High Yield Comlex: Biochem

Front 1

Pt presents with failure to thrive and megaloblastic anemia that does not improve with vit B12. There is increased orotic acid in the urine with no hyperammonemia.

Back 1

Orotic aciduria.

AR

inability to convert orotic acid to UMP in the de novo pyrimidine synthase pathway.

defect in either orotic acid phosphoribisyltransferase or orotidine 5' phosphate decarboxylase.

TX: oral uridine

Front 2

Pt present with severe immunodeficiency. You diagnose SCID. What is the deficient enzyme?

Back 2

Adenosine deaminase deficiency.

excess ATP and dATP feedsback on ribonucleotide reductase.

this leads to a decrease in DNA synthesis and thus lymphocyte count.

This is one of the major, but perhaps not the only cause of SCID.

Front 3

Kid presents chewing his upper lip. He is mentally retarded and suffers from gout and hyperurecemia. Dx?

Back 3

Lesch-Nyhan syndrome.

X-linked recessive

Defective purine salvage because of loss of HGPRT.

HGPRT converts hypoxanthine to IMP and guanine to GMP.

The result is hyperurecemia.

Front 4

These pts suffer from dry skin and have a huge risk of melanoma, so much so that they rarely expose themselves to the sun.

Back 4

Xeroderma pigmentosum

There is a problem with endonucleases that prevent the repair of thymine dimers.

Front 5

Pt presents with course facial features, clouded corneas, restricted joint movements, and high levels of plasma lysosomes. Dx?

Back 5

I-Cell disease

Inherited lysosomal storage disease.

failure of addition of mannose-6-phosphate to lysosome, so enzymes are secreted outside the cell, rather than being targeted to the lysosome.

Front 6

Pt presents with yet another pyogenic infection...their 3rd this year. You notice there is partial albinism developing, and the pt mentions peripheral neuropathy. Dx?

Back 6

Chediak-Higashi syndrome.

microtubule defect resulting in decreased phagocytosis, leading to the symptoms.

Front 7

What drugs act on the microtubules?

Back 7

mebendazole/thiabendazole (antihelminthic)

Griseofulvin (antifungal)

vincristine/vinblastine (anti-cancer)

Paclitaxel (anti-breast ca)

colchicine (anti-gout)

Front 8

Differentiate between the 4 different types of collagen

Back 8

Type 1: bone, skin, dentin, tendon, cornea, late wound repair (STRONG)

Type 2: cartilage, vitreous body, nucleus pulposus (SLIPPERY)

Type 3: reticulin-skin, blood vessels, uterus, fetal tissue, granulation tissue (BLOODY)

Type 4: basement membrane or basal lamina (BM)

A STRONG, SLIPPERY, BLOODY, BM

Front 9

A patient with hyperextensible skin, hypermobile joints. The patient has several bruises. You Dx Ehlers-Danlos. What collagen is affected?

Back 9

Type III, most frequently.

ED has variable inheritance.

Associated with joint dislocation, berry aneurysms, and organ rupture.

Front 10

What are the symptoms and pathology of Alport's syndrome?

Back 10

Gene defects resulting in abnormal type IV collagen.

Results in progressive hereditary nephritis and deafness.

May also be associated with ocular disturbances.

CAN'T SEE, CAN'T PEE, CAN'T HEAR ME

Front 11

Describe the targets and probes of blotting techniques.

Back 11

Southern Blot: DNA. Probe: DNA

Northern Blot: RNA. Probe: DNA

Western Blot: Protein. Probe: Antibody

Front 12

What is the best study for detecting a single nucleotide polymorphism?

Back 12

Microarray!

Front 13

Define pleiotropy

Back 13

One gene has multiple effect in a phenotype.

Example: PKU causes a variety of symptoms, ranging from MR, to hair changes, to musty odor.

Front 14

Define imprinting

Back 14

Different phenotype depending on maternal or paternal inheritance.

