Step 1 Syndromes - Biochem

Front 1

Orotic aciduria

Back 1

Mutated UMP synthase

Can't convert orotic acid to UMP, so get increased orotic acid in urine, megaloblastic anemia that DN respond to B12 or folate dministration (not a defect in THF), failure to thrive.

No hyperammonemia (vs. OTC deficiency, which has increased orotic acid WITH hyperammonemia).

Rx: oral uridine administration.

Front 2

Ornithine transcarbamoylase deficiency

Back 2

key enz in urea cycle.

Accumulation of carbamoyl phosphate, which is converted to orotic acid --> orotic aciduria PLUS hyperammonemia.

Front 3

ADA deficiency

Back 3

SCID --> xs ATP and dATP imbalances nucleotide pool--> inhibits ribonucleotide reductase --> prev DNA synthesis --> decreased lymphocyte count (B and T cells).

severe recurrent bacterial, viral, fungal infections
Chronic diarrhea.
Failure to thrive
Absent thymic shadow on CXR

Front 4

Lesch-Nyhan syndrome

Back 4

Defective HGPRT (converts hypoxanthine to IMP and guanine to GMP) --> xs uric acid and de novo purine synthesis. XLR.

retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis.

He's Got Purine Recovery Trouble.

Front 5

Xeroderma pigmentosum

Back 5

mutated Nucleotide excision repeair - prevents repair of pyrimidine dimers b/c of UV light exposure.

Endonucleases release oligonucleotide containing damaged bases. DNA pol and ligase fill and reseal the gap.

Dry skin, more likely to devel melanoma and nonmelanoma skin cancers.
Manifests as sunburn-like reaction.
Die by age 30 usually.

Front 6

HNPCC

Back 6

Hereditary nonpolyposis colorectal cancer - mutated Mismatch repair - mismatched nucleotides are removed.

Front 7

Ataxia telangiectasia

Back 7

Mutated ATM kinase.

Mutated DS-DNA break repair.

Cells are more susceptible to X ray damage.

Progressive gait and truncal ataxia with onset b/n 1 and 4 y/o.
Leukemia and lymphoma are common.

Increased alpha-fetoprotein in kids 8mos old.
immunodeficiency and ataxia and ages 1-2.
Telangiectasias at aage 5y/o + poor smooth pursuit.

Front 8

I cell disease

Back 8

Inherited lysosomal storage disorder.
Failure of addition of M6P to lysosome ptns AT THE CIS GOLGI. So enz are secreted outside the cell instead of being targeted to the lysosome.

course facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal ENZ. HSM, skeletal abnormalities, plus or minus MR. Inclusion bodies in cytoplasm of cells (lysosomal ptns acting on contents of cytoplasm). Often fatal in childhood.

Front 9

Chediak Higashi syndrome

Back 9

mutation in LYST - lysosomal trafficking regulator gene - required for MT dependent sorting of endosomal proteins into late multivesicular endosomes.

Recurrent pyogenic infecitons, partial albinism, and peripheral neuropathy.

Defective formation of lysosome and phagosome (defective MT polymerization).

Front 10

Kartagener's syndrome

Back 10

PRimary ciliary dyskinesia

Immotile cilia d/t dynein arm defect. Male infertility and decreased female fertility. Chronic infections, bronchiectasis, recurrent sinusitis,

Situs inversus (dextrocardia).

More prone to infections with Pseudomonas aeruginosa (like CF).
Resp tract, eustachian, nasal, fallopian tubes, sperm flagella.

Front 11

Osteogenesis imperfecta

Back 11

Type 1 collagen defect. Problem with forming triple helix of 3 collagen alpha chains.

Bone, skin, tendon, dentin, fascia, cornea, late wound repair.

Multiple fractures with minimal trauma.
Blue sclerae
Hearing loss (abnormal middle ear bones)
Dental imperfections d/t lack of dentin.

STRONG, slippery, bloody, BM.

