Clinical Flashcards
What enzyme is missing in galactosemia? What are some symptoms? How do you treat it?
Note: inherited AR
UDP-glucose -> galactose-1-P uridyltransferase; hepatomegaly, cataracts, CNS damage; removal of galactose from diet (lactose)
An indirect problem from fructose metabolism is gout. Why?
ADP and AMP is broken down, which leads to uric acid buildup
What disease?
nausea/vomiting after eating foods w/ fructose, hypoglycemia, potential liver damage, AR
aldolase B deficiency (fructose intolerance)
What disease?
relatively benign, fructose eliminated in urine w/o metabolism
fructokinase def. (essential fructosuria)
What are the 2 vitamin deficiencies?
- muscle weakness and mental confusion
- dry, cracked lips and mild dermtitis
- B1 - beriberi (thiamine pyrophosphate)
2. FAD (riboflavin/B2)
What is the disease, and what enzyme is deficient?
glycogen accumulates in liver/renal tubule cells, hypoglycemia, lactic acid, ketosis, and hyperlipemia
Type Ia - Von Gierke; glucose-6-phosphatase
What is the disease, and what enzyme is deficient?
accumulation of glycogen in lysosomes; child: muscle hypotonia and death from heart by 2; adult: muscle dystrophy
Type II - Pompe; lysosome α1->4 and α1->6 glucosidase
What is the disease, and what enzyme is deficient?
hypoglycemia, hepatomegaly, accumulation of a-dextrin, weak muscles
Type IIIa-Cori; liver and muscle debranching enzyme
What is the disease, and what enzyme is deficient?
hepatosplenomegaly, accumulation of branched sugar, death from heart or liver by 5 years of age
Type IV-Andersen; branching enzyme
What is the disease, and what enzyme is deficient?
poor exercise tolerance from low blood lactate, high muscle glycogen
Type V-McArdle; muscle phosphorylase
What is the disease, and what enzyme is deficient?
hepatomegaly, accumulation of glycogen in liver, mild hypoglycemia, “good”
Type VI-Hers; liver phosphorylase
What is the disease, and what enzyme is deficient?
XR; found in African Am., Mediterranean, and Asian; under stress, drug treatment or ingestion of fava beans leads to hemolytic anemia because there’s decreased NADPH
glucose-6-P dehydrogenase deficiency
What is the group of diseases?
absent peroxisomes in hepatocytes and fibroblasts, accumulation of VLC FA’s, phytanic acid, and bile acid intermediates/plasmalogen def, mutations in PEX 2, 5, 6, and/or 12
zellwegger spectrum disorders
What is the disease?
craniofacial, neuro, and ocular problems, hypotonia, epileptic seizures, severe psychomotor retardation, micropolygyria (impaired neuronal migration and severe demyelination); patients die by end of year 1
Zellwegger Syndrome
What is the disease?
milder ZS symptoms w/ adrenal atrophy
neonatal adrenoleukodystrophy
What is the disease?
no neonatal abnormalities and only mild dysmorphia; mental retardation, retinitis pigmentosa, neurosensory deafness, growth retardation
infantile refsum’s disease
What is the disease?
X-linked, postlingual progressive sensorineural deafness, dystonia, spasticity, dysphagia, mental deterioration, paranoia, and cortical blindness
human deafness dystonia syndrome aka Mohr-Tranebjaerg
What is the disease?
X-linked, infantile cardiomyopathy, abnormal cardiolipin composition, skeletal myopathy, neutropenia, and growth retardation; could be defect in phospholipid acyltransferase aka tafazzin that normally remodels cardiolipin by linoleate transfer
Barth syndrome
What is the disease, and what is the DNA mutation?
progressive myoclonic epilepsy, mito. myopathy w/ ragged red fibers, and slowly progressive dementia; late childhood to adult
MERRF; point mutation in tRNA-Lysine
What 2 drugs block both PLA2 and cyclooxygenase?
What other 2 drugs also block cyclooxygenase?
cortisone and prednisone
aspirin and ibuprofen
Carnitine def. is the decreased ability to use LCFA as fuel, which means you get an accumulation of toxic amounts of free FA’s. What are the 5 causes of this deficiency?
- liver dis. (where carnitine is made)
- malnutrition or vegetarian diet (no meat)
- increased requirement - burns or pregnancy
- hemodialysis - made in kidneys; you’re on this, you have bad kidneys. 5. congenital def.
