Term
| Patient presents with fructokinase deficiency, what disease |
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Definition
| Essential fructosuria, this is a benign condition and there is compensation from hexokinase |
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Term
| Patient presents with buildup of fructose 1 phosphate, hypoglycemia and liver damage, which enzyme is deficienct? |
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Definition
Aldolase B
This is Hereditary fructose Intolerance, and there is a bild up of fructose 1 phosphate due to phosphate trapping
Tx: low fructose high carb diet |
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Term
| patient prsents with fasting glucose hypoglycemia, liver damage, can not fast longer than 12-18 hours |
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Definition
Fuctose 1,6, bisphosphate defieincy
-this is interfering with gluconeogensis of converting Fructose 1,6 bisphsphate into Fructose 6 phosphate |
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Term
| Patient presents with cataract in the eye, mental deficiency, and elevated levels of alanine and aspartate transaminase, which enzyme is deficient |
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Definition
Galactose phosphate uradyl transferase
This is classic galactosemia, so patient cannot convert galactose into glucose
Tx: no galactose in diet
Note: remember that alanine and aspartate transaminase in dx indicates liver damage |
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Term
| Patient took some sort of pharmaceutical and as a result is presenting with hemolytic anemia. Lab results show presence of heinz bodies, what could be wrong? |
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Definition
Drug induced RBC hemolysis; Favism
There is a deficiency in glucose-6-phosphate dehydrogenase, which means that the pentose phosphate pathway has been disturbed. This is important mainly for RBC's because this pathway is their only means of NADH production which is necessary for their cellular antioxidant capabilities. Essentially glutathione is the antioxidant and once it reduces radical compound, it then needs to be reduced by glutathione reductase and NADPH. Without NADPH this cannot be done. |
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Term
| Defect in peroxisome bigenesis |
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Definition
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Term
VLCFA unable to cross the peroxisome membrane
Abnormalities in white matter of the cerebrum
plasmalogens |
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Definition
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Term
| Patient has build up of phytanic acid and exibits neurological problems, which enzyme might be lackign? |
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Definition
alpha hydroxylase
this is refusms disease
Tx: restrict green vegetables (because they contain phytanic acid) ad ruminant milk and meat |
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Term
Patient has deficiency in LPL and apoCII
has epigastric pain, shows both Low LDL and HDL |
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Definition
Type 1 hyperlipidemia (hyperchylomicronemia)
increased chylomicrons
Tx: low fat high carb diet |
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Term
| All 4 LDL receptors are defected, leading to CAD/plaques |
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Definition
type IIa
familial hypercholesterolemia
Heterozygotes= have half the receptors
Hymozygotes= no receptors
Can be treated with statins |
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Term
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Definition
| inhibit HMG CoA reductase |
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Term
| Patient prsents with xanthomas, high cholesterol and is starting to show signs of CAD |
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Definition
| Type III (familial dysbetalipoproteniemia or broad beta disease) Apo E2 homozygous |
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Term
| Patient prsents with an elevated production of VLDL associated with glucose adn hyperinsulinemia. Patient has diabetes mellitus ...why could this result? |
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Definition
Type IV (familial hypertriglyceridemia)
Associated with insulin resistance, obesity, alcohol consmption, progestational hormones |
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Term
| patients lab results show incrased VLDL and chylomicrons and decreased HDL and LDL |
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Definition
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Term
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Definition
| familial hyperalphalipoproteinemia...beneficial to health |
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Term
| increased LDL and delayed clearance of VLDL |
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Definition
type IIb (familial combined hyperlipidemia)
associated with high risk of CAD |
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Term
| Patient presents with accumulation of ganliosides mental retardation and muscle weakness also has veceral involvement....what could this be |
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Definition
| Sandhoff disease which is similar to tay sachs except that it has visceral involvement |
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Term
| Patient presents with increased FA in blood, hypoglycemia, decreased ketones, muscle weakness...lab results show myoglobin and CK in blood and high vLDL what could be the problem |
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Definition
carnitine deficiency or carnitine acyl transferase deficiency
This is the rate limiting step for beta oxidation
Tx: administer high levels of carnitine |
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Term
| Respiratory distress syndrome, which ratio should we be concerned with? |
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Definition
the phosphatidylcholine to sphyingomyeline ratio if it is less than 2 then it is a bad sign and the baby does not have enough surfactant.
