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47 Cards in this Set
- Front
- Back
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There are many different inherited biochemical disorders
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These disorders typically involve deficiencies of enzyme production or buildup of toxic metabolites or both
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usually what is the inheritance?
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AR
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What are some early signs of a metabolic disorder?
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metabolic acidosis
poor feeding vomiting lethargy convulsion |
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they often end up with
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MR
organomegaly body odors episodic decompensations |
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common components of the newborn screen
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PKU
hypothyroidism hemoglobinopathies galactosemia sickle cell CF |
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What is the presentation for most disorders of fatty acid oxidation?
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hypoglycemia
even sudden death |
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tx of these diseases often involves dietary mods and increasing availability of enzyme of gene-related treatment options
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ok
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What is PKU?
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usually due to deficiency of phenylalanine hydroxylase and inability to convert Phe to tyrosine
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What is the other possible cause for PKU?
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tetrahydrobiopterin deficiency (cofactor for Phe OHase)
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What is the pathophys of PKU?
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phenylalanine and its toxic metabolites build up and Tyr becomes an essential amino acid
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Severe MR can develop within 1 year of age
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they also show hypopigmentation due to low tyrosine and low melanin production with tyrosinase inhibition
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They also show eczema and
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mousy body odor
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tx for PKU
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no phenylalanine in the diet and supplement tyrosine
these children can even have normal IQ if Phe is limited |
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What is a common chemical to contain PKU
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aspartame
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What are some possible enzyme deficiencies to result in homocystinuria?
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cystathionine synthase deficiency
methyltetrahydrofolate reductase deficiency |
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so it depends on which enzyme is deficient that determines what to supplement
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if CH3-THF reductase is deficient then you want to give B12
B6 for cystathionine synthase otherwise homocystine builds up in the tissues and causes all kinds of problems |
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What is homocystinuria similar to in presentation?
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Marfan syndrome- shares a lot of lens and skeletal defects with Marfan
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So what are the major effects of PKU
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Marfanoid habitus
cataracts, lens subluxations, retinal detachments ectopia lentis where the iris quivers with lens dislocation fair skin with possible malar flush |
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They categorize the different forms as pyridoxine-sensitive or resistant
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the pyridoxine resistant form requires methionine restriction
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What is the defect for MSUD?
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defect of branched chain amino acid metabolism.
deficiency of branched chain ketoacid dehydrogenase |
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What are the branched chain amino acids that build up?
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leucine, isoleucine, valine
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The only symptom that really tells you anything is...
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the burnt sugar smel to the urine- otherwise it's things like alternating between flaccidity and convulsions, hypoglycemia etc.
the presentation is extremely variable because so many parts of the enzyme can be affected |
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tx for MSUD
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limit branched chain aa's in the diet
in an acidotic crisis= dialysis |
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What aa is usually at the highest level in MSUD?
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leucine
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What is the defect of Hartnup disease?
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defective transport of neutral amino acids in the intestine and renal tubules
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What is the big problem that results in Hartnup disease manifstations
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results in trypthophan deficiency
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What are the plasma levels of amino acids in Hartnup disease?
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normal- it's a defect primarily of the renal tubules reabsorbing them so it shows high levels in the urine instead
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tx for Hartnup?
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supplement NAD and protein in the diet
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How do you differentiate Hartnup from Fanconi syndrome?
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Hartnup shows normal levels of charged amino acids like arginine, hydroxyproline, and proline
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What are the neutral amino acids you expect to see in the urine of a Hartnup patient?
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alanine
serine threonine valine leucine isoleucine Phe tyrosine tryptophan histidine |
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What is the most common lysosomal storage disease?
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Gaucher's disease
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What is the enzyme defect in Gaucher? What builds up as a result?
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B-glucosidase deficiency
causes accumulation of glucocerebroside |
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What bone marrow effect do you see?
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you see "crinkled paper" cytoplasm. This disease results in pancytopenia
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tx for Gaucher?
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enzyme replacement therapy of glucosidase
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What is Niemann Pick disease?
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deficiency of sphingomyelinase causes accumulation of cholesterol and sphingomyelin all over the nervous system
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buzzword physical exam finding for Niemann Pick
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cherry red macular spot but with a clear cornea
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Because there is cholesterol accumulation in the cells, what do you see on bone marrow aspirates?
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foam cells
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otherwise the signs and symptoms of Niemann pick are pretty non-specific
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jaundice
hsmegaly |
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What is Farber disease?
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deficiency of ceramidase
causes ceramide to build up in organs, joints, and lymph nodes causes severe MR and other crap |
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What enzyme defect for Fabry disease?
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deficiency of ceramide trihexosidase or alpha-galactosidase A
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What are the signs of Fabry disease?
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angiokeratomas- which are dark red macules that occur in clusters bilterally around the navel and buttocks
neuropathic limb pain corneal deposits |
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What is Tay sachs?
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deficiency of hexosaminidase A
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What accumulates in Tay Sachs?
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GM2 ganglioside
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Sandhoff disease is basically the same as Tay Sachs
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both show a cherry red spot
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What population for Tay Sachs?
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ashkenazi Jews
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What is the only LSD that is X linked recessive?
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Hunter syndrome
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What is the enzyme defect of Hunter syndrome?
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iduronate 2 sulfatase
Whatever. |
