First Aid: Genetics - Down And Dirty

Front 1

Kid with ortic acid in their urine, megaloblastic anemia, and failure to thrive with normal ammonia levels?

Back 1

Orotic aciduria = AR defect in orotic acid phosphoribosyltransferase or orotidine 5'phosphate decarboxylase.Tx with oral uridine.

Front 2

Early recurrent infections of all types with B and T cell deficiency with diarrhea and failure to thrive?

Back 2

SCID = most common is X linked defect in IL-2 or adenosine deaminase deficiency (excess ATP inhibits ribonucleotide reductase = DNA synthesis prevented = dec WBC count)

Front 3

Retarded aggressive boys that bit their lips/fingers with gout and choreoathetosis

Back 3

Lesch-Nyhan = x linked absence of HGPRT = defective purine salvage - can tx the excess uric acid with allopurinol.

Front 4

Dry skin with increased susceptibility to melanoma and other cancers

Back 4

xeroderma pigmentosum = endonuclease mutuation - defective nucleotide excision repair = can't fix thymidine dimers caused by UV`

Front 5

Coarse facial features, clouded corneas, restricted joint movement, and high plasma lysosomal enzymes with death by 8.

Back 5

I-cell disease = mannose-6 phosphate isn't added to lysosome proteins = secreted out instead of being targeted to lysosome

Front 6

Recurrent pyogenic infections, partial albinism, and peripheral neuropathy

Back 6

Chediak-Higashi = AR defect in LYST gene = microtubule polymerization defect = decreased phagocytosis

Front 7

80% chance of colorectal cancer (always proximal) with no polyps on colonoscopy

Back 7

Hereditary nonpolyposis colorectal cancer/Lynch syndrome = AD mutation of exonuclease responsible for mismatch repair = microsatellite instability and build up

Front 8

Infertility, bronchiectasis, and recurrent sinusitis with situs inversus

Back 8

Kartagener's syndrome = dyneine arm defect = immotile cilia

Front 9

Hyperextenisble skin, tendency to bleed with easy bruising, and hypermobile joints

Back 9

Ehlers-Danlos = Faulty collagen synthesis - mostly type III (AD/AR - defect in proteolytic cleavage to tropocollagen) Assoc with berry aneurysm, joint dislocation, and organ rupture

Front 10

Multiple fractures, blue sclera, hearing loss, and dental imperfections due to lack of dentin

Back 10

Osteogenesis imperfects = AD mutation in type I collagen = defective alpha triple helix formation. Type II is more severe and fatal.

Front 11

Progressive nephritis and hearing loss with ocular disturbances

Back 11

Alport's = X linked defect in type IV collagen (structural component in basement membrane of eyes, kidney, and ears)

Front 12

Tall with long extremitities, pectus excavatum, hyperextensive joints, long tapering fingers/toes with floppy mitral valve

Back 12

Marfan's = AD fibrillin defect = no scaffolding for extracellular tropoelastin. Assoc with aortic cystic medial necrosis, berry aneurysm, and subluxation of lenses

Front 13

Panacinar emphysema with PAS+ globules in the liver and increased risk for hepatocellular carcinoma

Back 13

Alpha1-antitrypsin defeciency (Co-dominant trait) = no elastase inhibition = no elastin in lungs and buildup of misfolded protein in hepatocytes

Front 14

Short, fat, and retarded with hyperphagia and hypogonadism that present at birth with hypotonia and poor feeding. Characteristic almond shaped eyes and down-turned mouth.

Back 14

Prader-Willi = 15q11-q13 microdeletion on the paternal chromosome. Dx with FISH. Tx with limiting food and GH for stature

Front 15

Retards with seizures that walk like puppets (jerky ataxia) and laugh inappropriately

Back 15

Angelman's syndrome = 15q11-q13 microdeletion on the maternal chromosome.