Front 12

Ehlers Danlos syndrome

Back 12

Type III collagen defect.

Hyperextensible skin, tendency to bleed (easy bruising), hypermobile joints.

Joint dislocation, berry aneurysms, organ rupture.

Problem with cross linking tropocollagen fibers to make collagen fibers.

Reticulin - skin, blood vessels, uterus, fetal tissue, granulation tissue.

Strong, slippery, BLOODY BM.

Front 13

Alport syndrome

Back 13

Type IV collagen defect

XLR. Progressive hereditary nephritis with hematuria, eye disorders, and deafness.

"Can't see, can't pee, can't hear me"

Basement membrane or basal lamina.

Strong, slippery, bloody BM.

Front 14

Scurvy

Back 14

Deficiency of Vitamin C.

Results in decreased hydroxylation of proline and lysine residues of preprocollagen.

Before glycosylating of pro-alpha-chain hydroxylysine residuesd and formation of procollagen (triple helix).

swollen gums, bruising, hemarthrosis, anemia, poor wound healing, loose teethc, swollen joints, weakened immune response.

Front 15

Marfan's syndrome

Back 15

Fibrillin-1 gene mutation. .

fx skeleton, heart, eyes.

Tall w/long extremities, pectus excavatum, hypermobile joints, long-tapering fingers (arachnodactyly), cystic medial necrosis of aorta -->aortic incompetence and dissecting aortic aneurysms, floppy mitral valve.

Subluxation of lenses.

Front 16

alpha-1 antitrypsin deficiency

Back 16

Can cause emphysema - excess elastase activity.

Alpha 1 antitrypsin usually ihibits elastase - elastase breaks down elastin.

Elastin gives elastic properties to skin, lungs, large arteries, elastic ligaments, vocal cords, and ligamenta flava.

Rich in proline and glycine.

Front 17

Deficiency of alpha 1,4 - glucosidase

Back 17

Pompe's disease

Type II glycogen storage disorder

Pompe's trashes the pump.

lysosomal alpha 1, 4 glucosidase is needed to hydrolyze the outer branches of glycogen. Glycogen is deposited in themyocardium. By 6th month, kids --> devel delay, feeding probs, and eventual heart failure. Skel muscle and liver are affected.

ECG --> short PR intervals with large QRS complexes (biventricular hypertrophy, cardiomegaly).

Front 18

alpha galactosidase A deficiency.

Back 18

Fabry's disease

lysosomal storage disease.

Converts ceramide trihexoside to lactosyl cerebroside.
Ceramide trihexoside accumulates --> peripheral neuropathies of the hands/feet, angiokeratomas, and cardiovascular and renal disease.

Front 19

beta glucocerebrosidase deficiency

Back 19

Gaucher's disease - lysosomal storage disease.
Converts glucocerebroside to cerebroside.

HSM, aseptic necrosis of femur, bone crises, Gaucher's cells (crumpled tissue paper macrophages)

Front 20

Glucose 6 phosphate deficiency

Back 20

Von Gierke's disease - type I glycogen storage disease.

Severe fasting hypoglycemia with large stores of glycogen in liver, hepatomegaly, increased blood lactate levels.

Front 21

Deficiency of skeletal muscle glycogen phosphorylase.

Back 21

McArdle's disease - type V glycogen storage disease.

Glycogen in muscle can't be broken down --> cramping and myoglobinuria with strenuous exercise.

Front 22

Paternal allele on csome 15 is not expressed d/t genetic imprinting.

Back 22

Prader Willi syndrome - MR, hyperphagia, obesity, hypogonadism, hypotonia.

Front 23

Maternal allele on csome 15 is not expresse d/t genetic imprinting.

Back 23

Angelman's syndrome - MR, seizures, ataxia, inappropriate laughter and big smile.

Front 24

Hypophosphatemic rickets

Back 24

X linked dominant Vit D resistant rickets. Increased phosphate wasting at proximal tubule, presents with ricket's like syndrome.

