Biochemistry disorders Flashcards
What is maple syrup urine disease? (Cause, enzyme defect, transmission type, symptoms, treatment)
Blocked degradation of branched amino acids (Isoleucine, Leucine, Valine)
Decreased alpha-ketoacid dehydrogenase (B1).
Increased alpha-ketoacids in the blood, especially those of leucine.
Symptoms: severe CNS defects, intellectual, disability, and death
Autosomal recessive.
Urine smells like maple syrup/burnt sugar
Tx: restriction of leucine, isoleucine, and valine in diet + thiamine supplementation
What is glycogen phosphorylase and how is it regulated?
It cuts glucose-1-P off of chains until it is 4 residues from a branch point. it is regulated by glycogen phosphorylase kinase (phosphorylating it activates it) which is activated by epinephrine and glucagon.
What are the four glycogen storage disorders?
Very Poor Carbohydrate Metabolism: Von Gierke Disease (Type I) Pompe Disease (Type II) Cori disease (Type III) McArdle Disease (Type V)
What is Von Gierke disease?
Type I.
Severe fasting hypoglycemia, A lot of increased glycogen in liver, increased blood lactate, hepatomegaly.
Deficient enzyme: Glucose-6-phosphatase
Autosomal recessive.
Treatment: frequent oral glucose/cornstarch; avoidance of fructose and galactose.
What is Pompe disease?
Type II.
Cardiomyopathy and systemic findings leading to early death.
Deficient enzyme: Lysosomal alpha-1,4-glucosidase (acid maltase)
Autosomal recessive.
Pompe trashes the pump (heart, liver, muscle).
What is Cori disease?
Type III. Milder form of type I with normal blood lactate levels. Deficient enzyme: debranching enzyme. Autosomal recessive. Gluconeogenesis is intact.
What is McArdle Disease?
Type V.
Increased glycogen in muscle, but cannot break it down, leading to painful muscle cramps, myglobinuria (red urine) with strenuous exercise, and arrhythmia from electrolyte abnormalities.
Deficient enzyme: skeletal muscle glycogen phosphorylase (myophosphorylase).
Autosomal recessive.
McArdle = muscle.
What is Fabry disease?
Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease
Deficient enzyme: alpha-galactosidase A
Accumulated substrate: Ceramide trihexoside
X-recessive
What is Gaucher disease?
Most common.
Hepatosplenomegaly, pancytopenia, aseptic necrosis of femur, bone crises, Gaucher cells (lipid laden macrophages resembling crumpled tissue paper);
treatment: recombinant glucocerebrosidase
Deficient enzyme: Glucocerebrosidase (B-glucosidase)
Accumulated substrate: Glucocerebroside
Autosomal recessive
What is Niemann-Pick disease?
Progressive neurodegeneration, hepatosplenomegaly, “cherry-red” spot on macula, foam cells (lipid-laden macrophages).
Deficient enzyme: sphingomyelinase
Accumulated substrate: sphingomyelin
Autosomal recessive
No man picks (Niemann-Pick) his nose with his sphinger (sphingomyelinase)
What is Tay-Sachs disease?
Progressive neurodegeneration, developmental delay, "cherry-red" spot on macula, lysosomes with onion skin, no hepatoslenomegaly used for differentiating between Niemann-Pick. Deficient enzyme: hexosaminidase A Accumulated substrate: GM2 ganglioside Autosomal recessive Tay SaX lacks heXosaminidase.
What is Krabbe disease?
Peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Deficient enzyme: galactocerebrosidase
Accumulated substrate: galactocerebroside, psychosine (buildup destroys myelin sheath)
Autosomal recessive
What is metachromatic leukodystrophy?
Central and peripheral demyelination with ataxia, dementia.
Deficient enzyme: Arylsulfatase A
Accumulated substrate: Cerebroside sulfate (leads to impaired production of myelin sheath)
Autosomal recessive.
What is Hurler Syndrome?
Mucopolysaccharidoses.
Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly.
Deficient enzyme: alpha-L-iduronidase.
Accumulated substrate: Heparan sulfate, dermatan sulfate.
Autosomal recessive.
What is Hunter syndrome?
Mucopolysaccharidoses.
Mild Hurler + aggressive behavior, no corneal clouding.
Deficient enzyme: Iduronate sulfatase
Accumulated substrate: Heparan sulfate, dermatan sulfate.
X-recessive.
Hunter’s see clearly (no corneal clouding) and aggressively aim for the X.
Which Lysosomal storage disorders occur more frequently with Ashkenazi Jews?
Tay Sachs, Niemann-Pick, Gaucher disease
What is Type 1 hyperchylomicronemia?
Increased Chylomicrons, TG, cholesterol.
Autosomal recessive.
Lipoprotein lipase deficiency or altered apolipoprotein C-II cause pancreatitis, hepatosplenomegaly and eruptive /pruritic xanthomas (no increased risk for atherosclerosis).
What is type IIa - familial hypercholesterolemia?
Increased LDL, cholesterol.
Autosomal dominant.
Absent or defective LDL receptors.
Heterozygotes (1:500) have cholesterol + 300mg/dL; homozygotes have very high cholesterol ~ 700. Causes accelerated atherosclerosis (May have MI before age 20), tendon (Achilles) xanthomas, and corneal arcus.
What is type IV - hypertriglyceridemia?
Increased VLDL, TG.
Autosomal dominant.
Hepatic overproduction of VLDL. Causes pancreatitis.
What is type III - familial dysbetalipoproteinemia?
Increased cholesterol, TGs.
ApoE3/E4 defect
Xanthomas. Premature coronary/vascular disease.
What are the mnemonics for all the lysosomal disorders?
All are autosomal recessive except Fabry and Hunter XR. Hunger pointing gun to X target. Hurler is like Hunter (both mucopolysaccharidoses), but Hurler can’t hunt well because of corneal clouding. Both Hunter and Hurler accumulates Heparan Sulfate (and dermatan sulfate). Hurler is alpha-iduronidase deficiency (remember that and the other one should be easy - iduronate sulfatase)
No man picks his nose with his Sphinger “Nieman Pick - Sphingomyelinase “
Gaucher-Glucocerebrosidase-Glucocerebroside 3G… have you Got your iPhone 3G. Gaucher Cells are crumpled tissue paper macrophages.
Cherry-red spot is hyphenated and so is Nieman Pick and Tay-Sach
Ashkenazi Jews have Gaucher, Niemann-Pick, and Tay-Sachs
Angiokeratoma is a Fabric of Vessels and Galaxy of skin spots. Angiokeratoma is seen in Fabry disease in which there is a Galactosidase deficiency and epidermal keratosis. Ceramide trihexoside accumulates (fabric of vessels through brain…think cerebral..which is ceramide trihexoside).
Tay-Sachs..Tay is a kid who crashes his GM car…GM2 ganglioside accumulates.
What is abetalipoproteinemia?
It’s a defect in Apo B synthesis (decreased). Problem secreting chylomicrons and VLDL into bloodstream and so fat accumulates into enterocytes. Mutation in microsomal triglyceride transfer protein (MTP). ApoB-100 is VLDL and ApoB-48 is for chylomicrons.
Symptoms are failure to thrive, steatorrhea, acanthocytosis, ataxia and night blindness (these last two are from lack of Vitamin E).
