Lecture 35+36

Question 1

Hurler syndrome

Answer 1

deficiency in Iduronidase
accumulation of dermatan sulfate and heparan sulfate
urine will be + for glycosaminoglycans

enzyme replacement therapy can be done

symptoms/signs: 
coarser facial features 
short 
developmental delay 
hepatomegaly and splenomegaly 
reduced joint motility 
corneal clouding

Question 2

Hunter syndrome

Answer 2

milder form of hurler syndrome
X linked recessive (mainly males)

deficient in iduronate sulfatase

symptoms: 
coarser facial features 
hepatosplenomegaly 
mild developmental delay 
NO corneal clouding 

enzyme replacement therapy

Question 3

Tay-sachs disease

Answer 3

deficiency in beta-hexosaminidase A

accumulation of GM2

seen to have: 
progressive neurodegeneration
blindness (cherry red spot on macula) 
developmental delay 
usually fatal between 2-6 years

Question 4

Gaucher disease

Answer 4

most common lysosomal storage disorder

deficient in Beta-glucosidase

accumulation of glucosyl ceramide or glucocerebroside

symptoms:
no neurological damage
hepatosplenomegaly
osteoporosis of long bones (bone crisis)

can use enzyme replacement therapy

Question 5

Fabry disease

Answer 5

X-linked recessive disorder (mainly males are affected)

deficiency in alpha-galactosidase

accumulation of globoside (ceramide trihexoside)

symptoms:
peripheral neuropathy
accumulation of globoside in blood vessels, skin, kidney, nerves, heart

Question 6

Niemann-Pick disease

Answer 6

deficiency in Sphingomyelinase
accumulation of sphingomyelin in neuronal tissues (foamy cell appearance)

Type A:
severe infantile form
fatal by 2-3 years
cherry-red spot on macula (blindness)

Type B:
appears later in childhood
will have hepatosplenomegaly

Question 7

Metachromatic leukodystrophy

Answer 7

deficient in aryl sulfatase A
accumulation of sulfatide

progressive paralysis and demyelination

Question 8

Pompe disease

Answer 8

Generalized accumulation of glycogen in heart, muscle, kidney and liver as vacuoles in the lysosomes

glycogen storage disorder (II)

Question 9

I-Cell disease

Answer 9

defect in trafficking enzymes to the lysosomes
the golgi fails to add the mannose-6 marker, thus they do not go to the lysosome
will be secreted into the blood

will have inclusion cells

symptoms similar to Hurler syndrome, but more severe and earlier age of onset

Question 10

Migalastat

Answer 10

drug treatment for Fabry- pharmaceutical

chaperone which helps the mutated protein fold correctly and recover some activity

Question 11

Miglustat

Answer 11

drug treatment for Gaucher type 1, inhibits the

formation of glycosphingolipids and this is called “substrate reduction”

Question 12

role of copper in metabolism

Answer 12

used in lysyl oxidase (collagen)
tyrosinase (melanin synthesis)
cytochromes (ETC)
superoxide dismutase (ROS)

forms ceruloplasmin in the liver
copper transport protien
helps in iron metabolism

Question 13

The life of copper

Answer 13

copper is transported to the liver via albumin

forms ceruloplasmin in the liver and then secreted into plasma (requires copper transporting ATPase)

aged ceruloplasmin is taken up by liver and secreted into the bile (copper transporting ATPase)

Question 14

role of ceruloplasmin and iron metabolism

Answer 14

ceruloplasmin (ferroxidase) converts ferrous iron to the ferric form

incorporates the ferric ion into transferrin

mobilizes ferric ions from ferritin and hemosiderin

acute phase protein

Question 15

copper deficiency

Answer 15

microcytic anemia (smaller RBCs) 
less iron mobilization 

degradation of vascular tissue (decreased lysyl oxidase activity)
increased risk of bleeding

defects in pigmentation of hair

Question 16

Menkes syndrome

Answer 16

inherited defect of dietary copper absorption
lower plasma copper levels
X-linked recessive disorder

hair is twisty and grayish
aneurysms and neurological dysfunction
early age of presentation (1-2 years)

Question 17

Wilson’s disease

Answer 17

autosomal recessive disorder
accumulation of copper in liver, brain, and eye

mutation of copper transporting ATPase (no excretion of copper into bile)

kayser-fleischer rings (eye) (will have basal ganglia involvement)
neurological damage
hepatitis and cirrhosis

labs:
decreased ceruloplasmin
increased urinary excretion of copper
increased hepatic copper content

Question 18

role of iron

Answer 18

heme synthesis
RBC’s contain iron

for redox reactions and component of ETC

Question 19

lab test for iron levels

Answer 19

high serum ferritin = iron overload (hemochromatosis)
low serum ferritin = iron deficiency anemia

TIBC:
total number of iron binding sites on transferrin

high TIBC = iron deficiency
low TIBC = iron overload

normal = 30% saturation

Question 20

iron deficiency anemia

Answer 20

most common nutritional deficiency

can be seen in those:
reduced intake of iron
infants, pregnant women, blood donors
chronic bleeding

clinical features: 
hypochromic microcytic 
fatigue and pallor 
weakness / dizziness
brittle nails 
pica

Question 21

iron deficiency labs

Answer 21

low serum ferritin 
low iron levels 
low saturation  (less than 20%) 
low hemoglobin levels 
bone marrow iron stores are low 
Low MCV and low MCHC

Question 22

Hereditary Hemochromatosis (Iron overload)

Answer 22

autosomal recessive disorder
common in white people

over absorption of iron (HFE gene mutation)
allelic heterogenicity and compound heterozygotes are present

delayed onset
males affected more

excessive accumulation of iron in skin, liver, and pancreas

Question 23

hereditary hemochromatosis sign/symptoms

Answer 23

excessive iron leads to free radical formation and DNA damage

more common in males around age 40 
will have chronic joint pain 
chronic fatigue
hepatomegaly 
diabetes 
cardiac dysfunction 
brownish skin pigmentation

Question 24

hereditary hemochromatosis labs

Answer 24

high serum ferritin levels
high serum iron levels
transferrin saturation (more than 50%)
TIBC is decreased

Question 25

hemochromatosis management

Answer 25

phlebotomy- removal of blood 
dietary modifications (less iron)

Question 26

Nutritional anemia

Answer 26

anemia is a clinical sign
reduced red cell mass
hemoglobin levels are low and RBC’s are low

reduced nutritional needs

Question 27

microcytic anemia

Answer 27

due to reduced heme synthesis

deficiency in iron (most common)
deficiency in copper
deficiency in B6

Question 28

macrocytic anemia

Answer 28

due to reduced cell division

deficiency in B12
deficiency in folate

Question 29

normocytic anemia

Answer 29

protein-calorie deficiency (PEM)

Question 30

Microcytic anemia: Iron deficiency labs

Answer 30

serum ferritin levels are low
serum iron low
microcytic RBC’s and hypochromatic RBC’s

vitamin C deficiency is a risk factor

Question 31

Microcytic anemia: Vitamin B6 deficiency labs

Answer 31

vitamin B6 is needed for heme synthesis (ALA synthase)

iron is normal
homocysteine levels are high
hypochromic microcytic anemia
sideroblasts

Question 32

Microcytic anemia: Copper deficiency

Answer 32

reduced ceruloplasmin levels

defect in iron metabolism

Question 33

Macrocytic megaloblastic anemia

Answer 33

cytosol enlargement after DNA synthesis
hypersegmentation of neutrophils

seen in Vit B12 or folate deficiency