Tx: glucocorticoids, artificial surfactant |
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Term
| Patient is B12 deficient and is showing a life threatening acidosis. Patient is unable to process odd chain fatty acids |
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Definition
methylmalonyl aciduria
could also result from defective methylmalonyl CoA reductase |
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Term
| patient shows mental retardation, blindness, muscle weakness and cherry red macula...also shows accumulation of gangliosides |
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Definition
deficiency of hexosiminidase A
Tay sachs disease |
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Term
| 25 year old patient presents with hepatosplenomegaly and mental retardation, also shows osteoporosis of long bones |
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Definition
Def in glucoceribrosidase
This is Gauchers disease
patient will show an accumulation of glucocerebroside |
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Term
| patient presents with kidney failure, reddish purple skin rash, and burning pain in lower extremeity... |
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Definition
Fabry
deficiency: alpha galactosidase
accumulates: globosides
X-linked |
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Term
| patient prsents with hepatosplenomegaly ad mental retardation also shows an accumulation of sphingomelin |
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Definition
Neimann prick
deficiency: sphingomyelinase
(Type A is the most severe) |
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Term
| patient is showing both mental and motor deterioration, is blind, deaf and is loosing myelin |
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Definition
krabbes
deficiency: B galactosidase
accumulation: galactocerebroside |
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Term
| patient is showing progressive paralysis and cognitive deterioration and has an accumulation of sulfatides |
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Definition
metachromatic leukodystrophy
def: aryl sulfataseA |
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Term
| patient presents with a cry like a horse, joint deformity, and granulomas in tissue |
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Definition
Faber
deficiency in: ceraminidase
accumulates: ceramide |
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Term
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Definition
| necessary for cholesterol synthesis |
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Term
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Definition
| necessary for keton body synthesis |
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Term
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Definition
necessary for bile acid synthesis:
activated by thyroid hormones (T3) so people who are hypothyroid are hypercholestrolemic |
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Term
| What is mycophenolic acid used for? |
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Definition
| used during organ transplant to deprive T and B lymphocytes ob bases so that there is no graft rejection. It inhibits IMP dehyrogenase |
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Term
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Definition
| drug that blocks xanthine oxidase, used as a therapeutic for gout patients to stop production of uric acid |
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Term
| What does leflunomide do? |
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Definition
| it inhibits lyphocyte activation and limits inflammation |
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Term
| How does methotrexate work? |
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Definition
| it inhibits DHFR, which helps regenerate THF for syntehsis of thymidine. Inhibition of THF slows DNA synthesis....anticancer drug |
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Term
| Waht does 5-fluouracil do? |
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Definition
| inhibits thymidylate synthase as it is a uracil analog. It is incorporated instead of DUMP and then binds a suicide inhibitor or can be incorporated into RNA. anticancer drug |
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Term
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Definition
| it is a glutamine analogue that can be incorporated anywhere glutamine would be stopping dna synthesis... great anti cancer therapy since glutamine is important for synthesis of all bases. |
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Term
| Which two diseases are associated with purine breakdown? |
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Definition
| SCID(Tx: adenosine deaminase, bone marrow transplant) and Gout (Tx: allopurinol) |
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Term
| what disease is associated with the purine salvage pathway? |
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Definition
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Term
| two examples of inherited hyperuricemia? |
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Definition
1. lesch nyhann
2. von gerke |
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Term
| what is gout where does it usually affect in the body |
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Definition
Too much purine breakdown to uric acid. Which can precipitate out into the blood which are then taken up by macrophages causing them to apoptose causing an inflammatory response.
gout usually affects the small joints (i.e. toe)
Tx: allopurinal to inhibit xanthine oxidase |
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Term
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Definition
| incrase renal excretion of uric acid |
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Term
| patient presents with high uric acid (severe gout), nervous system malfunction and self mutilation, what is it? |
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Definition
lesch nyhan syndrome
usually death before 20 years
X linked
Complete absence of Hypoxanthine guanine phosphoribyl transferase (HGPT) which is necessary for the purine salvage pathway
(partial enzyme deficiency causes gout) |
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Term
| Deficiency of what enzyme results in severe combined immunodeficiency (SCID)? |
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Definition
Adenosine deaminase
which is involved in the breakdown of AMP->IMP. Leads to high levels of dATP in the cell causing a shut down of hte other deoxyribose required for DNA synthesis, this affects immune system as T and B cells must divide rapidly when antigen is present.
Note: dATP work to inhibit ribonucleotide reductase as well. So SCID, an increase in dATP will also slow proliferation of DNA bases in this way as well. |
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Term
| patient presents with growth retardation, megaloblastic anemia, orotic acid crystals in urine. |
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Definition
orotic aciduria which will result from deficiency of UMP synthase complex
Tx: large doses or uridine
Note: drug induced orotic aciduria is caused by deficiency of OMP decarboxylase |
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Term
| How does a vitamin B6 deficiency cause anemia? |
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Definition
| because B6 is ancecessary cofactor for ALAS which is the first step and rate limiting step in heme syntehsis...so if this step is missing there is anemia |
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Term
| how does lead poisoning lead to anemia? |
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Definition
| Ala dehydratase which is the enzyme necesary for hte second step of heme synthesis maintains sulfhydrl groups which make it very susceptable to lead poisoning. thus if soemeons is expose to high levels of lead poisoning then it will interfere with step 2 of heme syntehsis leading to anemia |
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Term
| Patient presents with acute abdominal pain lab tests show accumulation of porphobilinogen and delta ALA. What could be the problem and what enzyme inhibited? |
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Definition
Acute intermittent porphyria
enzyme: PBH deaminase (hydroxymethylbilane synthase)
This disease will remain dormant in a person until something happens to overwork the enzymes.