Front 16

Acute loss of central vision due to degeneration of the retinal ganglion cells and axons

Back 16

Leber's hereditary optic neuropathy = mitochondiral inheritance

Front 17

Bow-legs, pectus cavinatum, lumbar lordosis, and rachitic rosary due to phosphate wasting at the proximal tubule

Back 17

Hypophosphatemic rickets = x linked dominant = "vitamin D resistant ricket's"

Front 18

Short limbs with normally sized head and trunk with an old father

Back 18

Achondroplasia = AD defect of Fibroblast Growth Factor 3

Front 19

Bilateral massive kidney enlargement with cysts = flank pain, hematuria, htn, and progressive renal failure

Back 19

ADPKD = AD defect of APKD1 on chromosome 16. Assoc with polycystic liver disease, berry aneurysms, and mitral valve prolapse

Front 20

Colon covered with adenomatous polyps after puberty with 100% progressing to cancer

Back 20

Familial adenomatous polyposis = AD deletion of APC gene on chromosome 5

Front 21

High LDL levels with severe arherosclersis and tendon xanthomas

Back 21

Familial hyperlipidemia type IIA = AD defect in LDL receptors on chromosome 19 (homo = LDL of 700 with MI before 20)

Front 22

Telangiectasia (flat, red marks = capillary dilation), recurrent epistaxis, skin discoloration, and atteriovenous malformations

Back 22

Hereditary hemorrhagic telangiectasia (osler-weber-rendu syndrome) = AD disorder of blood vessels

Front 23

Hemolytic anemia with increased MCHC that can be cured with a splenectomy

Back 23

Hereditary spherocytosis = AD defect in spectrin or ankyrin. Dx with osmotic fragility test

Front 24

Depression, progressive dementia, involuntary rapid/jerky movements in a patient that's 20-40

Back 24

Huntinton's = AD trinucleotide expansion of CAG (glutamine) in huntingtin gene on chromosome 4 = caudate atrophy with decreased GABA and ACh

Front 25

Tumors of the parathyroid, pituitary, and pancreas = often present as kidney stones/stomach ulcers

Back 25

Wermers, MEN I = AD

Front 26

Pheochromocytoma, medullary thyroid cancer (calcitonin secreting), and parathyroid tumors

Back 26

Sipple's, MEN 2A = AD, assoc with ret gene

Front 27

Pheochromocytoma, medullary thyroid cancer (calcitonin secreting), and oral/GI ganglioneuromatosis with Marfanoid habitus

Back 27

MEN 2B = AD, assoc with ret gene

Front 28

Cafe-au-lait spots with axillary freckling, neural tumors (schwann cells, fibroblasts, or neurites) with pigmented iris hamartomas

Back 28

Neurofibromatosis type I (Von Recklinghausen's disease) = AD defect on long arm of 17. Assoc with skeletal disorders, optic gliomas, pheochromocytomas, and increased tumor risk.

Front 29

Bilateral acoustic neuromas with juvenile cataracts

Back 29

Neurofibromatosis II = AD defect in NF2 gene on chromosome 22

Front 30

Retard with facial adenoma sebaceum, ash leaf spots, retinal hamartomas, seizures, renal angiomyolipomas, and cardiac rhabdomyomas.

Back 30

Tuberous sclerosis = AD disorder with incomplete penetrance and variable presentation. Assoc with astrocytomas.

Front 31

Hemangioblastomas in retina/cerebellum/medulla with bilateral renal cell carcinoma and sometime pheochromocytoma

Back 31

VonHippel-Lindau disease = deletion of VHL gene (tumor suppressor) on chromosome 3 = HIF is always active = angiogenic GF active

Front 32

Recurrent pulmonary infections, pancreatic insufficiency (with fat soluble vit deficiency), meconium ileus (abd distension and vomitting soon after birth), lack of vas deferens, and failure to thrive

Back 32

Cystic fibrosis = AR defect in CFTR on chromosome 7 = abnly thick mucous in lungs and GI due to failure of Cl secretion and increased sweat Cl due to reabs failure.
Tx = N-acetylcysteine to loosen mucous plugs

Front 33

Weakness in the pelvic girdle of a 5 y/o that progresses superiorly. Psuedohypertrophy of the calf muscles and cardiomyopathy

Back 33

Duchenne's muscular dystrophy = x linked frame shift mutation = deletion of dystrophin gene (muscle anchor)

Front 34

Weakness in the pelvic girdle of a 20 y/o that progresses superiorly.