Ex: Angelmann's in deletion on mom's chromo 15, Prader-Willi is dad's.

Front 15

What is the genetic problem in achondroplasia?

Back 15

defect of fibroblast growth factor receptor 3.

May be associated with advanced paternal age.

Front 16

Blood smear shows spheroid erythrocytes and increased MCHC. The patient has a history of hemolytic anemia. You diagnose hereditary spherocytosis. How do you treat?

Back 16

Splenectomy.

The spherical RBC are due to spectrin or ankyrin defect.

Front 17

What are the findings in neurofibromatosis type I, AKA von Recklinghausen's disease?

Back 17

cafe-au-lait spots, neural tumors, and Lisch nodules (pigmented hamartomas of iris).

AD inheritance.

There will also be scoliosis and optic pathway gliomas.

On chromo 17, long arm.

Front 18

Hemangioblastomas of retina, cerebellum, medulla.

Multiple bilateral renal cell carcinomas.

Dx?

Back 18

von Hippel-Lindau syndrome.

AD inheritance.

Associated with deletion of VHL gene on chromo 3p.

this leads to constitutive expression of HIF transcription factor and activation of angiogenic growth factors.

Front 19

What is the mutation in Duchenne's muscular dystrophy?

Back 19

X-linked frame shift deletion of the dystrophin gene.

This accelerates muscle breakdown and weakness.

Front 20

A 10 y/o boy presents with obvious MR. He has macrorchidism, a long face with a large jaw, and hypersensitivity to physical stimuli. Heart auscultation reveals a mid-systolic click heard best at the apex. Dx?

Back 20

Fragile X syndrome.

X-linked defect.

Numerous CGG repeats leading to methylation and silencing of the FMR1 gene.

Note that this is the 2nd most common cause of GENETIC MR, after Down's.

Front 21

What is the trinucleotide repeat in Huntington's?

Back 21

CAG

Front 22

What is the trinucleotide repeat in Myotonic dystrophy?

Back 22

CTG

Front 23

What is the trinucleotide repeat in Fragile X?

Back 23

CGG

Front 24

What is the trinucleotide repeat in Friedrich's ataxia?

Back 24

GAA

Front 25

A pregnant woman in her 2nd trimester has a quad screen. There is increased AFP and inhibin A, and decreased BhCG and estriol. Dx?

Back 25

Down's

Also look for translucency by nuchal line on US

Front 26

A pregnant woman in her 2nd trimester has a tri screen. AFP, estradiol, and BhCG are all decreased. Dx?

Back 26

Edwards, or trisomy 18.

Distinctive for clenched hands, rocker bottom feet, and micrognathia (small jaw)

Front 27

Describe a Robertson translocation.

Back 27

When two chromosomes with centromeres near the end fuse and the 2 short arms are lost.

Balanced translocations are not an issue, but unbalanced can lead to stillbirth, miscarriage, and chromo imbalance (Down's, Edwards).

Most common chromos are 13, 14, 15, 21, 22.

Front 28

Mutation involved with cri-du-chat?

Back 28

Microdeletion of the short arm of chromo 5.

Microcephaly, high pitched mewling, that creepy pic Thatcher put up.

Front 29

Pt presents with elfin facies, well developed verbal skills, and an outgoing personality. What do you suspect?

Back 29

Williams syndrome.

Deletion of the long arm of chromo 7.

Pts also suffer from hypercalcemia (due to increased sensitivity to vit D) and heart problems.

Front 30

An embryo has failure of development of the 3rd and 4th branchial pouches. What can they look forward to?

Back 30

There was a microdeletion at 22q11.

There will be CATCH 22 symptomes.

Cleft lip, abnormal facies, thymic aplasia, cardiac defects, hypercalcemia.

DiGeorge syndrome has thymic, parathyroid, and cardiac defects.

Velocardiofacial syndrome has palate, facial, and cardiac defects.