what trinucleotide repeat codes for FMR1 gene
CGG (fragile X syndrome) (CGG) Chin (protruding) Giant Gonads
Fragile X syndrome inheritance is ?
X linked dominant inheritance
in Fraile X syndrome. explain what a trinucleotide repeat dose?
CGG repeat in FMR1 gene --> HYPERmethylation --> decrease expression.
pt presents with post-pubertal macroorchidism (giant balls) long face w/ large jaw, large everted ears, autism predisposed to mitral vale porlapse
Fragile X syndrome
most common cause of INHERITED intellectual disability and autism?
Fragile X syndrome. its the 2nd most common cause of GENETICALLY associated mental deficiency (after DOWNS)
Caudate has dec Ach and GABA
Myotonic dystrophy trinucleotide repeat?
Cataracts, Toupee (early balding in men), Gonadal atrophy
CGG trinucleotide repeat?
Fragile X syndrome
GAA trinucleotide repeat
6yo w/ persistent facial ulcer for past 2 months. extreme sensitivity to sunlight and has developed freckle on sun exposed areas since infancy. PE; skin is dry and rough and erythematous macules. there is an ulcerated plaque on face. biopsy (Squamous cell carcinoma) hes diagnosed w/ xeroderma pigmentosum. what enzyme is most likely causing this condition?
what disease has a deficiency in endonucleases which prevents repair of pyrimidine dimers that are formed as a result of UV light exposure? and what type of DNA repair is this described above
Nucleotide excision repair.
what phase of the cell cycle dose nucleotide excision repair occur?
A 4-year-old male presents to his pediatrician for a routine physical examination. Physical examination reveals the presence of hyperpigmented lesions that vary in color from light brown to dark brown, axillary freckling, and Lisch nodules. The most likely gene involved is A. HFE B. NF1 a tumor suppressor gene C. Nf1 oncogene D NF2 tumor suppressor E. NF2 oncogene
B. NF1 gene located on chromosome 17 is a tumor-suppressor. Inactivation results in Neurofibromatosis type-1. NF2 is also TS
HFE gene are located chromosome 6 results in ______________. autosomal recessive. leads to iron deposits in liver ,pancreas, heat, skin. iron overload due to accelerated rate of iron absorption in intestine.
A 23-year-old female presents with a sore throat and a scaling rash around her mouth. Physical examination reveals hyperemia of pharyngeal mucous membranes, edema of mucous membranes, angular cheilitis, and an oily scaling nasolabial rash. The most appropriate initial pharmacological treatment is?
A deficiency in riboflavin can result in angular stomatitis, glossitis, and seborrheic dermatitis. A normocytic-normochromic anemia may also be appreciated on a complete blood count.
a pt diagnosed with anorexia nervosa or malabsorptive syndrome (celiac sprue) presents with
Sorethroat, hyperemia of pharyngeal mucous membranes, edema of mucous membranes, chelitis, stomatitis, ,glossitis, and seborreheic dermatitis.
what vit is def?
what is the function of Rb tumor suppressor?
Rb, a tumor suppressor protein which holds DNA within G1 until it is ready for division.
Retinoblastoma protein is a tumor suppressor protein that prevents excessive cell growth. It holds the cell cycle during the G1 phase. The tumor, called retinoblastoma, forms when both alleles of the protein are inactivated by phosphorylation.
A 16-year-old male presents to his primary care physician for an annual check-up. Physical examination reveals milky white skin and white hair with blue and translucent irises. Which of the following enzymes is most likely deficient in this patient?
A. acetaldehyde dehydrogenase
B. tryptophan hydroxylase.
D. tyrosine kinase
congenital albinism is often due to a deficiency in tyrosinase, the enzyme responsible for converting tyrosine to melanin. Hereditary forms can be autosomal dominant or recessive. Albinism can also result from altered neural crest cell migration. Patients present with a varying degree of skin and hair hypopigmentation, translucent irises, and ocular complications. They are also at increased risk for skin cancer.
