Block 2 Clinical Correlations

Question 1

Thiamine deficiency

Answer 1

Wernicke-Korsakoff Syndrome

Question 2

PDH deficiency
Pyruvate can’t enter TCA cycle, so it’s converted to lactic acid
Treated via ketogenic diet, since ketones are the second major energy source in the brain

Answer 2

Leigh syndrome/congenital lactic acidosis

Question 3

Inhibits pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex, which require lipoic acid as a cofactor

Answer 3

Arsenic poisoning

Question 4

Primary arsenic poisoning

Answer 4

Arsenic converted to arsenite, which complexes with thiol groups on lipoic acid, stopping TCA
Most severe

Question 5

Secondary arsenic poisoning

Answer 5

G3P complexes with arsenic, inhibiting one of the energy generating steps in the glycolytic pathway
Primarily affects brain

Question 6

Rat poison (fluoroacetate)

Answer 6

Fluoroacetate–>fluoroacetyl CoA + oxaloacetate–>Fluorocitrate (inhibits aconitase)

Question 7

Deficiency in skeletal muscle glycogen phosphorylase
Autosomal recessive
Intolerance to exercise, chronic muscle cramps
Transient myoglobinemia and myoglobinuria folloing exercise due to rhabdomyolysis
Serum glucose regulation normal
Relatively benign with progressive muscle weakness and atrophy with fatty replacement

Answer 7

McArdle Disease

GSD V

Question 8

Defect in liver glycogen phosphorylase
Autosomal recessive
Mild to moderate hypoglycemia, mild ketosis, and prominent hepatomegaly
Muscle and heart are unaffected, good prognosis

Answer 8

Her’s disease

GSD VI

Question 9

Defect in liver/muscle or liver debranching enzyme
Autosomal recessive
Results in accumulation of glycogen with short outer chains
Hepatomegaly, hypoglycemia, growth retardation, and cardiomyopathy

Answer 9

Cori (Forbes) disease

GSD III

Question 10

Lysosomal storage disease resulting from an inherited defect in a(1,4) glucosidase
Autosomal recessive, rare
Infantile onset (classic)
Cardiomyopathy and muscle hypotonia
Experimental enzyme replacement therapy (recombinant form of human a(1,4) glucosidase modified with mannose-6-phosphate to facilitate phagocytic uptake of enzyme into lysosomes)

Answer 10

Pompe disease

GSD II

Question 11

G6Phosphatase deficiency (type Ia)
G6Phosphatase translocase deficiency (type IIb)
Severe hypoglycemia following exercise or short-term fast
Lipidemia results from shunting of excess G6P to triglyceride synthesis
Better prognosis now

Answer 11

Von Gierke disease

GSD I

Question 12

Clinically heterogenous inherited deficiency in branching enzyme
Can’t mobilize glycogen very well
Presents with failure to thrive, hepatosplenomegaly, deposition of abnormal glycogen with low brinching, and liver cirrhosis
Mortality by age 5

Answer 12

Andersen disease

GSD IV