MCM Diseases

Question 1

Niemann-Pick Disease

Answer 1

Cause: deficiency in activity of A-SMase.
A-SMase breaks down sphingomyelin.
Leads to hepatomegaly, splenomegaly, and hallmark cherry spot in the eye.

Question 2

Erythroblastosis fetalis

Answer 2

Mother is Rh- and fetus is Rh+. Mom makes ABs against fetus’ RBCs.

Question 3

Spur Cell Anemia

Answer 3

Elevated cholesterol in RBCs, causing rigidity. RBCs lyse as they pass through splenic capillaries, causing hemolytic anemia.

Question 4

Cystic Fibrosis

Answer 4

Mutation in CFTR gene. Cl- cannot leave epithelium, causing an increase in NaCl. Water follows, causing thic secretions and increase RTIs.

Question 5

Cystinuria

Answer 5

Defect in transport of Cysteine (and Arg, Lys, Orn). Results in cysteine stones in the kidney.

Question 6

Hartnup Disease

Answer 6

Defect in transport of for nonpolar and uncharged AAs (think Trp and its derivatives). Leads to lack of muscle control, photodermatitis, photosensitivity.

Question 7

Cardiotonic drugs and HF

Answer 7

Cardiotonics inhibit the Na/K pump and lead to an increase of Ca2+ inside the cell (think about why this would happen). Increases contraction.

Question 8

Components of TEE (4)

Answer 8

BMR =/= RMR
Thermic affect of food (digestion)
Physical activity
Non-exercise induced thermogenesis

Question 9

Vit B1

Answer 9

Thiamine
Coenzyme in many metabolic pathways (glcolysis, TCA, PPP non-ox phase)
Wernicke’s (ataxia), Korsakoff’s (psychosis), dry beriberi (muscle wasting), wet beriberi (HF).

Question 10

Vit B2

Answer 10

Riboflavin
FAD/FMN
Corneal neovasularization, cheilosis, magenta colored tongue.

Question 11

Vit B3

Answer 11

Niacin
NADH/NADPH (synthesized from W)
Hartnup disease can cause deficiency.
Manifests as Pellagra.

Question 12

Vit B5

Answer 12

Pantothenic acid
CoA
Dermatitis, numbness, parasthesia, cramps, hypoglycemia.

Question 13

Vit B6 (no manifestations)

Answer 13

Pyridoxine

ALT, AST

Question 14

Vit B7

Answer 14

Biotin
Cofactor for carboxylation enzymes. (in GNG, FA synthesis)
Alopecia, rashes, bowel inflammation, muscle pain.

Question 15

Vit B9

Answer 15

Folic acid
de novo pyrimidine synthesis.
Anemia, homocysteinemia.

Question 16

Vit B12

Answer 16

Cobalamin
Coenzyme for homocysteine metyltransferase and methylmalonyl- CoA mutase.
Manifests as anemia, neuropathy, homocysteinemia.

Question 17

Vit C

Answer 17

Ascorbate
Cofactor for colagen synthesis, norepi synthesis, Fe absorption.
Manifests as Scurvy

Question 18

Vit A and deficiency origin

Answer 18

Retinol, retinoic acid, retinal.
Deficient from malabsorption, fat malabsorption and cirrhosis.
Maintains vision and epithelium.

Question 19

Vit D (function, disease, symptoms)

Answer 19

Calcitriol.
GI (synthesize Ca2+), kidneys (reabsorption of Ca 2+), bone (bone resorption). All about Ca 2+!
Rickets.
Delayed growth, muscle pain/weakness, bowed legs.

Question 20

Diabetes (I and II)

Answer 20

Type I: insulin deficiency due to loss of beta cells.

Type II: insulin resistance due to loss of beta cell function.

Question 21

Tarui Disease

Answer 21

PFK-1 deficiency.

Mild but can cause muscle cramps and h. anemia.

Question 22

F 1,6 BP deficiency

Answer 22

Similar to Tarui, but in GNG.

Can cause hypoglycemia, lactic acidosis.

Question 23

Von Gierke Disease

Answer 23

Glucose 6-phosphatase deficiency.

Hypoglycemia, lactic acidosis, hepatomegaly (due to build up of glycogen).

Question 24

Fanconi-Bickel syndrome

Answer 24

Mutation in GLUT 2. Unable to take in glu, gal, fru.
Failure to thrive, hepatomegaly, rickets.
Treat with Vit D.

Question 25

GALT deficiency

Answer 25

Leads to accumulation of galactitol. | Can cause failure to thrive, liver failure, sepsis, bleeding.