A 6-month-old female with a skin rash is presented to her pediatrician. The child has also been experiencing bouts of diarrhea. The parents have also noted that the child's skin typically reddens after exposure to sunlight. Upon physical examination, the pediatrician notes dry, scaly, well-marginated eruptions of the skin of the forehead, cheeks, and back of the hands. After laboratory testing, a deficiency in the absorption of an essential amino acid is suspected to be involved. The amino acid in question is most likely and what disease
defective GI absorption and renal reabsorption of the essential amino acid tryptophan, resulting in deficiency of vitamin B3.
A 3-year-old female presents with frequent paroxysms of inappropriate laughter and hyperactivity. Physical examination reveals maxillary hypoplasia, deep-set eyes, and a large mouth with tongue protrusion. The gait is jerky and puppet-like. Osteopathic Cranial Manipulative Medicine is initiated, which the mother associates with a subjective improvement of 50% in her daughter's ability to sleep as well the hyperactive periods. The most likely genetic cause the patient's underlying disorder is
A. maternal uniparental disomy of chromo 15
B. Maternally-derived microdeletion on chromo 15
partial deletion of short arm of chromo 5
paternally-derived microdeletion on chromo 15
maternally derived microdeletion on chromo 15
A 28-year-old professional bodybuilder presents with alopecia, muscle pain, and an erythematous perioral macular rash. He is currently being treated for depression with sertraline. His diet consists of a massive amount of protein and raw eggs. These signs and symptoms are most consistent with a deficiency of
A deficiency in biotin can occur in patients who consume a large amount of raw eggs due to the biotin binding enzyme avidin. Biotin deficiency can result in dermatitis, alopecia, enteritis, and depression.
An underweight, 35-year-old known alcoholic female presents to the neighborhood clinic with complaints of headaches, diarrhea, memory loss, and a rash. Physical examination shows erythematous dry plaques on her arms. She states that these plaques are worse when she is in the sunlight. Because of her history, a nutrient deficiency is suspected. It is most likely that this deficiency is
A. Foilic acid
Niacin deficiency results in pellagra which clinically presents as the “4 Ds”. The 4 Ds are dermatitis, diarrhea, dementia, and death.
where is Rrna made?
Vit A functions are?
consistuent of visual pigments (retinal) (think retinol is vitamin A, so think retin-A)
differentiation of epithelial cells into specialized tissues (pancreatic cells, mucus- secreting cells
vit A used to treat?
(APL) acute promyelocytic leukemia.
Oral isotretinoin to treat severe cystic acne.
use all-trans retinoic acid to treat APL
def in VIT A
night blindness (nyctalopia)
dry scaling skin (xerosis cutis)
corneal degeneration (keratomalaxia)
Bitot spots on conjunctiva; immunosuppression
in thiamine pyrophosphate (TPP) a cofactor for 4 dehydrogenase enzyme rxns. what are they?
a-ketoglutarate dehydrogenase (dehydrogenase TCA cycle)
Transketolase (HMP shunt)
Pyruvate dehydrogenase. (links glycolysis to TCA cycle)
Branched-chain ketoacid dehydrogenase.
what vitamin is involved in Beri Beri
Dry beri beri: polyneuritis, symmetrical muscle wasting.
wet beri beri: high output cardiac failure (dilated cardiomyopathy) edema, tachycardia.
a pt presents with polyneuritis, symmetrical muscle wasting. you make the diagnosis of dry beri beri what vit are they def in?
Vit B2 riboflavin is a component of ____________ and _______
which are used in redox rxns.
example: succinate dehydrogenase rxn in the TCA cycle
flavins FAD and FMN
(" FAD and FMN are derived from riboFlavin)
(B2 = 2 atp)
the 2Cs of B2 deficiency are?
Cheilosis (inflammation of lips, scaling, and fissures at the corners of the mouth(
a pt complains of burning feet (paresthesias)
on PE you see dermatitis, enteritis, alpecia, adrenal insufficiency
what vit are they deficient in and what component is it essential for
B5 pantothenic acid
essential component of coenzyme A
a pt develops facial flushing. this patients symptom is most likely do to Excess of _________ vitamin and the mechanism of this flushing is due to?
what can this patient take with this vitamin to prevents this rxn
vit B3 niacin excess causes facial flushing via (induced by prostaglandin, NOT histamine)
in glycolysis what is the rate limmint step? what is the enzyme
Fructose-6-P -------(Phosphofructokinase-1)---------> FRUCTOSE 1-6-bp
What are the 3 places where glycolysis is regulated?
