Diseases and Disorders Exam 4

Question 1

Hereditary Fructose Intolerance

Answer 1

• deficiency of aldolase B
• leads to an accumulation of fructose 1-P in the liver and kidney
• sx first appear when baby is weaned from milk
• leads to inhibition of glycolysis, decreased hepatic ATP, inhibited gluconeogenesis, hypoglycemia, lactic acidosis
• remove fructose from diet to prevent liver failure and possible death

Question 2

Essential Fructosuria

Answer 2

• genetic deficiency in fructokinase KHK gene
• fructose can’t be converted to fructose 1-P
• fructose accumulates in the urine
• is benign

Question 3

Lactase Deficiency

Answer 3

• inability to digest lactose
• leads to watery diarrhea and gas
• can be genetic, age related or from injuries to the mucosa
• may have trouble digesting lactose after periods of severe food poisoning or diarrhea.

Question 4

Acarbose

Answer 4

• drug that blocks pancreatic alpha-amylase and brush-border alpha-glucosidases
• can be used to treat DM2 by reducing the rate at which ingested carbs reach the blood stream
• gas and diarrhea are common side effects so it is not used very often

Question 5

Mutations in SGLT1

Answer 5

malabsorption of glucose and galatose

Question 6

Mutations in SGLT2

Answer 6

familial renal glycosuria

Question 7

Inhibitors of SGLT2 (gliflozins)

Answer 7

• used to treat DM2
• SGLT2 can only reabsorb up to 200 mg/dl of glucose, over that it is peed out
• thus inhibiting SGLT2 will increase glucose excretion in the urine

Question 8

Neonatal Diabetes (MODY)

Answer 8

• mutation in KCNJ11 gene which codes for a subunit of the K-ATP channel
• leads to the channel being permanently open and prevents the release of insulin from pancreas
• can be treated with sulfonylureas which close the K channel

Question 9

GLUT1 Deficiency Syndrome

Answer 9

• decreased glucose transport into the CSF and the brain

- pts with seizures and developmental delays

Question 10

Lactic Acidosis

Answer 10

• Excess lactic acid in blood (>5mM) which decreases the pH (<7.2)
• Caused by increased NADH/NAD+ ratio which prevents pyruvate from entering the TCA cycle so it becomes lactate
• causes are excess alcohol, hypoxia, genetic

Question 11

Mercury and Arsenic Poisoning

Answer 11

• inhibit glyceraldehyde 3-P dehydrogenase
• mercury inactivates
• arsenite subs for Pi in rxn
• prevents glycolysis

Question 12

Deficiency of pyruvate kinase or phosphoglycerate kinase

Answer 12

• depletes cells of ATP
• osmotic balance is messed up
• RBCs swell and burst -> hemolytic anemia

Question 13

Hyperglycemia and Sorbitol

Answer 13

• in uncontrolled DM, lots of glucose enters the lens, retina, nerve and kidneys
• glucose is converted to sorbitol
• these cells lack sorbitol dehydrogenase to make fructose
• sorbitol accumulates, and causes cells to swell

Question 14

Galactokinase and GALT Deficiencies

Answer 14

• when galactose accumulates in cells, aldose reductase reduces it to galactitol
• this can lead to cataracts very early in life, vomiting and diarrhea after consuming galactose, liver damage and mental retardation

Question 15

G6PD Deficiency

Answer 15

• one of most common genetic diseases
• X linked
• usually only causes problems when under increased oxidative stress
• affected individuals show Heinz bodies in their RBCs which are clumps of denatured proteins

Question 16

Classes of G6PD Deficiency

Answer 16

• Class I: most severe, anemia even in absence of stress
• Class II (Mediterranean): severe, enzyme with reduced stability
• Class III (A): moderate, oldest cells have reduced enzyme activity and lyse
• Class IV: no clinical sx

Question 17

GSD 0

Answer 17

• Disorder name: n/a
• Enzyme: glycogen synthase
• Organ: liver
• Pathway: glycogenesis chain enlongation
• Manifestation: hypoglycemia, failure to thrive, early death

Question 18

GSD I

Answer 18

• Disorder name: von Gierke
• Enzyme: glucose 6-phosphatase
• Organ: liver
• Pathway: glycogenolysis/gluconeogenesis: dephosphorylation of glucose 6-P to glucose
• Manifestation: enlarged liver and kidney, growth failure, fasting hypoglycemia, acidosis, lipidemia, thrombocyte dysfunction

Question 19

GSD II

Answer 19

• Disorder name: Pompe
• Enzyme: acid maltase
• Organ: all with lysosomes
• Pathway: lysosomal glycogenolysis: release of Glc
• Manifestation: in infants - progressive muscle hypotonia, cardiac failure and death before age 2.
  in juveniles - myopathy and variable cardiac involvment
  in adults: muscular dystrophy like features, glycogen deposits with short outer branches

Question 20

GSD III

Answer 20

• Disorder name: Cori
• Enzyme: Debranching enzyme
• Organ: liver, skeletal muscle, heart
• Pathway: Glycogenolysis: Glc cleavage and release from branch point
• Manifestation: fasting hypoglycemia, hepatomegaly in infants and some myopathy. Glycogen deposits have short outer branches

Question 21

GSD IV

Answer 21

• Disorder name: Andersen
• Enzyme: Glucosyl (4:6) transferase (branching enzyme)
• Organ: liver
• Pathway: glycogenesis: chain branching
• Manifestation: hepatosplenomegaly, usually fatal

Question 22

GSD V

Answer 22

• Disorder name: McArdle
• Enzyme: muscle glycogen phosphorylase
• Organ: skeletal muscle
• Pathway: glycogenolysis: Glc 1-P release
• Manifestation: exercise induced muscle pain, cramps and progressive weakness

Question 23

GSD VI

Answer 23

• Disorder name: Hers
• Enzyme: liver glycogen phosphorylase
• Organ: liver
• Pathway: glycogenolysis: Glc 1-P release
• Manifestation: hepatomegaly, mild hypoglycemia, good prognosis

Question 24

GSD VII

Answer 24

• Disorder name: Tarui Syndrome
• Enzyme: PFK-1
• Organ: muscle, RBCs
• Manifestation: exercise induced muscle pain, cramps and progressive weakness, enzymopathic hemolysis

Question 25

GSD XI

Answer 25

• Disorder name: Fanconi-Bickel Syndrome
• Enzyme: GLUT 2
• Organ: intestine, pancreas, kidney, liver
• Manifestation: glycogen accumulation in liver and kidney, rickets, growth retardation, glucosuria

Question 26

Neonatal Hypoglycemia

Answer 26

• when newborn is cut off from mothers glucose, will become hypoglycemic and epi and glucagon will stimulate the liver to begin glycogenolysis.
• if newborn lacks glycogen stores can be life-threatening
• if mother had unontrolled DM, baby will have high glycogen stores and insulin levels. will not be stimulated by glucagon to begin glycogenolysis