Front 25

Mitochondrial myopathies path

Back 25

Mitochondrial inheritance - mutations affecting mitochondrial function.

Present with myopathy and CNS disease. Muscle biopsy shows RAGGED RED fibers.

Front 26

Which cell signaling defect of FGF-r 3 is associated with advanced paternal age?

Back 26

Achondroplasia. Cell signaling defect of FGF-r 2 which results in:

dwawrfism, short limbs, larger head, normal trunk size.

Front 27

Mutation in PDK-1 that results in bilateral massive enlargement of kidneys, flank pain, hematuria, HTN, and progressive renal failure

Back 27

Autosomal dominant polycycstic kidney disease.

AD. On Csome 16.

A/w polycystic liver disease, berry aneurysms, mitral valve prolapse.

Front 28

Mutation on Csome 5 of APC gene.

Back 28

FAmilial adenomatous polyposis.

Colon is covered in adenomatous polyps after puberty. Progressed to colon cance runless colon is resected.

Front 29

Elevated LDL cholesterol 500/dL, tendon xanthomas, severe atherosclerotix disease, MI before age 20.

Back 29

Autosomal dominant, homozygote with Familial hypercholesterolemia (HLD type IIa).

Elevated LDL d/t defective or absent LDL-r.

Heterozygotes (1:500) have chol ~300mg/dL while homozygotes have chol ~700mg/dL.

Front 30

Spectrin defect --> hemolytic anemia.

Back 30

Hereditary spherocytosis. Spheroid erythrocytes d/t spectrin or ankyrin defect. Hemolytic anemia and increased Mean corpuscular Hgb concentration.

Splenectomy is curative.

Front 31

CAG repeat disorder

Back 31

Huntington's - csome 4

Depression, progressive dementia, choreiform movmenet,s caudate atrophy, decreased levels of GABA and Ach in brain. Sx. manifest between 20 and 50.

Anticipation genetics.

Front 32

Ret gene mutations

Back 32

MEN (multiple endocrine neoplasias) - 2A, 2B (MEN type 1 is not a/w Ret oncogene.
Familal tumors of endocrine glands, incl pancreas, parathyroid, pituitary, thyroid, and adrenal medulla.

Front 33

Neurofibromatosis type 1 (von recklinghausen's disease)

Back 33

Long arm of csome 17.

cafe-au-lait spots, neural tumors, lisch nodules (pigmented iris hamartomas).
Skeletal disorders (scoliosis, e.g.), and optic pathway gliomas.

Front 34

Neurofibromatosis type 2

Back 34

NF2 gene on csome 22.

Bilateral acoustic schwannomas, juvenile cataracts.

Front 35

Tuberous sclerosis manifestations

Back 35

HAMARTOMAS

Hamartomas (cortical and retinal)
Angiofibromas (adenoma sebaceum - facial lesions)
Mental retardation
Ash leaf spots
Rhabdomyomas (cardiac)
Tuberous sclerosis
O - autosomal dOminant
M
Aastrocytomas
Seizures

also, renal cysts and renal angiomyolipomas.

Front 36

VHL gene deletion

Back 36

Von-Hippel Lindau disease

Hemangioblastomas of retina/cerebellum/medulla.

Most pts developmultiple bilateral renal cell carcinomas and other tumors.

Constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors.

Front 37

deletion of CFTR gene path

Back 37

Cystic fibrosis.

Csome 7.

CFTR channel actively secretes Cl- in lungs and GI tract + reabsorbs Cl- from sweat.

Defective channel --> secretion of abnormally thick mucus that plugs lungs, pancreas, and liver --> recurrent pulmonary infections (Pseudomonas spp, H. influenzae, and S. aureus), chronic bronchitis, bronchiectasis, pancreatic insufficiency *malabsorption and steatorrhea), nasal polyps, and meconium ileus in newborns.

Infertility in males d/t bilateral absence of vas deferens.

