Inborn errors of fat metab

Question 1

GSD 0 - Hepatic glycogen synthase deficiency

Answer 1

indiv cannot make glycogen
- rely solely on gluconeogenesis for glucose production

Sx:

• hyperglycemia after meal
• fasting hypoglycemia
• increased lactate
• severe ketotic hypoglycemia

Only GSD without liver enlargement on exam

Question 2

GSD-1 Glucose-6-phosphatase deficiency

Answer 2

profound DEFECT in hepatic glucose production during fasting

• can form glycogen, but cannot leave liver as glucose
• liver is dramatically enlarged with glycogen
• lactic acidosis
• hypertriglyceridemia

Question 3

Most severe glycogen storage disease

Answer 3

Glucose-6-phosphatase deficiency

GSD-1

Question 4

how does GSD I usually present?

Answer 4

glucose 6-phosphatase deficiency

• infants usually in the first year of life with:
• severe fasting hypoglycemia w/in 3-4 hours after a meal

tx: constant supply of oral glucose
- widely spaced feedings

Question 5

Debranching enzyme deficiency (GSD IV)

Andersen disease

Answer 5

• very rare
• abnl unbranched glycogen accum in liver and muscle
• WEAKNESS due to myopathy induced by abnl glycogen
• HEPATOMEGALY

(liver injury –> progressive liver injury –> cirrhosis –> death b4 age 6)

Question 6

GLycogen storage disease

Answer 6

GSD I: Glucose 6 Phosphatase deficiency

Question 7

Glycogen synthesis disorders

Answer 7

GSD 0 - Hepatic Glycogen synthease deficiency

GSD IV - Branching enzyme def (Andersen disease)

Question 8

Glycogen breakdown disorders

Answer 8

GSD VI: Phosphorylase def
GSD IX: phosphorylase kinase def
GSD III: debranching enzyme def (Cori disease)

Question 9

Gluconeogenic disorder

Answer 9

Fructose 1-6 bisphosphatase def

Question 10

Disorders of Fructose and Galactose metab

Answer 10

Hereditary fructose intolerance

Galactosemia

Question 11

Disorders of fat oxidation

Answer 11

Medium chain acyl coA dehydrogenase def (MCAD)

VLCAD

CPT-1 Def

Question 12

Phosphorylase def (GSD VI) +
Phosphorylase Kinase def (GSD IX)

Answer 12

(25-30% of GSD)

Not as effective as degrading Glycogen

Milder than G6-phosphatase def
- gluconeo, lypolysis, FA oxid and ketogenesis intact!

Hepatomegaly
Short stature
mild muscle weakness

Question 13

Debranching enzyme deficiency (GSD III, Cori disease)

Answer 13

Accum of abnl glycogen in liver and muscle

Milder than G 6 Phosphatase def
(improves clinically by adulthood)

• Hepatomegaly
• Hypoglycemia
• nl lactate + uric acid lvl
• delayed growth/short stature
• myopathy
• increased ketones

Question 14

Fructose 1,6 bisphosphatase def

Answer 14

defect in key step!

Late hypoglycemia following FASTING for 18-24hours
- glycogen breakdown + form nl

No hepatomegaly

Severe lactic acidosis
- results in compensatory respiratory alkalosis (hyperventilation)

Increased lvls of pyruvate (lots converge)

Hypoglycemia –> ketones elevated

Question 15

Hereditary fructose intolderance

Answer 15

Fructose is metabolized to F1P (by fructokinase)

F1P is metabolized to glyceraldehyde (3C) that enters glycolysis BELOW THE KEY STEP (F1,6BP) (By aldolase B!!!)

Lack aldolase B –>
accumulate F1P –>
inhibits glycogenolysis AND gluconeogenesis –>
hypoglycemia

sx: during fructose/fruit intro into diet
(n/v, pallor, coma)
- elevated LFTs

Question 16

Galactosemia

Answer 16

deficiency in GALT
- unable to metabolize galactose when milk is introduced

Build up of galactose –> liver injury –>
Jaundice, coag disturbances, cataracts, ataxia, tremor, speech impairment

Question 17

lab eval of HYPOGLYCEMIA

Answer 17

take critical samples of blood and urine at time of hypoglycemia,

dont take after beginning treatment
- answer is in the blood