1. hexokinase / Glucokinase
glucose --> G6P
. F6P --> F-1-6-P
3. Pyruvate kinase
PEP ---> pyruvate
in glycolysis for the enzymes PFK1 and Pyruvate kinase. what inhibits or activates these enzymes?
activators: AMP, fructose-2.6-bisphophate
inhibitors: ATP, citrate
atp and alanine
Vitamin B5 is essential for what cofactor?
CoA (a cofactor for acyl transfers)
fatty acid synthase
vit B6 (Pyridoxine) is a cofactor used in? (main answer, since it has multiple)
Transamination (ALT, AST)
vit B7 (BIOTIN) is a cofactor for?
carboxylation enzymes (add a 2 carbon group)
pyruvate carboxylase: pyruvate (3C) --> oxaloacetate
what vitamin is used in a disease that you cant reduce Fe3+ to Fe2+
Vit C (ascorbic acid)
ancillary tx for methemoglobinemia
what vitamin is required for HEME synthesis?
Vit B6 pyridoxine
succinyl coa + glycine ---> ALA
your pt has been on nitroprusside for tx of hypertensive emergencies for a 3 days. what are they are risk of developing?
how would you treat this devlopment
cyanide poisoining bc (nitroprusside contains 5 cyanide grps per molecule, toxic with prolonged infusions)
TX:NITRITES (amyl nitrite)
converts Fe2+ --> Fe3+ in Hgb (methemoglobin)
Fe3+ in HgB binds the cyanide, thus protecting the mtichondria. thus this allows them to start oxidative phosphorylation again until the cyanide is washed out of the system.
this prevents lactic acidosis
a pt is deficiency/defect in fructokinase whats the diagnosis
its benign! only abnormality will be fructose in urine.
if a patient has a deficiency in aldolase B what substance/substrate will be elevated?
fructose 1- phosphate
F-6-P accumulates causing a dec in available phosphate,--> dec ATP --> inhibition of glycogenolysis and gluconeogenesis
bc aldolase B enzyme catalyzes F-1-P into dihydroxyacetone-phosphate and glyceraldehyde.
diagnosis fructose intolerance.
a baby just weaned from breast milk. mom is bringing her baby in because of having a seizure yesterday (hypoglycemia) mom says she gave her baby some fruit for lunch with juice and honey 30 minutes ago before walking into the office. on physical exam the baby has an enlarged liver (hepatomegaly) jaundice, vomiting. what is wrong with the baby, and what is the best treatment?
hereditary fructose intolerance
due to a def in aldolase B.
treatment. dec intake of both fructose and sucrose (glucose + fructose) and sorbitol..
why should patients with hereditary fructose intolerance avoid sorbitol?
bc sorbitol can be converted to fructose via sorbitol dehydrogenase.
glucose ------ALDOSE REDUCTASE --> sorbitol ----- sorbiotol dehydrogenase --> fructose.
what enzyme converts glucose into sorbitol
accumulation of sorbitol in tissues is related to complications of hyperglycemia and diabetes.
in metabolism of Galactose. what are the two enzymes used to eventually form glucose-1-P
glactose ----(___________)---> Glactose-1-P -----)____________) ---> Glucose-1-P
a 3 day old neonate after breast feeding. develops jaundice, hepatomegaly, and intellectual disabiltiy. you diagnose this child with classic galactosemia.
1. what enzyme is abscence causing this?
2. if this ineonate isnt treated what will they most likely develep?
1. galactose-1-phosphate URIDYLTRANSFERASE.
2. infantile cataracts.
exclude galactose and lactose (glactose+ glucose) from diet.
a pt with classic galactosemia. develops infantile catacts. what is the cause of the cataracts
build up of galactitol in the lens
a young child presents with vision problems. after getting labs the child has galactose in blood (galactosemia) and urine (galactosuria) what is this this disease called?
a child with galactokinase deficiency will most likely develop what if left untreated
this results in excess NH3, which depletes alpha- ketoglutarate, leading to inhibition of the TCA cycle.
pts will presents with CNS symptoms: tremors (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision.
can be acquired (liver disease) or hereditary (urea cycle enzyme def)
whats the treatment of hyperammonemia
limit protein in diet
others meds givien to dec ammonia levels
lactulose to acidify the GI tract and trap NH4+ for excretion
abx( rifaximin) to dec colonic ammoniagenic bacteria.
and for pts with urea cycle enzyme def: benzoate, phenylacetate, or phenylbutyrate.
most common urea cycle disorder
what enzyme is defective
inc carbamoyl phosphate
inc orotic acid (derived from carbamoyl phosphate?
