Disorders/Diseases Flashcards
Von Gierke’s Disease (Type 1 GSD)
Discuss cause, Sx, and Tx
a. Glucose-6-Phosphatase deficiency.
b. Liver unable to regulate blood glucose in response to epinephrine and glucagon. Hypoglycemic occurs after short fast. Results in liver enlargement, neurological impairment (brain does have enough glucose.
c. Treatments
(1) Dietary: low carb meals, eat frequent small meals.
(2) Transposition of potal vein: more glucose rich blood to systemic circulation.
(3) Liver transplant: most effective.
Cori’s Disease (Type III GSD)
Discuss cause, Sx, and Tx.
a. Amylo-1,6-glucosidase deficiency (Debranching enzyme).
b. Results in glycogen of abnormal structure; numerous short branches. Inefficient breakdown of glycogen→ Hypoglycemia.
c. Treatment primarily through diet: limit glycogen storage. Symptoms often disappear at puberty though can become more sedentary→ obesity. Hypoglycemic on exercise. Not as severe as von gierke’s.
Anderson’s Disease (Type IV GSD)
Discuss Cause, Sx, and Tx.
a. Amylo-(1,4→1,6)-transglycosylase (Branching Enzyme).
b. Results in accumulation of glycogen of abnormal structure. Auto-immune response. Rarely live past age 5 without liver transplant.
McArdle’s Disease (Type V GSD)
Discuss Cause, Sx, and Tx.
a. Deficiency in muscle phosphorylase.
b. Results in inability to brek down glycogen in muscle, but liver phosphorylase is unaffected. Cramps at onset of exercise, but subside with “second wind” (liver breaks glycogen down to glucose→ blood).
Her’s Disease
Discuss Cause, Sx, and Tx.
a. Liver phosphorylase deficiency
b. Sx intermediate between Von Gierke’s and Cori’s disease.
c. Effectively treated with dietary changes.
Fructose intolerance
Discuss types, Cause, for each Sx for each, and Tx.
a. Benign: Deficiency in Fructokinase. Excess fructose in urine.
b. Hereditary: deficiency of Type B Aldolase.
(1) Large amounts of fructose in liver result in phosphate depletion, liver failure can occur. Tend to develop distate for sweets (self-regulating)
Galactosemia
Discuss types. Cause, Sx, and Tx for each.
a. Type I: Deficiency in UDP-Galactose Udidydyl Transferase. Results in buildup of Galactose-1-phosphate→ accumulation of Galacititol. Leads to cataracts, vomiting, liver failure, mental retardation. Treated with diet to avoid galactose.
b. Type II: Deficiency in galactokinase. Results in buildup of galactose→ excreted in urine. Can also get cataracts due to Galacititol buildup. Requires galactose free diet.
c. Type II: Deficiency in UDP-Galactose-4-epimerase along with lower activity of either GALT or GALK→ severe neuro affects.
Pyruvate Carboxylase Deficiency
Describe mechanism and acute sx
Describe chronic sx associated with differences and origins of Type A, B, and C.
Can’t convert Pyruvate to Oxaloacetate.
Acute: hypoglycemia, tachypnea resulting from lactic acidosis, and ketoacidosis.
a. Type A (North American) Presents in infancy with mental retardation, developmental delays, and survival until early adulthood.
b. Type B (French): Neonatal presentation, severe neurodegeneration and developmental delays. Some cases of anencephaly. Usually fatal within first year of life.
c. Type C (Benign): near normal activity. Often only acute symtoms with no neuro or physical developmental delays.
Pyruvate Dehydrogenase deficiency
Describe mechanism, acute sx, chronic sx.
- Inability to convert Pyruvate to Acetyl Co-A effectively.
- Acute sx: lactic acidosis and ketoacidosis, but NOT hypoglycemia.
- Chronic sx: severe neurodegeneration and developmental delays.
- Thiamine responsive type is similar to thiamine responsive form of maple syrup disease (E1 lowers binding constant of TPP).
ETC Chain Deficiencies
Complex I and II sx.
a. Leukodystrophy accompanied by Parnkinsonian-like sx.
b. Leigh’s syndrome.
c. Cardiac dysfunction.
d. Small % respond to riboflavin treatment.
Gaucher Disease
What enzyme is affected?
What does this cause?
Describe the 3 Classifications
- Deficiency in -glucosidase (glcocerbrocidase)
- Results in accumulation of glucocerbrosides in spleen, liver, lungs, kidney, brain, and bone marrow. Common sx include enlarged spleen and liver, painful bone lesions, and severe neurological dysfunction.
Type I (nonneuropathic): Western German and Ashkenazi jews. Least severe, doesn’t affect brain.
Type II (acute infantile neuropathic): extensive brain damage at early age, spasm, liver and spleen failure. Death by age 2.
Type II (chronic neuropathic: childhood or adult onset. Less severe but still progressive brain damage. Live into teens and adulthood. Common in Nordic pop.
Neimann-Pick Disease
What enzyme is affected?
What does this cause?
Describe the 4 Classifications.
- Deficiency in sphingomyelinase.
- Results in accumulation of sphingomyelin. Affects spleen, liver, bone marrow, lungs, and brain.
- Types A+B affected y mutations on same gene.
- C and D are same mutation. D is Nova Scotian ancestry.
Tay-Sachs Disease
What enzyme is affected?
What does this cause?
What are the 2 main types?
- Deficiency in B-hexosaminidase
- Results in accumulation of Glangliosides (GM2).
Infantile Tay-Sachs (most common): leads to progressive neurodegeneration. Typically fatal by age 5.
Late Onset (LOTS): progresses much slower. Manageable sx.
Huntington Disease (HD)
Type of Inheritance?
Gene affected?
Presentation?
-Autosomal dominant inheritance
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Neurofibromatosis Type I
Type of Inheritance?
Gene affected?
Presentation?
-Autosomal dominant inheritance
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