Fat soluble vitamin deficiencies.

Failure to thrive in infance.

MOST COMMON LETHAL GENETIC DISEASE IN WHITE POPULATION.

Test: concentration of Cl- ions in sweat test.

Rx: N-acetylcysteine to loosen mucus plugs (cleaves disulfide bonds within mucus glycoproteins.)

Front 38

Wernicke's encephalopathy (or Korsakoff syndrome)- what's the cause and manifestation?

Back 38

Thiamine (B1) deficiency - often associated with chronic alcoholism and secondary dietary insufficiency or impaired intestinal absorption.

Ataxia, lateral gaze palsy, confusion.
with korsakoff psychosis --> anterograde and retrograde amnesia, often with confabulation.

Damage to medial dorsal nucleus of thalamus, mamillary bodies.

Deficiency of thiamine causes shunting of pyruvate to lactate, resulting in lactic acidosis. Needed for Pyruvate dehydrogenase in coversion of pyruvate to acetyl-coA.

Front 39

Viral hepatitis findings - which is higher, ALT or AST?

Back 39

ALT is MUCH much higher.

Front 40

Alcoholic hepatitis - which is higher, ALT or AST?

Back 40

AST is much higher - A Scotch and Tonic.

Front 41

High urine metanephrine level

Back 41

Pheochromocytoma.

presents with h/a, palpitations, and diaphoresis with severe HTN.

Front 42

High urine protein.

Back 42

Nephrotic syndrome

Edema, hypoalbuminemia, and HLD.

Front 43

Low serum haptoglobin.

Back 43

Intravascular hemolysis. Haptoglobin binds to free heme.

Front 44

Dry Beri beri

Back 44

deficiency of Vitamin B1 (thiamine)
Polyneuritis, symmetrical muscle wasting.

Front 45

Wet beri beri

Back 45

Deficiency of vitamin B1 (thiamine)

dilated cardiomyopathy, edema

Front 46

Fragile X syndrome

Back 46

XL dominant, variable penetrance. Genetic anticipation from increasing trinucleotide repeats in FMR-1 gene.

CGG trinucleotide repeat disorder.

Fragile X = eXtra large testes, jaw, ears.

Marked mental retardation, with degree of retardation increasing as pt ages. Long, large faces w/prominent forehead and jaw, marcroorchidism.

Autistic behaviors - poor eye contact, perseveration, impulsivity.

Females are carriers.

Front 47

Hypotonia, palmar crease, MR, epicanthal folds, endocardial cushion defect?

Back 47

Downs - trisomy 21.

MR, flat facies, prominent epicanthal folds, simian crease, gap b/n 1st 2 toes, ASD common cause of congenital heart disease, increased risk of ALL and Alzheimer's disease before age 35.

95% d/t meiotic nondisjunction of homologous csomes (assoc w/ AMA).

Pregnancy quad screen:
decreased alpha fetoprotein, increased beta-hCG, decreased estriol, increased inhibin,A.

Front 48

Micrognathia, low set ears, syndactyly, clenched hands (5th overrides 4th, index overrides middle), rocker-bottom feet, prominent occiput, congenital heart disease.

Back 48

Edward's syndrome

Trisomy 18

Few pts survive past 1st year of life.

Quad screen: decreased alpha fetoptn, decreased beta-hCG, decreased estriol, normal inhibin A (vs. Down's, which has decreased alpha-FP and estriol, but INCREASED beta hCG and inhibin A).

Front 49

47 XXY or 46XY/47XXY mosaicism.

Back 49

Klinefelter's syndrome.

Gynecomastia, small testes, azoospermia, effeminate body type, developmental delay, learning disabilities.

Not inherited.

Front 50

cleft lip/palate, low set ears, congenital heart disease, microcephaly, MR, polydactyly, micrgnathia, optic abnormalities.

Back 50

Patau's syndrome - Trisomy 13

Many pts don't survive beyond first month of life.

quad screen: decreased beta-hCG, decreased PAPP-A, increased nuchal translucency.