A. ornithine transcarbamylase def
B. orotic aciduria (disorder of pyrimidine syntnhesis.
orotic aciduria does not have inc in ammonia bc not a urea cycle problem.
inc orotic acid in bloood and urine,
symptoms of hyper ammonemia.
no megaloblastic anemai (vs orotic aciduria)
ornithine transcarbamylase def
this disease results from cellular inability to add mannose-6-phospate to lysosomal proteins
I cell disease.
babies present with musty body/urine odor, seizures, fairr skin, eczema, growth retardation , intellectual diasability. Also can see blue eyes, pale skin.
what enzyme is responsible for this? and what lab valuesdo you expect to see?
def in phenylalanine hydroxylase or (dec in cofactor (BH4) tetrahydrobiopterin = malignant PKU)
labs: inc phenylalanine and dec tyrosine.
a child was given juice with added aspartame (artificial sweetener) she had a seizure and her urine is musty odor whats the cause?
child with pale skin, blond hair, blue eyes, came in complaining of getting sunburns easy. she has a history of oculocutaneous albinism type 1. what enzyme is she deficient in type1?
and what syndrome is type 2 seen in?
def in tyrosinase.
type 2 seen in Chediakk-HIgashi syndrome.
tyrosine transporter defect
cysteine residues are attached to their appropriate tRNAs by the enzyme aminoacyl-tRNA synthetase. the bound cysteine residuse are then chemically modified to form adenine.
the end product of this rxn is a tRNA molecule that cocntains the cysteine anticodon but is mischcarged with alanine. wWOTF is most likely to occur to the alanine residue during polypeptide synthesis of alpha- hemoglobin?
it will be incorporated into the polypeptide chain, at the site requiring cysteine
a healthy couple, who emigrated from eastern europe, brings in their 3 yo son to the office for eval of an eczematous rash. on exam the child also shows signs of intellectual disability and gait abnormaltiyand has a musty body odor.
whats the likelyhood that this couples next child will be affected with the same disease
bc PKU is autosomal .recessive
a baby with alkaptonuria. what is the classic presenting symptom in a child?
dark urine when left standing
25 year old. complains of difficulty walking.
- arthritis (large joins: knee hips) sometimes crippling.
- on xray: calcification in intervertebral disc.
- urine discoloration.
- bluish-black connective tissue, ear cartilage, and sclerae (ochronosis)
if a biopsy was done what would you expect to see? and what enzyme is deficient
pt has alkaptonuria.
would see black pigment in cartilage and joints
congenital defect in homogentisate acid oxidase.
(in the degradative pathway of tyrosine --> fumarate)
how would you diagnose alkaptonuria? what would you see?
whats the inheritance?
elevated homogentisate acid
dietary restriction (tyrosine and phenyalaine)
a young boy with an a-ketoacid dehydrogenase deficiencyis unable to degrade which acids?
he has a sweet maple odor to his urine
Isoleucine, Leucine, Valine (blocked degradation of branched amino acids due to def in branched chain a- ketoacid dehydrogenase.
"I Love Vermont maple syrup from maple trees (with B1 ranches)
urinary cyanide-nitroprusside test is diagnositic for?
cystine hexagonal stones or staghorns
hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of (COLA)
cystine, ornithine, lysine, arginine.
tx: urinary alkalinization ( potassium citrate, acetazolamine) and chelating agents (penicillamine) to inc solubity of cystine stones.