There is neurovascular pain due to build up of products in CSF and blood.
Specific drugs will cause disease to get worst.
Tx: hematin which is like heme in the but Fe is in ferric state and feeds back to to delta ala synthase to switch off the pathway.
Carb rich meals also help but unsure of mechanism |
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Term
| alcoholic patient presents with cutaneous photosensitivity , skin rashes and blisters. In fluorescent light there urine turns pink. What could this be? |
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Definition
Porphyria cutanea tarda
enzyme: uroporphyrinogen decarboxylase
accumulation of: uroporphyrinogen
Tx: avoid sunlight so as not to have oxidation of built of uroporphyrinogen
Abstain from alcohol because alcohol is detoxified using the p450 system and will cause an increase in enzyme activity.
Phlebotomy to remove blood and reduce the amount of built up porphorin. |
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Term
| if patient is suspected as having a liver disease what is tested? problems with bile duct? |
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Definition
liver=high AST and ALT
bile duct= alkaline phosphatase and gamma GT |
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Term
| describe unconjugated hyperbilirubinemia. and explain how it relates to hemolytic disease of the newborn. |
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Definition
Very Dangerous!
Caused by: hemolysis the excess breakdown of RBCs/hemolytic anemia.
enzyme deficiency: UDP glucoronyl transferase which is responsible for conjugating bilirbuen in the liver so that it can be excreted with the bile into the intestine.
In the most extreme case, there is kernicterus, which means that the amount of unconjugated billiruben exceeds the amount of albumin available so there deposits of the billirubin in nervous tissue which causes massive mental retardation in the newborn. |
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Term
| why is conjugated billirubenemia not so dangerous? |
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Definition
Because it is water soluble so it will be excreted, since it was conjugated.
It is caused by: gall bladder stones or cancer of the pancreas.
Tx: UV light which works to break down billiruben under the skin and then it can be excreted with water. |
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Term
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Definition
unconjugated billiruben is slightly raised.
can present at any time in life (usually in second decade)
Needs an event to bring it on i.e. hepatitis
seen when plasma billiruben levels have not returned back to to normal after a minor illness
Although harmless it needs to be distinguished from hemolysis or hepatitis. Soshould test for transaminases, if their levels are normal then u know its Gilbert syndrome
cause: decreased expression of udp glucoronyl transferase |
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Term
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Definition
very dangerous!
deficiency: UDP glucornyl transferase
presents in babies at birth
Type1: complete absence, autosomal recessive, not treatable
Type 2: autosomal dominant but treatable with phenobarbitone. Should normalize so wont have to be administered through life
major problem if kernicterus....if not treated quickly enough |
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Term
| Patient presents with raised plasma and urine conjugated bilirubin levels. ALP levels are normal and liver shows to be a dark brown pigmented appearance |
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Definition
dubin johnson syndrome (harmless)
-Rotor syndrome is hte same but without pigmented liver |
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Term
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Definition
Alt/AST normal
high unconjugated billirubin
high conjugated billirubin
high urobilinogen in urine
all pathways working fine just overload usually a result of hemolysis |
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Term
|
Definition
increased ALT and AST (early)
increased gamma Gt and ALP (later)
increased conjugated billirubin
increased urobillinogin in urine
dying hepatocytes |
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Term
| Post hepatic obstructive jaundice Dx |
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Definition
increased gamma GT and ALP
increased confjugated billirubin in urine
no urobilinogen because none made it to the intesnstine since there is an obstruction of getting conjugated billirubin out.
Transaminases are normal cuz nothing is wrong with the liver
Usually a result of obstruction of the bile duct. |
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Term
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Definition
CTG repeat (trinucleotide repeat disease)
Mutation in 3' untranslated region of DMPK gene
4-40 repeats is normal
shows step wide expansion
50-100 is mild= cataract
100-1000= congenital= cataract, myotonia grip muscle weakness
>1200 cngenital= mental retardation, early death, hypotonia respiratory ineficiency
Dx: clinical eye exam creatine kinase, EMG |
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Term
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Definition
Loss of function mutation (trinucleotide repeat)
X linked disorder
mutation in 5'promotor region of FMR1 gene
Maternal bias but premutation from the father can reduce the size of the repeats.
premutation (59>200) males and females have normal intellect with premutation but are at risk of POF (females) males (FXTAS)
Dx: PCR or souther blot anaylsis using EAG1 and ECOR1 |
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Term
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Definition
Trinucleotide repeat, gain of function mutation in Exon 1 of huntingtins gene due to expanded polyglutamine tract
35-39= reduce penetrance
>40 = disease
>60=juvenile onset
Dx: PCR |
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Term
| what two reactions in the human body require B12? |
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Definition
1. methionine synthase
2. methylmalonyl CoA mutase ( for odd chain fatty acid metabolism) |
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