Back 34

Becker's muscular dystrophy = x linked mutation in dystrophin gene

Front 35

Retards with big nuts, jaw, and ears. Plus autism and mitral valve prolapse.

Back 35

Fragile X syndrome = x linked trinucleotide repeat in CGG (arginine) that affects methylation and expression of FMR1 gene. Assoc with chromosomal breakage

Front 36

Staggering gait, frequent falling, nystagmus, dysarthria, high arched feet (pes cavus), hammer toes, kyphoscoliosis, and hypertrophic cardiomyopathy

Back 36

Friedrich's ataxia = AR trinucleotide repeat of GAA (glutamate) of frataxin gene = mitochondrial dysfunction

Front 37

Muscle wasting and weakness first noted in face/jaw muscles with severe cognitive problems

Back 37

Myotonic dystrophy = trinucleotide repeat of CTG (leucine) in DMPK gene

Front 38

Retards with flat faces, almond shaped eyes, simian crease, ASD, duodenal atresia, increased ALL risk and alzheimers after 35

Back 38

Down Syndrome = chromo 21 trisomy (95% = nondisjunct, assoc with old moms) = dec AFP and estriol with increased HCG and inhibin A. Nucal translucency on U/S. Most common congenital retardation

Front 39

Retards with rocker bottom feet, small jaws, low set ears, clenched hands, prominent occiput and congenital heart disease (VSD or valve defects)

Back 39

Edward's syndrome = trisomy of chromosome 18 = decreased AFP, estriol, and HCG. Death within one year

Front 40

Retards with rocker bottom feet, small eyes and head, cleft palate, holoprosencephaly (no hemispheres), polydactyly, and congenital heart defects (VSD, PDA, ASD).

Back 40

Patau's syndrome = trisomy of chromosome 13 = death by 1 year

Front 41

Retard with small head, epicanthal folds, cardiac abnormalities (VSD), and a high pitched mew

Back 41

Cri-Du-Chat = microdeletion of short arm of chromosome 5

Front 42

Retards with elfin facies, hypercalcemia, cardiovascular issues (often aortic stenosis), and well developed verbal skills

Back 42

William's syndrome = microdeletion on long arm of chromosome 7

Front 43

Cleft palate, abnormal facies, thymic aplasia (t cell deficiency), cardiac defects, hypocalcemia due to parathyroid aplasia

Back 43

Microdeletion of chromosome 22q11 = aberrant development of 3rd and 4th branchial pouches = variable presentation = diGeorge if thymic, Velocardiofacial if facial.

Front 44

Hemolytic anemia due to failure of anaerobic glycoloysis

Back 44

95% have pyruvate kinase deficiency, 4% = phosphoglucose isomerase. RBC swelling and lysis due to inability to maintain activity of the NA-K-ATPase pump

Front 45

Neurologic defects with lactic acidosis due to a buildup of pyruvate and alanine

Back 45

Pyruvate dehydrogenase deficiency - can be congenital or caused by a B1 deficiency (alcoholics). Tx with increased ketogenic aa's = lysine and leucine.

Front 46

Hemolytic anemia deu to decreased NADPH in RBCs (precipitated by oxidating agents or infection)

Back 46

G6PD deficiency - xlinked. Most common human enzyme deficiency. See heinz bodies and bite cells.

Front 47

Hypoglycemia, jaundice, cirrhosis, and vomiting with accumulation of fructose-1-phosphate

Back 47

Fructose intolerance - AR aldolase B deficiency = decreased phosphate = inhibs glycogenolysis and gluconeogenesis.
Tx by limiting fructose and sucrose intake

Front 48

Fructose in the blood and urine of an otherwise healthy individual.

Back 48

Essential fructosuria = AR defect in fructokinase. Benign since fructose can't enter cells but can still be phosphorylated with hexokinase.

Front 49

Early onset of failure to thrive, jaundice, HMG, infantile cataracts, and mental retardation.