- child with pain in hands/feet (peripheral neuropathy
- lack of sweat (hypohydrosis)
- skin findings (angiokeratomas)
small dark, redtopurple raised spots, dilated surface capillaries
what lysosomal disease?
what enzyme is def?
fabrys disease you will see accumulation in what? due to a def in a galactosidase A
a infant has papable splenomegaly (most common initial sign). extensive bruising (low platelets) painless hepatosplenomegaly, and fatty yellow deposits in the sclera. on microscopy the cells resemble crumpled tissue paper. you make the diagnosis of gaucher disease.
what cell is involved in gauchers disease?
guacher cells: lipid laden macrophages filled with lipid.
young patient presents with severe bone pain. you think its sickle cell but being a badass you know its do to avacular necrosis in gauchers disease. what is the pathophysiology of this?
due to bone infarction (ischemia) bc infiltrations of gaucher cells in intremedullary space.
child of ashkenazi jew descent
splenomegaly on exam
bruising (low platelets_
what is the def enzyme and accumlation of?
what are the 3 causes of cherry red spot (spot on macula)
3. central retinal artery occlusion ( elder pt from a stroke)
- previously well, healthy child.
- weakness, loss of motor skills (progressive neurodegeration)
- enlarged liver or spleen on PE!!!
- cherry red spot!
what enzyme is def, and you will see accumulation of ?
niemann pick disease
(note; not tay sachs bc tay sachs doesnt have hepatosplenomegaly)
globoid cell leukodystrophy. what disease is this?
what enzyme is deficient?
what will accumulate in myelin?
def: galactocerebrosidase (major component of myelin aka breaks it down)
def enzyme and accumulation of?
accum: GM2 gnaglioside
3-6 month old infant
ashkenazi jew decent
exaggerated startle response
cherry red spot
def of enzyme?
accum: GM2 ganglioside
- 5-9 month old with ugly ass face (gargoylism)
- airway obstruction
corneal clouding (opacification)
whats the diagnosis? def enzyme? and what would you see accumulate in lysosomes?
inheritance pattern is AR.
accumulation of glycosaminoglycans
- (heparan sulfate, dermatan sulfate)
x linked recessive.
later onset (1-2 years) compared to hulers
- NO corneal clouding
- Behavioral probs
- learning difficulty
- trouble sitting still (can mimic ADHD)
- often aggressive behavior
whats the most likely diagnosis?
what will accumulate in lysosomes?
def: Iduronate sulfatase
accum: heparan sulfate, dermatan sulfate.
subtype of mucolipidosis disorders
named for inclusions on lighht microscopy.
similiar to hurlers disease. (clouded corneas, hypotonia/motor delay, coarse facial features, Growth failure. onset first year of like)
whats the pathopysiology of this?
Failure of processing in GOLGI apparatus
- ***Mannose-6-phosphate is NOT added to lysosome proteins
- normally M6P directs enzymes to lysosome, if not added --> enzymes secreted outside of cell.
- def intracellular enzyme lvs (WBCs, fibroblasts)
- inc extracellular enzyme lvs (plasma)
- multiple enzymes abnormal
- intraceulluar inclusions in lymphocytes and fibroblast.
a pateint comes in with HTN crisis. history of drinking wine and eating aged cheese.shes taking a MAO inhibitor. the inhibited metabolism of _______________ is causing this?
treatment (class and drug)
tx: phentolamine (a1 blocker)
A 2-year-old male presents with ear pain. The child’s parents are concerned because this is his fifth ear infection this year and he “seems to always have a cold.” Initial observation of the child reveals macrocephaly, coarse facies, and a protuberant abdomen. Physical examination reveals a red, bulging ear drum, thoracolumbar kyphosis, and hepatosplenomegaly. Ophthalmic examination reveals papilledema and mild retinal degeneration. A pedigree for this condition is shown in the exhibit. This patient is most likely deficient in
how long do your glycogen stores last during fasting?
during fasting bw meals glucagon and epinephrine stimulate use of fuel reserves. which one has a predominant major effect (according to first aid)
A. hepatic glycogenolysis
hepatic gluconeogenesis, adipose release of FFA
fatty acid SYNTHESIS occurs where?
what key shuttle transporter is required
requires CITRATE shuttle. to shuttle citrate from mitochondrial matrix into cell cytoplasm.
citrate --> acetyl-Coa --(biotin and co2 cofactors) --> malonyl-CoA --> Fatty acid synthesis (palmitate, a 16 C FA)
degratdation of FA occurs in?
what transporter is required?