Front 51

Duchenne's muscular dystrophy mutation

Back 51

Dystrophin gene - frameshift mutation --> accelerated muscle breakdown. Dystrophin helps anchor muscle fibers, esp in skeletal and cardiac muscle.

Weakness BEGINS in pelvic girdle muscles, progresses superiorly.

Pseudohypertrophy of calf muscles d/t fibrofatty replacement of muscle, cardiac myopathy.

Gower's maneuver to stand up. Onset before Age 5.

DMD is the longest known human gene.

Dx with increased CPK and muscle biopsy.

Front 52

Becker's muscular dystrophy mutation

Back 52

X linked mutated dystrophin gene. Less severe than duchenne's.

Onset in adolescence or early adulthood.

Dx. with increased CPK or muscle biopsy.

Front 53

Name these trinucleotide repeat disorders:

CGG
GAA
CAG
CTG

Back 53

Fragile X syndrome - CGG
Friedrich's ataxia - GAA
Huntington's disease -CAG
Myotonic dystrophy - CTG

Tri(nucleotide) hunting for my fried eggs (X).

X-Girlfriend's First Aids Helped Ace My Test. (use the first letter of the disorder and the middle letter of the repeat)

Front 54

What is the genetic abnormality in an infant with microcephaly, moderate to severe MR, high-pitched crying/mewing, epicanthal folds, and cardiac abnormalities?

Back 54

Cri-du-chat syndrome - microdeletion of short arm of Csome 5 (46XX or Xy, 5p-)

Also have VSD.

Front 55

What is the genetic abnormality in an infant with elfin facies, intellectual disability, hypercalcemia, well-developed verbal skills, friendliness with strangers, and cardiovascular problems?

Back 55

Williams syndrome - microdeletion of long arm of Csome 7 (deleted region includes elastin gene.

They have increased sensitivity to Vitamin D.

Front 56

DiGeorge syndrome genetic abnormality.

Back 56

22q11

Front 57

Digeorge presentation

Back 57

cleft palate, abnormal facies, thymic aplasia (T cell def), Cardiac defects, hypocalcemia secondary to parathyroid aplasia, microdel of 22q11

CATCH 22

Aberrant devel of 3rd/4th branchial pouches.

Front 58

Velocardiofacial syndrome genetic abnormality and presentation

Back 58

22q11

palate, facial, and cardiac defects.

d/t aberrant 3rd/4th branchial pouch development.

Front 59

Deficiency in the conversion of sphingomyelin to cerebroside

Back 59

Niemann-Pick disease

Cherry red spot on macula, foam cells.

HSM, failure to thrive, progressive CNS deterioration. Hepatocytes and Kupffer cells have foamy, vacuolated appearance. Boy will die by age of 3.

Front 60

Hepatosplenomegaly, failure to thrive, progressive CNS detereioration, Kupffer cells have foamy, vacuolated appearance.

Back 60

Niemann-Pick disease. Accumulation of sphingomyelin and cholesterol in parenchymal and reticuloendothelial cells d/t defective sphingomyelinase. Converts sphingomyelin to cerebroside.

Front 61

Accumulation of cerebroside in lysosomes.

Back 61

Krabbe's disease. Beta-galactosidase deficiency - converts galactocerebroside to cerebroside.

Front 62

Accumulation of ganglioside M3 in lysosomes.

Back 62

Tay Sachs disease. Accumulation is d/t deficient Hexosaminidase A (converts ganglioside M2 to ganglioside M3).