Back 49

Classic galactosemia = AR absence of galactose-1-phosphate uridyltransferase = toxic accum (galactitol = cataracts)
Tx with no lactose or galactose in diet
Differentiate from Hurler's by lack of coarse facies.

Front 50

Galactose in blood and urine with infantile cataracts. Presents initially as failure to track objects or develop social smile.

Back 50

Galactokinase deficiency - AR, relatively mild. Limit galactose in diet to prevent galactitiol accumulation

Front 51

Bloating, cramps, and osmotic diarrhea after eating pizza

Back 51

Lactase deficiency - can be AR or due to loss of brush border. Avoid dairy (lactose = galactosyl beta 1,4 glucose)

Front 52

Tremor (asterixis = flapping with extension), slurring of speech, somnolence, vomiting, cerebral edema, and blurring of vision

Back 52

Hyperammonemia - acquired (liver disease) or hereditary defect in urea cycle. Inc ammonia depletes alpha-ketoglutarate, inhibiting the TCA cycle.
Tx = limit protein intake. Give Benzoate or phylbutyrate to bind and excrete aa's

Front 53

Tremor (asterixis = flapping with extension), slurring of speech, somnolence, vomiting, cerebral edema, and blurring of vision with orotic acid in blood and urine and decreased BUN

Back 53

Ornithine trascarbamoylase deficiency = x-linked. Most common urea cycle diseorder leading to excess carbamoyl phosphate that's converted to orotic acid.
Tx with benzoate (binds aa's)

Front 54

Mental retardation, growth retardation, seizures, fair skin, eczema, and musty body odor.

Back 54

Phenylketonuria = AR deficiency in phenylalanine hydroxylast or tetrahydrobiopterin cofactor = increased phenylketones (phenylacetate and phenylpyruvate).
Tx - decrease phenylalanine and increase tyrosine in diet

Front 55

Dark CT with onchronosis (blue-grey skin), pigmented sclera, debilitating arthralgias and urine that turns dark on standing

Back 55

Alkaptonuria (ochronosis) - AR deficiency of homogenestic acid oxidase = benign except for possible arthralgias from homogenistic acid buildup

Front 56

Very high homocysteine in urine with mental retardation, osteoporosis, Marfanoid habitus, lens subluxation, and atherosclerosis

Back 56

Homocysteinuria - AR defect in cystathionine synthase (quantity or affinity for pyridoxal phosphate) or deficiency in homocysteine methyltransferase.
Tx - decrease methionine, increase cysteine, B12, and B6

Front 57

Cysteine kindney stones

Back 57

Cystinuria = AR defect defect in renal transporter for cysteine, ornithine, lysine, and arginine in the PCT of the kidney.
Tx with urine alkalinization via acetazolamide

Front 58

Severe CNS defects, mental retardation, and death in a kid with pee that smells like burnt sugar

Back 58

Maple syrup urine disease = AR defect in branched amino acid degredation (Ile, Leu, Val) due to decreased alpha-ketoacid dehydrogenase

Front 59

Dementia, dermatitis, and diarrhea in a patient with increased tryptophan in their urine

Back 59

Hartnup disease = AR defect in neutral aa transport on renal and GI cells
Tx - niacin

Front 60

Severe fasting hypoglycemia with increased blood lactate and uric acid and fatty liver

Back 60

VonGierke's disease (glycogen storage type I) = glucose-6-phosphate deficiency = can't do glycogenolysis or gluconeogenesis

Front 61

Cardiomegly and muscle weakness with PAS+ granules in the myocyte. Death by 3.

Back 61

Pompe's disease = glycogen storage II = deficiency in lysosomal alpha 1,4 glucosidase (acid maltase)

Front 62

Painful muscle crams and myoglobinuria with strenuous exercise

Back 62

McArdel's disease (glycogen IV) = deficiency in myophophorylase (glycogen phosphorylase = no glycogenolysis)

Front 63

Fasting hypoglycemia with dextrin accumulation in hepatocytes and normal blood lactate levels

Back 63

Cori's disease (glycogen III) = deficiency in debranching enzyme alpha-1,6-glucosidase. Gluconeogenesis is intact.

