Create
Learn
Share

Biochemistry Disorders

rename
bananas's version from 2015-07-19 16:33

Lysosomal storage diseases

DiseaseInheritanceEnzymeMetaboliteClinical Presentation
Fabry DiseaseX-Linked Recessivealpha galactosidaseceramide trihexosideangiokeratomas, cardiac and renal involvement, and painful neuropathy
Gaucher Diseaseautosomal recessiveB-glucocerebrosidesglucocerebrosideGaucher cells (macrophages that look like crumpled tissue paper), hepatosplenomegaly, pancytopenia, severe bone and joint pain
Hurler syndromeautosomal recessivealpha-L-iduronidasedermatan and heparan sulfategargoylism, corneal clouding, hepatosplenomegaly, developmental delay
Niemann-Pick diseaseautosomal recessivesphinomyelinasesphinomyelinhepatosplenomegaly, cherry-red spot in macula, foam cells, progressive neurodegeneration
Tay Sachs diseaseautosomal recessiveB-hexosaminidase AGM2 gangliosidecherry-red spot in macula, progressive neurodegeneration,NO hepatosplenomegaly
Krabbe diseaseautosomal recessivegalacto-cerebrosidasegalactosyl-sphingosine and galactocerebrosideprogressive neurodegeneration and optic atrophy
metachromatic leuokdystrophyautosomal recessivearylsulfatase Acerebroside sulfatemuscle wasting, dementia, ataxia
Hunter syndromeautosomal recessiveiduronate sulfateheparan sulfate, dermatan sulfatemild Hurler plus aggressive behavior, no corneal clouding
memorize

Hereditary Defects in Sugar Metabolism

EnzymeEnzymeAccumulatesClinical Presentation
Galactokinase deficiencyGalactokinaseGalacitol accumulatesAsymptomatic
Infantile cataracts
Predisposed to gestational diabetes
Classic GalactosemiaBad Galactose-1-phosphate uridyltransferase- Galactose 1-phosphate (toxic)
- Galactose (blood, urine)
- Galacitol (sugar alcohol)
Failure to thrive
Jaundice and hepatomegaly
Infantile cataracts
Intellectual disability
Essential FructosuriaNo Fructokinase: No build up because Hexokinase converts to F6P for glycolysisFructosuriaAsymptomatic
Hereditary fructose intoleranceNo Aldolase B- Fructose
- Fructose-1-phosphate
Symptoms with fruit, juice or honey
Hypoglycemia
Jaundice, cirrhosis, toxic liver damage
Renal disease
memorize

Glycogen Storage Diseases (all autosomal recessive)

DiseaseaEnzymeClinical Presentation
Von Gierke (I)Glucose 6-phosphatase
(liver and kidney)
Liver cannot release stored glucose (increased glycogen in liver) leads to hepatomegaly.
- Lactic acidosis
- Severe fasting hypoglycemia
- Hepatic steatosis is a cardinal sign!
Pompe (II)alpha-1,4-glucosidase
(lysosomes)
Buildup of glycogen in cardiac muscles.
- Electron dense granules inside lysosomes
- Restrictive cardiomyopathy is typical cause of death by age 2.
Cori (III)Debranching enzyme 1,6 glucosidase
- in muscle and liver
- Weakness and hypotonia
- Cytosolic accumulation of glycogen with abnormally short outer chains
McArdle's (V)Glycogen phosphorylase
- in skeletal muscle
Exercise intolerance
- muscle cramping
- fatigue
- myoglobinura >> rhabdo
memorize

Catecholamine synthesis/ tyrosine catabolism

Question Answer
phenylalanine to tyrosinephenyalanine hydroxylase w/BH4
tyrosine to DOPAtyrosine hydroxylase with B4
DOPA to dopamineDOPA decarboxylase with B6
Dopamine to NEvitamin C
NE to EPiphenyletholamine-N-methyltransferase and SAM
memorize

Amino acid deficiencies

DiseaseEnzymeAccumulateClinical Presentation
PKUPhenyalanine hydroxylase
Cofactor BH4
Phenylalanine
Phenylketones (urine)
Musty smell
Intellectual disability
Fair skin
Eczema
Seizures
↓ phenylalanine
↑ tyrosine
AlkaptonuriaHomogenestic acid oxidaseHomonogestic acidBlack urine
AlbinismTyrosinase
- Can also be caused by failure of neural crest migration
(Tyrosine)- increased risk of skin cancer
Homocystinuria1. Cystathionine synthase (+B6)
2. Homocysteine methyltransferase (+B12)
Homocysteine
Methionine
+methyltransferase
Intellectual disability
Osteoporosis
Marfenoid: kyphosis, lens subluxation
Thrombosis and atherosclerosis
CystinuriaPCT renal defect preventing reabsorptionCOLA
Cysteine
Ornithine
Lysine
Arginine
Cystine stones: staghorn calculi- urinary alkalinization
- citrate
- hydration
Maple syrup urine diseaseAlpha ketoacid dehydrogenaseBranched aa's:
Valine
Isoleucine
Leucine
Burnt sugar/syrup smelling urine
CNS defect
Intellectual disability
Thiamine
↓ isoleucine, leucine and valine.
HartnupAmino acid clearance
- Niacin deficiency
TryptophanPellagra:
- Dementia
- Dermatitis
- Diarrhea
OTC deficiencyOrnithine transcarbamylaseOrotic acid
- blood and urine
Hyperammoniemia.
- Encephalopathy

No megaloblastic anemia (vs orotic aciduria)
Orotic aciduriaUMP synthaseOrotic acidMegaloblastic anemia
- refractory to Folate and B12

No hyperammoniemia.
Uridine monophosphate
memorize

Fatties

ApolipoproteinWhat it doSymptoms of defect
ApoC-II or Lipoprotein lipase deficiencyChylomicrons, TG, CholesterolCreamy plasma
Pancreatitis, Hepatosplenomegaly, Pruritic xanthomas
LDL receptorLDL, CholesterolAD MI before 20, tendon xanthoma, corneal arcus
ApoAVToo much! VLDL, TGHypertriglyceridemia>> Acute pancreatitis
ApoE: Remnant uptakeChylomicron and VLDLPremature CAD and Palmar xanthomas!
ApoA-1: Activate LCAT for chylomicron and HDLChylomicron, HDL
ApoC II: Lipoprotein lipase cofactorChylomicron, VLDL, HDL
ApoB-48: Chylomicron secretionChylomicron
ApoB-100: Bind LDL receptorVLDL, IDL, LDL
memorize