In ability to use LCFA as fuel, as in carnitine def., impairs the body the ability to do what?
make glucose during a fast –> hypoglycemia, coma, and death
sustain exercise
What is the disease, and what is the deficient enzyme?
retinitis pigmentosa, progressive peripheral neuropathy, skeletal malformations, severe motor weakness, peroxisomes can’t attack microbes
Refsum disease; peroxisomal enzyme responsible for 1 of the starting steps in oxidation of phytanic acid
Absence of insulin, as in diabetic ketosis, can cause what 2 major biochemical problems? What does the liver produce in diabetic ketosis?
liver can’t provide oxaloacetate and insulin normally decreases FA metabolism
large amount of ketone bodies
What up regulates the transcription of PEPCK in adipose tissue? What down regulates it?
What up regulates it in the liver?
thiazolidinediones (pill that controls diabetes); glucocorticoids (goes up during stress)
glucocorticoids
What disease has an accumulation of ceramide?
Farber’s disease
What is the disease?
failure to degrade gangliosides due to lack of hexoamininidase A, buildup of gangliosides in nervous system –> disability and death
Tay-Sachs
What is the disease? - accumulation of sphingomyelin due to defect in sphingomyelinase; three types:
A: dis. begins during infancy, enlarged liver, and spleen, failure to thrive, progressive detrioration of Nervous System
B: less severe C: not diagnosed until adulthood
Niemann-Pick disease
What is the disease?
macrophages become filled w/ undigested glucocerebroside, spleen and liver enlarge, fatigue, bleeding problems, fragile bones
Gaucher’s disease
What groups of people may have lactose deficiency? What other group of people have decreased lactase?
infants, Mediterranean, African black, Native American, Mexican American, and Asian
older adults
What cycle is affected with any of the following deficiencies? What does a defect in this cycle cause?
argininosuccinate lyase def. (treat w/ arginine), carbamoyl phosphate synthetase I def., ornithine transcaramoylase def., argininosuccinate synthase def.
urea cycle
hyperammonemia
What is the disease?
def. of the dehydrogenase enz. that helps to breakdown isoleucine, leucine, and valine; these accumulate in blood and urine; distinct odor; mental and physical deficits unless diet is restricted
maple syrup urine disease
I Love Vermont maple syrup.
What is the disease?
def. of homogentisate-1,2-dioxygenase, homogentisate accumulates and colors when exposed to air, toxic metabolite produced by oxidation that must be avoided: benzoquinone acetic acid, treat w/ restricting Phe and Tyr in diet, take large doses of ascorbic acid
alcaptonuria
What is the disease?
def. of phenylalanine hydroxylase, phenylalanine accumulates, mental retardation if untreated, treat by Phe-restricted diet
phenylketonuria (PKU)
What is the disease?
def. of arginosuccinate lyase; lethargy, seizures, decreased muscle tension
citrullinema
What is the disease?
various enz. def., weakness, self-mutilation, liver damage, mental retardation
tyrosinemia
What is the disease?
def. of tyrosinase, absence of pigmentation
albinism
What is the disease?
def. of cystathionine β-synthase, scoliosis, muscle weakness, mental retardation, thin blond hair
homocystinuria
What is the disease?
def. of α-aminoadipic semialdehyde dehydrogenase, seizures, mental retardation, lack of muscle tone, ataxia
hyperlysinemia
What do high levels of homocysteine put you at an increased risk for?
High levels indicate what enzyme is lacking?
How is homocysteine excess treated?
CVD
cystathionine synthase
folate and vitamin B6
What is the porphyria?
uroporphyrinogen III cosynthase defect, photosensitive
congenital erythropoietic
What is the porphyria?
defect of ferrochelatase, photosensitive
erythropoietic protoporphyria
What is the porphyria?
ALA dehydratase def. and photosensitive
ALA dehydratase def.
What is the porphyria?
porphobilonogen deaminase defect and neurovisceral issues
acute intermittent porphyria
What is the porphyria?
defect in coproporphyrinogen oxidase, neurovisceral, and some photosensitivity
hereditary coproporphyria
What is the porphyria?
defect of protoporphyrinogen oxidase, neurovisceral, photosensitive
variegate porphyria
What is the porphyria?
defect in uroporphyrinogen decarboxylase, photosensitive
porphyria cutanea tarda
What two enzymes are subject to lead poisoning? What will this lead to a buildup in?
δ ALA dehydratase and ferrochelatase; lead to buildup of δ-ALA and coproporphyrin in serum and urine
ALA dehydratase def. and acute intermittent porphyria lead to a buildup of what? Patients with either will have abdominal pain and psychiatric disturbances. How do you treat them?
ALA and porphobilonogen
P-450 metabolized drugs
What occurs when bilirubin production is greater than excretion? Where is the excess deposited? What color does a person with this condition appear to be?
jaundice; skin and sclera; yellow
What can cause jaundice?
sickle cell anemia, obstruction of bile duct (backed up bilirubin), and liver damage