Front 64

Peripheral neuropathy with angiokeratomas, heart disease and, sometimes, renal failure

Back 64

Fabry's disease = X linked defect in alpha-galactosidase A = accumulation of ceramide trihexoside

Front 65

HSM, aseptic femur necrosis and macrophages that look like crumpled tissue paper

Back 65

Gaucher's disease = AR defect in beta-glucocerebrosidase = build up of glucocerebroside (most common lysosomal storage disease)

Front 66

Progressive neurodegeneration, HSM, and cherry red spot on macula with foam cells

Back 66

Niemann-Pick disease = AR defect in Spingomyelinase = build up of sphingomyelin. Patients die by 3.

Front 67

Progressive neurodegeneration, developmental delays, and cherry red spot on macula with onion skin lysosomes

Back 67

Tay-Sachs disease = AR defect in hexosaminidase A = build up of GM2 gangliocide. Patients die by 3.

Front 68

Peripheral neuropathy, developmental delays, optic atrophy, and globoid cells

Back 68

Krabbe's disease = AR defect in galactocerebrosidase = build up in galactocerebroside

Front 69

Central and peripheral demyelination with ataxia and dementia

Back 69

Metachromatic leukodystrophy = AR defect in arylsulfatase A = build up of cerebroside sulfate

Front 70

Developmental delay, gargoylism, ariway obstruction, corneal clouding and HSM

Back 70

Hurler's syndrome = AR defect in alpha-L-iduronidase = build up of heparan sulfate and dermatan sulfate (mucopolysaccharidosis)

Front 71

Gargoylism, ariway obstruction, corneal clouding and HSM

Back 71

Scheie's = milder form of Hurler's without the mental retardation

Front 72

Developmental delay, gargoylism, ariway obstruction, aggression and HSM

Back 72

Hunter's syndrome = XR defect in Iduronate sulfatase = build up of heparan sulfate and dermatan sulfate (mucopolysaccharidosis)

Front 73

Lysosomal storage disease ddx for Ashkenazi Jews?

Back 73

Tay-Sachs, Niemann-Pick, and Gaucher's

Front 74

Hypoketotic hypoglycemia with weakness and hypotonia due to a toxic build up of long chain fatty acids.

Back 74

Carnitine deficiency = can't transport LCFAs into the mitochondria - can be primary or secondary due to formation of acylcarnitine adducts

Front 75

Hypoketotic hypoglycemia with increased levels of dicarboxylic acids

Back 75

Acyl-CoA dehydrogenase deficiency (impaired beta oxidation)

Front 76

Pancreatitis, HSM, and eruptive, pruritic xanthomas without atherosclerosis

Back 76

Type I dyslipidemia - due to lipoprotein lipase deficiency = increased levels of TG, cholesterol, and chylomicrons.
Tx with heparin test to measure levels of enzyme (released from endothelium)

Front 77

Accelerated atherosclerosis, tendon xantomas and corneal arcus (white or gray opaque ring in the corneal margin)

Back 77

Type II dyslipidemia - AD absence/defect of LDL receptors = Increased LDL levels

Front 78

Congenital cause of pancreatitis (lipid buildup)

Back 78

IV dyslipidemia = elevated blood levels of TG with increased VLDL due to hepatic overproduction

Front 79

Failure to thrive, steatorrhea, acanthocytosis, ataxia, and night blindness within first few months of life

Back 79

Abetalipoproteinuria = can't syntheisize lipoproteins due to AR deficiencies in apoB-100 and b-48 = lipids accumulate in enterocytes.
Tx with increased vitamin E

Front 80

Infertile tall, long-armed man with gynecomastia, female hair distribution and small nuts and possible developmental delay

Back 80

Klinefelter's (47 XXY) = dysgenesis of the seminiferous tubules and abnl leydig cell function = decreased inhibin and testosterone = Increased LH, FSH, and estrogen

Front 81

Short webbed neck female without secondary sex characteristics presenting for amenorrhea

Back 81

Turner's (45XO) = decreased estrogen with increase LH and FSH = streak ovary, preductal aortic coarctation and bicuspid aortic valve

