient to make the lens absorb water. Then there is a gradient for glucose to come in to make more sorbitol to make more water come in and make the lens swell more.

Question 8

What is the most common urea cycle disorder (think genetics)?

What do you see with it in labs and on presentation?

Answer 8

Ornithine transcarbamylase deficiency (it is X linked, instead of autosomal recessive so it is statistically more likely since you don’t need 2 bad genes)

Cant bring carbamoyl phosphate to join ornithine in the urea cycle, so NH3 builds up which causes tremor, slurring of speech, vomitting, cerebral edema. Often presents early in fetal life.

High orotic acid b/c excess carbamoyl phosphate is turned into orotic acid. Low BUN b/c urea is not being produced.

Question 9

What do the beta agonists synthesized from?

Answer 9

Phenylalanine to tyrosine to dopa to DOPAMINE to NE to EPI

Question 10

How do you treat phenylketonuria?

Answer 10

Musty smelling babies need decreased phenylalanine and increased tyrosine in diet. Otherwise growth and mental retardation, seizures, fair skin, eczema, musty odor

Question 11

How does alkaptonuria present?

Answer 11

Urine turns black after exposure to air is Dx. Patients will have darkening connective tissue, and debilitating arthritis as they get older

Question 12

What do you see in homocystinuria? How do you treat it?

Answer 12

Profound late onset of intellectual defects.
MARFANS SIMILAR: Tall stature, subluxtion of lens (but downward and in instead of up like mar fans), atherosclerosis

And duh, HIGH homocysteine in urine.

Treatment is by giving more of the dietary amino acid that cannot be made, either methionine or cystein depending on the enzyme deficiency (because homocysteine can be metabolized by either homocysteine methyltransferase or cystathionine synthase. The deficiencies in one or the other cause homocysteinuria)

Question 13

What causes maple syrup urine disease?

Answer 13

Automal recessive can’t degrade branched amino acids b/c alpha ketoacid dehydrogenase sucks.

I Love Vermont MAPLE SYRUP from tree BRANCHES. (Isoleucine, leucine, valine are BCAA)

Question 14

How do you remember which glycogen storage disease is 1, 2, 3, 5?

Answer 14

Very Poor Carbohydrate Metabolism
Von Gierke
Pompe
Cori
McArdle

Question 15

What is going on in Von Gierke Disease? Findings? Tx?

Answer 15

Type 1: Glucose-6-phosphatase. MAKES SENSE that it would be one.

Findings: SEVERE fasting hypoglycemia (no last step of gluconeogenesis to allow glucose into blood), lots of glycogen in liver, high lactate. Hepatomegaly. Glucose stuck in liver

Tx: frequent sugar intake, avoid fructose/galactose

Question 16

What is going on in pomp disease? Finding? Tx?

Answer 16

Type II GSD. Lysoosmal alpha 1,4 glucosidase is important in heart.

Cardiomyopahy leading to death (Pompe trashes Pump, heart, liver, muscle)

Question 17

What is going on in cori disease? Findings? Tx?

Answer 17

Type III GSD: Debranching enzyme is bad and more mild than most types b/c cans still get glucose out until it gets to the branching point.

Kid has enlarged liver, not much in adults. Normal blood lactate. Fasting hypoglycemia, but not as profound as type 1 b/c some available glucose, and gluconeogenesis is in tact.

Question 18

What is going on in McArdle disease? Findings? Tx?

Answer 18

Skeletal muscle glycogen phosphorylase (breaks down glycogen makes sense b/c glucose 6 phosphate is knocked off of glycogen [glycogen synthase makes glycogen])

Myoglobinuria and muslce pain with exercise b/c can’t break down muscular glycogen.

McArdle is Muscle (both start with M)

Tx: avoid exercise, sorry.

Question 19

Fabry disease cause? Presentation? Accumulated substrate?

Answer 19

X recessive lysosomal storage disease. Peripheral neruopathy, CV/renal disease. Ceramide trihexoside accumulates b/c galacosidase A doesn’t work

Question 20

Gaucher disease cause? Presentation? Tx? Accumulated substrate?

Answer 20

lysosomal storage disease

Gaucher is hepatosplenomegaly, pancytopenia, bone crisis

Caused by Glucocerbrosidase so you have build up of glucocerebroside (starts with G)

GAUCHER CELLS are cells looking like crumpled tissue paper.

Tx: recombinant glucocerebrosidase

Question 21

Niemann-Pick disease cause? Presentation? Accumulated substrate?

Answer 21

lysosomal storage disease

NO MAN PICKS (niemann-pick) his nose with his SPHINGer (sphingomyelinase deficiency)

Progressive neurodegeneration Cherry red spot (like tay sacks), foam cells b/c lipid laden macrophage, hepatosplenomegaly (unlike tay sachs)

Sphingomyelin accumulates, makes sense with sphingomyelinase deficiency

Question 22

Tay-Sachs cause? Presentation? Accumulated substrate?

Answer 22

lysosomal storage disease

tay-saX is heXosaminidase deficiency: so GM2 ganglioside accumulation.

Progressive neurodegen, cherry red on macula (like nieman picks), lysosomes are onion skin

Question 23

Krabbe disease cause? Presentation? accumulated substrate?

Answer 23

lysosomal storage disease

Galactocerbrosidase problem (Mr. Krabbe’s Krabby patties are out of this GALAxy).

Perifpheral neuropathy, optic atrophy, globoid cells

Galactocerbrosidem pyschosine accumulateion.

Question 24

What causes metachromatic leukodystrophy?

Answer 24

lysosomal storage disease

Arylsulfatase A causes cerebroside sulfate accumulations.

Ataxia and demylelination both central and peripheral

Question 25

What is the cause of hurler syndrome? Presentation? Acumulation?

Answer 25

lysosomal storage disease

Alpha L iduronidase deficient.

Developmental delay, gargoylism, airway obstruction, corneal clouding and hepatosplenomegaly.

Heparan sulfate accumulates

THINK MARK STICE HURLS the discuss (and booze), and he is agargoyl who snores with airway obstruction and is obviously developmentally delated.

Question 26

How is hunter syndrome similar to hurler syndrome? What is the difference?

Answer 26

Hunter syndrome is same accumulation of substrate(heparan sulfate and derma tan sulfate) but different enzyme (iduronate sulfates).

Hunters see clearly (no corneal clouding) and AGGRESSIVELY aim for X (X linked)

It is similar presentation except add aggressive behavior as shown above and X linked

Question 27

What happens with carnitine deficiency?

Answer 27

LCFAs can’t go into mitochondria, so toxic accumulation and weakness and hypotonia and hypoketotic hypoglycemia.

CARNitine normally causes CARNage of fatty acids