Question 26

Galactokinase deficiency

Answer 26

Leads to accumulation of gal and galactitol in blood and urine. Can cause early cataracts.

Question 27

GSD 0

Answer 27

Defective enzyme: glycogen synthase | Pathway affected: chain elongation

Question 28

GSD II | Pompe Disease

Answer 28

Defective enzyme: acid maltase | Pathway affected: lysosomal glycogenolysis - cannot release glc.

Question 29

GSD III | Cori Disease

Answer 29

Defective enzyme: debranching enzyme | Pathway affected: glc cleavage and release from branch point.

Question 30

GSD IV | Andersen Disease

Answer 30

Defective enzyme: glucosyl 4:6 transferase | Pathway affected: chain branching

Question 31

GSD V | McArdle Disease

Answer 31

Defective enzyme: muscle glycogen phosphorylase | Pathway affected: glc 1-P release

Question 32

GSD VI | Hers Disease

Answer 32

Defective enzyme: liver glycogen phosphorylase | Pathway affected: glc 1-P release

Question 33

2-oxoglutaric aciduria

Answer 33

d/o of TCA. Causes developmental delay and severe neurological problems in infants (metabolic acidosis, microcephalopathy, mental retardation).

Question 34

Fumarase deficiency

Answer 34

d/o of TCA Causes severe neurological impairment. Fatal within 2 years. Also causes encephalopathy, dystonis, increased urinary output of fumarate, succinate, citrate and a-KG.

Question 35

Succinyl-CoA synthetase (SCS) deficiency

Answer 35

Mutations in 2 of 3 subunits (SUCLA2 and SUCLG1). Predictable pattern of dytonia and deafness. Genetic testing can help diagnose.

Question 36

Mitochondrial depletion syndrome

Answer 36

Severe hypotonia, progressive dystonia, muscular atrophy, and severe sensory impairment.

Question 37

Luft's Disease

Answer 37

Increased metabolic function with normal thyroid activity. Caused by uncoupled ox-phosp, high levels of cytochrome c and low levels of Q

Question 38

Primary causes of mitochondrial diseases (2)

Answer 38

Defect in nuclear DNA encoding mitochondrial proteins. | Defect in mitochondrial DNA

Question 39

Secondary causes of mitochondrial diseases

Answer 39

Ischemia, repefusion, CVD, renal failure, drugs, alcohol, smoking.

Question 40

Clinical features of mitochondrial diseases

Answer 40

Nervous system, eyes, skeletal muscle, heart

Question 41

Metabolic features of mitochondrial diseases (3)

Answer 41

Low energy production. Increased free radical production. Lactic acidosis.

Question 42

MCAD deficiency

Answer 42

Impairs breakdown of MCFAs, leading to secnodary carnitine deficiency. FA accumulates in liver, interferes with urea cycle and increases levels of ammonia. Patients must depend on Glu for energy.

Question 43

Homocystinuria

Answer 43

Caused by defective cystathione b-synthase or Vit B6 deficiency. Increases levels of homocysteine, but can be helped by Vit B6 supplementation. Mostly affects eyes, skeleton, CNS and vascular system.

Question 44

MSUD

Answer 44

Deficienct BCKD cannot breakdown L,I,V. Blood accumulates in brain and can cause problems with brain function and eventually mental retardation. Thiamine (VB1) supplements can elp in some mild cases.

Question 45

PKU

Answer 45

Defect in PAH. Phe converted to phenyllactate and phenylacetone instead of Tyr. Can disrupt NT transmission and brain function.

Question 46

Albanism

Answer 46

Defect in tyrosinase.Cannot form melanin from Tyr.

Question 47

Gout

Answer 47

Increase in uric acid which crystalizes in distal parts of the body. Treated with diet change, then allopurinol to block xanthine oxidase.

Question 48

Lesch-Nyhan syndrome

Answer 48

Defect in HGPRT enzyme in purine salvage pathway. Overproduction or uric acid, leading to gout. Commonly causes kidney stones, gout, ataxia, mental retardation and self mutilation.

Question 49

Kwashiokor

Answer 49

Severe protein deficiency. | Edema, light skin, hair thinning, distended abdomen, anemia, fatty liver.

Question 50

Marasmus

Answer 50

Protein and calorie deficiency. Emaciated, chronic diarrhea, RTIs, stunted growth, intellectual disabilities, no energy. Weight is less than 62% expected.

Question 51

Metabolic syndrome

Answer 51

One of: DM, impaired glc tolerance, impaired fasting glc, insulin resistance. Two of: HTN, dyslipidemia, obesity, or microalbuminuria.