what willl inhibit FA degradation
carnitine shuttle into mitochondria matrix
FA + Coa --- (fatty acyl-coa synthetase)--> Fatty Acyl-CoA --> carnitine shuttle --> FA- coA ---(B-oxidation acyl CoA dehydrogenases) --> acetyl coa ---> TCA cycle, or ketone bodies..
malonyl CoA can inhibit Fatty acyl-CoA transport
what enzyme degrates triglycerides in small intestine prodcing FFAs
what enzyme causes degradation of TGs circulating in chylomicrons and VLDL.
this enzyme is found in vascular endothelial surface and can be activated by insulin
lipoprotein lipase (LPL)
what enzyme causes degradation of TGs remaining in IDL --> LDL
hepatic TG lipase
what intracellular enzyme mostly found in adipocytes casues degradation of TGs stored in adipocytes
hormone sensitive lipase
LCAT (lecithin cholesterol acyltransferase) function ?
catalyzes esterification of 2.3 of plasma CHOLESTEROL. allows cholesterol to enter into core of HDL for transport
cholesterol estser transfer protein (CETP) function>
mediate transfer of cholesterol estero to other lipoprotein particles.
Apolipoprotein E function?
mediate remnant uptake (chylomicron, chylomicron remnant, VLDL, IDL, HDL)
Everything Except LDL
Apolipoprotein A-1 function?
Activate LCAT thus found on HDL and chylomicron
blipoprotein lipase Cofactor, that Catalyzes Cleavage of TGs
found in chylomicrons and HDL, VLDL
apolipoprotein B-48 function?
mediate chylomicron secretion into lymphatics.
found only in chylomicron and chylomicron REMNANTS
what is the only apolipoprotein not on chylomicrons
apolipoprotein B-100 function?
whats it found on
binds to LDL receptors allow them to unload there products into body.
found on VLDL, IDL, LDL
which organs take up LDL from circulation? what receptors are used for this?
liver and peripheral tissues..
infant with steatorrhea, and appears to have severe malabsorption
labs: .absent/low chylomicrons, VLDL, LDL, IDL,
on eye exam you see retinitis pigmentosa, ataixa,
on peripheral blood smear you see acanthocytosis
what is the disease. what is it due to?
deficiency in Apo B48, Apo B100.
Apo B48 ( chylomicrons from intestine)
apo B 100 (VLDL from liver)
tx: restirction of long chain fatty acids, large .doses of oral vit E!!!!
pt with recurrent pancreatitis, hepatosplenomegaly and eruptive/pruritic xanthomas (no inc risk for atherosclerosis)
blood work (high high TG >1000, Chylomicrons, and cholesterol) the plasma looks milky
diagnosis and whats the cause?
familial dyslipidemia type 1 hyperchylomicronemia
def in lipoprotein lipase or apolipoprotein C-II
- type IIa heterzygotes cholesterol >300 mg/dl LDL, cholesterol
- type IIB homozygotes > 700 LDL , cholesterol, VLDL
20 year old present with MI!!! accelerated atherosclerosis, tendon (achilles) xanthomas, corneal arcus (senilis)
diagnosis? def? inheritance pattern!!
familial hypercholesterolemia (type II)
absent or defective LDL receptors
type III dysbeta-lipoproteinemia
inc chylomicrons, VLDL
(boards and beyond says, inc cholesterol and TG)
risk of premature atherosclerosis, tuberoeruptive xanthomas,
xanthoma striatum palmare.
what is the cuase of this
defective Apo E
(apo E 2 subtype)
type IV hypertriglyceridemia.
labs. inc: VLDL, TG: HIGH (200-500)
first aid says hyperTriglyceridemia (> 1000) can cause acute pancreatitis.
whats the cause
hepatic overproduction of VLDL
in DNA replication in prokaryotes (e-coli) has a mutant strain that lacks a specific enzyme that is responsible for removing .short fragments of RNA that are base paired to DNA template what enzyme is deficient?
DNA polymerase 1. (exises RNA primer with 5 '--> 3 ' exonuclease
Cystic fibrosis inheritance patterm?
marfan syndrome is due to genetic defect on what chromosome?
chromosome 15, due to a defect of Fibrillin due to pointmutation of the FBN1 gene on chromo 15.