Genetic Counseling Boards summary study guide verified 100%

Genetic Counseling Boards summary study guide verified 100% *Sickle Cell* Genetics Phenotype Diagnosis Treatment - *Genetics:* HbSS Gluexon6Val mutation in HBB gene chr. 11p15.4 *Phenotype:* Structurally abnormal Hb Manifests at 6-12 months (HbF -- HbA) Painful crises, anemia, organ damage, pulmonary HTN *Diagnosis:* Hb electrophoresis *Treatment:* hydroxyurea (stimulates HbF) *Alpha-thalassemia* Genetics Phenotype - *Genetics:* 2 alpha globin genes (4 alleles) chr. 16 *Phenotype:* aa/ao = silent carrier alpha-thal Heme healthy, occasionally low RBC indices ao/ao, aa/oo = alpha-thal trait mild anemia, low RBC indices oo/ao = HbH (B-chain tetramers -- "Heinz bodies" mild to moderately severe anemia, splenomegaly, icterus, abnormal RBC indices oo/oo = alpha-thal major severe, hydrops fetalis, incompat. with life *B-thalassemia* Genetics Phenotype - *Genetics:* B-globin gene chr. 11 *Phenotype:* B+ = silent B-thal carrier mild, no symptoms B- = B-thal trait mild anemia, abnormal RBC indices (Hb electrophoresis = elevated HbA2, HbF, or both) B+/B- = B-thal intermedia moderately severe anemia no transfusions needed B-/B- = B-thal major (Cooley's anemia) transfusion dependent anemia massive splenomegaly bone deformities 80% die 5 years *Hemoglobinopathies - General* Properties of Hb Phenotype - *Hemoglobin* HbF = alpha2/gamma2 = fetal HbA = alpha2/beta2 = primary adult HbA2 = alpha2/delta2= secondary adult alpha/non-alpha pair 1:1 excess of the normally produced globin destroys cell excess alpha global more toxic than excess beta globin *Phenotype* Sickle Cell = structurally abnormal hemoglobin Thalassemia = reduced quantity of hemoglobin *Meiosis I* - Reductional (2n -- n) 2n = 46, each chromosome with 2 sister chromatids *Stages of Meiosis I* - *Interphase* DNA replicates - 46 chromosomes, 2 sister chromatids *Prophase* chromatin condenses - *chiasmata/crossing over* *Metaphase* spindle attaches to centromere -- centrosomes move to poles *Anaphase* homologous chromosomes pulled apart *nondysjunction* can occur (homologous chr. pairs) *Meiosis II* - Equitational (n -- n) n = 23 2 daughter cells - 23 chromosomes/sister chromatids *Stages of Meiosis II* - *Prophase* *Metaphase* *Anaphase* sister chromatids separate *nondysjunction* can occur (sister chromatids) *Fatty Acid Oxidation* - 1. adipose fat stores 2. produce long chain fatty ACYL CoA (metabolite of fat) in the liver 3. long chain fatty ACYL CoA need to move from the liver to the mitochondria 4. carnitine is required 5. once in the mitochondria, carnitine is cleaved off 6. starts as a 16C long chain fatty ACYL CoA 7. long chain B-oxidation enzymes have a particular affinity for long chain fats 8. generate 2C ketone bodies (long chain is now 14C long) 9. keep making 2C ketone bodies until fat becomes a medium chain fat 10. enzymes with an affinity for medium chain fats cleave off 2C ketone bodies 11. leave a short chain remnant 12. short chain specific enzymes complete the job of turning fat into a useable form of energy *FAOD* *MC*AD - *M*ost *C*ommon ACADM gene, AR Previously health -- hypoketotis hypoglycemia, lethargy, coma, seizures *FAOD* VLCAD - ACADVL gene, AR Severe early onset - cardiomyopathy, hepatomegaly Early childhood onset - hepatomegaly, no heart Adult onset - rhabodomyolosis, exercise intolerance Tx: high carb, low fat diet, avoid fasting and infection, MCT oil (medium and short chain FA don't need carnitine to enter mitochondria) *FAOD* Ketone Production - 1. long chain fatty acid defects more likely to have muscle issues (very few ketone bodies to use for energy) 2. short chain defects have more ketone bodies 3. low ketone production found in medium chain and longer chain defects 4. low ketone production found in carnitine transport disorders 5. short chain defects associated with significant ketosis *FAOD* Treatment of VLCAD, LCAD - 1. medium chain fat doesn't need carnitine to shuttle into mitochondria 2. can use artificially synthesized MCT oil 3. MCT oil can get into mitochondria to be used as energy for patients with long chain fatty acid oxidation defects *FAOD* Biochemical testing - Low carnitine High acylcarnitine +/- hyperammonia *LSD* Tay Sachs - HEXA, AR hexosaminidase A GM2 accumulates progressive neurodegeneration cherry red spot no hepatosplenomegaly *LSD* Niemann-Pick - AR sphingomyelinase sphingomyelin accumulates Type A: SMPD1 gene, 1% enzyme activity hepatosplenomegaly FTT regression lung disease cherry red spot Type B: SMPD1 gene, 10% enzyme activity onset mid-childhood Type A + thrombocytopenia short stature and delayed bone age Type C: NPC1, NPC2 genes, proteins move lipids ataxia can't move eyes vertically dystonia liver lung *LSD* Fabry - XL alpha-galactosidase ceramide accumulates Classic, severe = no enzyme activity Milder, late-onset = reduced activity acroparasthesias angiokeratomas corneal opacities GI progressive renal disease stroke, MI *LSD* Gaucher - *MOST COMMON LSD* GBA gene, AR glucocerebrosidase glucocerebrosi