Front 82

Phenotypically normal male that's very tall with severe acne and normal fertility

Back 82

47XYY
1-2% are antisocial

Front 83

Both ovary and testicular tissue are present with ambiguous genitalia

Back 83

True hermaphrodites = 46XX or 47XXY

Front 84

Normal appearing female with testicles in labia majora and a rudimentary vagina without a uterus

Back 84

Androgen insensitivity syndrome (46XY) = AR defect in the androgen receptor = increased testosterone, estrogen, and LH with normal FSH

Front 85

Ambiguous genitalia at birth with normal internal genitalia and the development of a penis at puberty

Back 85

5-alpha-reductase deficiency = can't convert testosterone to DHT - normal testosterone and estrogen with increased/nl LH

Front 86

Recurrent bacterial infections after 6 months of age with a decrease in all Ig

Back 86

Bruton's agammaglobulinemia = XR defect in tyrosine kinase gene BTK, blocking B cell differentiation = decreased number of mature B cells with defect in opsonization

Front 87

Sever pyogenic infections early in life with increased IgM but very little IgG, IgA, and IgE

Back 87

Hyper-IgM syndrome = XR defective CD40L on T's = inability to class switch

Front 88

Sinus and lung infections with milk allergies, atopy, asthma, and diarrhea

Back 88

IgA deficiency due to plasma cell maturation defect (isotype switching defect) = anaphylaxis if given blood transfusion with IgA

Front 89

Tetany with recurrent viral/fungal infections and truncus arteriosus or tetrology of fallot

Back 89

DiGeorge's = 22q11 = failure of 3rd and 4th pouch development = Decreased T cells, PTH, and Calcium with absent thymic shadow on CXR

Front 90

Disseminated mycobacterial infections

Back 90

IL-12 deficiency = decreased Th1 response = decreased INF-gamma

Front 91

Coarse facies (broad nose, frontal bossing, retained primary teeth), cold staph abscesses, and eczema

Back 91

Hyper-IgE (Job's) = Th1's don't produce INFgamma = PMNs don't respond to chemotaxis = increased IgE and eosinos

Front 92

Candida infections of the skin and mucous membranes

Back 92

Chronic mucocutaneous candidiasis = T cell dysfunction (Hematogenous spread stopped by PMNs)

Front 93

Recurrent viral, bacterial, fungal, and protozoal infections that can be treated with a bone marrow transplant. Plus diarrhea and failure to thrive

Back 93

SCID: most common is XR IL-2 defect but can also be adenosine deaminase deficiency or no MHCII = no T cell activation or increase in adenine which is toxic to B's and T's = only NK cells available to kill things

Front 94

Cerebellar defects (ataxia), spider angiomas, and IgA deficiency with poor eye smooth persuit

Back 94

Ataxia-telangectasia = Defect in DNA repair = radiation sensitivity and increased risk of lymphoma/leukemia with decreased IgA and death by 25

Front 95

Thrombocytopenix purpura, recurrent pyogenic infections, and non-flexor eczema

Back 95

Wiskott-Aldrich = XR defect resulting in progressive deletion of B's and T's = increased IgE and IgA with decreased IgM

Front 96

Recurrent bacterial infections without pus and delayed separation of the umbilicus.

Back 96

Leukocyte adhesion deficiency type I = defect in LFA-1 integrin (CD18) on phagocytes = neutrophilia since they can't exit circulation

Front 97

Recurrent pyogenic infections by staph and strep with partial albinism and peripheral neuropathy

Back 97

Chediak-Higashi syndrome = AR defect in microtubulal function (LYST gene) = decreased phagocytosis with giant cytoplasmic granules in PMNs due to defective lysosomes

Front 98

Increased susceptability to catalase positive organisms like staph, ecoli, aspergillis, klebsiella, candida, pseudamonas, nocardia, and serratia

Back 98

Chronic granulomatous disease - XR lack of NADPH oxidase - decrease in reactive oxygen species and no PMN respiratory burst. Will see negative nirtoblue tetrazolium dye reduction test.
Tx prophylactically with TMP-SMX or INFgamma