Inborn Errors of Metabolism

Question 1

Cannot convert galactose to glucose efficiently, most common carbohydrate defect, Galactose-1-phosphate uridyl transferase defect

Answer 1

galactosemia

Question 2

why is galactosemia bad?

Answer 2

conversion to galcitol and galactonate (cataracts, failure to thrive in infants)
- dietary component is now a mild toxin (Galactose is part of lactose, milk sugar)

Question 3

Defect in fructose 1,6 bispohosphate aldolase

Answer 3

Hereditary Fructose Intolerance

Question 4

What can be an indicator of Hereditary Fructose Intolerance in a child’s actions?

Answer 4

Does not like CANDY, or fruit (they learn what foods make them feel bad)

Question 5

Von Gierke Disease

Answer 5

Glycogen storage disorder, Defect in glucose-6-phosphatase, build up of glycogen, can’t maintain blood sugar (hypoglycemia) and hepatomegaly occur

Question 6

considered an essential amino acid due to its ability to produce tyrosine

Answer 6

Phenylalanine

Question 7

defect in Phenylalanine hydroxylase gene (PAH)

Answer 7

PKU (phenylketonuria)

Question 8

name some symptoms of PKU

Answer 8

paler skin and eyes, retardation,

Question 9

How to treat PKU

Answer 9

give the pt tyrosine and keep phenylalanine levels low since tyrosine and phenylalanine compete for the same receptors

Question 10

Cannot metabolize branched chain ketoacids from branched chain amino acids

Answer 10

Maple Syrup Urine Disease (MSU)

Question 11

Rare except in Menonites of Lancaster County

1 in 7 is a carrier there, same mutation

Answer 11

MSU

Question 12

how MSU produces its effects

Answer 12

Accumulation of BCAA and byproducts can lead to neurodegeneration and death in months (BCAAs compose 40% of protein, HUGE part of your diet)

Question 13

Most common fatty acid metabolism defect

Answer 13

MCAD Deficiency (Medium-chain acyl-coenzyme A dehydrogenase)

Question 14

marked with hypoglycemia after fasting, insufficient ketone bodies, glycogen gone, vomiting and lethargy after minor illness

Answer 14

MCAD

Question 15

MCAD treatment

Answer 15

supportive care to restore glucose stores (avoid fasting and get them calories from glucose)

Question 16

Block in corticosteroid synthesis

Lipid defect of cholesterol metabolism and steroid synthesis

Answer 16

Congenital Adrenal Hyperplasia

Question 17

Most severe peroxisome biogenesis disorder, why?

Answer 17

Zellwegger Syndrome, can’t make peroxisomes (completely absent) and unlikely to allow you to survive, missing a whole section of metabolism

Question 18

only X linked Mucopolysaccharidoses

Answer 18

Hunter’s Disease (X-linked)

Question 19

Hurler and Scheie are mutations in α-L-iduronidase, which is more severe

Answer 19

Hurler

Question 20

ß-glucosidase deficiency

Rare, except Ashkenazi Jews, and is a type of __________

Answer 20

Gaucher, Sphingolipodoses

Question 21

ß-hexosaminidase A deficiency

Answer 21

Tay Sachs

Question 22

sphingomyelinase deficiency

Answer 22

Nieman Pick

Question 23

I-cell Disease Deficiency, what does it cause, and how does it present

Answer 23

No Mannose-6-phosphate on the enzymes due to lack of phosphotransferase
You accumulate what the lysosomes are supposed to be degradeed

Question 24

4 enzymes that if deficient lead to build of ammonia (urea cycle disorder)

Answer 24

Carbamoyl phosphate synthetase (CPS)
Ornithine transcarbamoylase (OTC)
Argininosuccinate synthetase (ASA)
Argininosuccinase (AS)

Question 25

why can female carriers for OTC deficiency be symptomatic

Answer 25

X mosaicism, will either have the good or defected OTC gene active

Question 26

How cystinuria causes problems

Answer 26

defect in transporter, can’t reuptake from glomerular filtrate, goes the kidneys, accumulates and crystallizes possbily causing kidney stones

Question 27

ways to treat cytinuria

Answer 27

try to make it more soluble, raise acidity of urine, make urine more dilute

Question 28

transporter out of lysosmes is defective (intracellular kindey stones)

Answer 28

Cystinosis

Question 29

Wilson’s Disease

Answer 29

Defect in copper excretion to biliary tract

leads to liver disease

Question 30

Kayser-Fleischer ring in the eye

Answer 30

Wilson’s Disease

Question 31

Hereditary Hemochromatosis

Answer 31

Excessive iron absorption in intestine
Accumulates in liver, kidney, heart, joints, pancreas
Very common in Northern Europeans, 1 in 8 is carrier

Question 32

How to diagnose Hemochromatosis

Answer 32

liver biopsy with hemosiderin staining

Question 33

How can 1 in 8 be carriers in hemochromatosis

Answer 33

Carriers and people that are effected are more efficient at taking up iron, taking it up in the diet means they will actually be healthier and will therefore be passing on the gene and reproducing

Question 34

Class I-like gene called HFE
Binds transferrin receptor on cell surface
Inhibits iron uptake (intestine and brush border)

Answer 34

Hemochromatosis Genetics I

Question 35

deficiency in phosphotransferase

Answer 35

I-Cell Disease

Question 36

Genes for cystinuria types 1, 2, and 3

Answer 36

SLC3A1, SLC7A9

Question 37

MCAD genetic mutation

Answer 37

Missense A-G, glutamate for lysine

Question 38

CAH genetic mutation

Answer 38

CYP21A2 codes for 21-hydroxylase

Question 39

alpa-L-iduronidase mutation

Answer 39

Mucopolsachrodoses

Question 40

Genetic mutation in wilson disease

Answer 40

ATP7B

Question 41

c282Y mutation causing switch from cysteine to tyrosine

Answer 41

Hemochromatoses