Front 63

Niemann pick

Back 63

sphingomyelinase - No man picks his nose with his Sphinger

accum sphingomyelin

neurodegen, cherry red macula, foam cells

Front 64

fabry's

Back 64

alpha galactosidase A

cereamide trihexoside accum

periph neuropathy, CVD

Front 65

gaucher's

Back 65

glucocerebrosidase

glucocerebroside accum

HSM, bone crises, crumpled tissue paper macrophages

Front 66

tay sachs

Back 66

hexosaminidase A - tay sachs LACKS HeXosaminidase A

GM2 ganglioside accum.

neurodegen, cherry red spot macula, onion skin lysososmes, no HSM

Front 67

krabbe's

Back 67

galacrocerebrosidase

galactocerebroside accum

periph neuropathy, devel delay, globoid cells

Front 68

metachromatic leukodystrophy

Back 68

arylsulfatase A

cerebroside sulfate accum

central/periph demyelination with ataxia, dementia.

Front 69

Hurler's

Back 69

alpha-L-iduronidase

heparan sulfate, dermatan sulfate accum

devel delay, gargoyl, airway obstruc, corneal clouding, HSM

Front 70

Hunter's

Back 70

iduronate sulfatase

heparan sulfate, dermatan sulfate accum - XLR

mild hurler's (devel delay, gargoyl, airway obstruction, HSM)

NO CORNEAL CLOUDING - Hunters SEE CLEARLY, and aim for the X (XLR)

Front 71

Deficiency of G6Ptase

Back 71

Von Gierke's - glycogen storage dz type I

AR

severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, Hepatomegaly.

Front 72

Deficiency of lysosomal alpha 1,4, glucosidase (acid maltase)

Back 72

Pompe's disease - type III glycogen storage dz

AR - Pompe's trashes the pump (heart, liver, muscle)

Cardiomegaly and systemic findings --> early death.

Front 73

Deficiency of debranching enzyme (alpha 1,6, glycosidase).

Back 73

Cori's disease - glycogen storage Type III

AR, gluconeogenesis intact

Milder type I (severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, hepatomegaly), BUT WITH NORMAL LACTATE!

Front 74

Major abnormality in malignant carcinoid syndrome

Back 74

increased tryptophan metabolism

causes pellagra (vit B3 def since tryptophan is required substrate for niacin.)

Diarrhea, dermatitis, dementia.

Front 75

Major abnormality in Hartnup disease

Back 75

decreased tryptophan absorption

leads to pellagra (Vit B3 def since tryptophan is required substrate for niacin synthesis)

Diarrhea, dermatitis, dementia.

Front 76

Which vitamin deficiency results in macrocytic, megaloblastic anemia?

Back 76

B12, B9

BUT B9 has no neurological sx, whereas B12 does (paresthesias, subacute combined degereation d/t myelin degen in dorsal and lateral tracts of spinal cord).

B9 = Most common vitamin def in US. Pregnancy and alcoholism.

Front 77

Which deficiency results in microcytic anemia?

Back 77

Iron-deficiency anemia

Front 78

Vitamin deficiency leading to bone pain, deformity in a child. Bowed legs.

Back 78

Vitamin D. This is Rickets.

In an adult, it would be osteomalacia, which is bone pain and muscle weakness.

Hypocalcemic tetany is another possibility.

Watch out for breast milk being low in vitamin D, especially in dark-skinned patients.

low Vit D --> hypocalcemia --> high PTH --> Ca2+ mobilized from bone, decreased renal Ca2+ excretion, and increased renal PO42- excretion and impaired bone mineralization.

Front 79

Which deficiency leads to a hemolytic anemia?

Back 79

Vitamin E (E for Erythrocytes)

Vit E is an antioxidant that protects erythrocytes and membranes from oxidative free-radical damage.

increased fragility of erythrocytes, muscle weakness, posterior column and spinocerebellar tract demylelination --> ataxia and peripheral neuropathy.

Front 80

Defective porphobilinogen deaminase

Back 80

Acute intermittent porphyria.

Defective heme synthesis.

Sx: Abdominal pain, wine-colored urine, neuropathy, psychological disturbances.

Front 81

Mutated keratin 14 or 15

Back 81

Epidermolysis bullosa

these are the major keratins in basal epithelial cells --> skin that readily breaks and forms blisters with minor trauma.