Genetics

*Non-sense>Premature termination of protein synthesis>No Bglobin chain thus HemA(a2B2) is decreased>Increase in Hem A2(a2D2) and HemF(A2Y2)

*Don't get all wet if you see Glutamic acid substitution by Valine as this is RESULT of Missense(Point mutation that changes amino acid) mutation which involves Adenine Substitution by Thymidine.

*CF involves NON_frameshift mutation(Thus doesn't alter reading frame, our DNA is read in multiples of 3 so if you insert or delete something that is not Multiple of 3 you fck up whole reading frame)This non frameshift mutation results in addition of Amino acids or deletion because 3 nucleotides code for 1 amino acid, that is the case with CF-Deletion of Phenylalanine from CFTR>CFTR can't reach cell surface and is degraded in golgi.*Tay sachs which is also inherited in AR pattern(Like CF) involves frameshif mutation because there is 4 nucleotide insertion(Not multiple of 3)>Reading frame is displaced>Hexosaminidase deficiency>Accumulation GM2.*Note: insertion in tay-sachs is TATC.If you ever wondered CHerry red macula is due to pale ganglion cells with too much ganglicoides accentuating Natural color of choroid(Middle layer, between inner retina and fibrous outer covering)

*CGG is amplificated during Oogenesis(X-linked dominant disorder called Fragile X syndrome-Macroorchidism+Mental retardation)*CAG amplification happens during Spermatogenesis(Huntigton's disease -Autosomal Dominant disease>Caudate nucleus atrophy on MRI)*Number of triplet repeats is of prognostic value and increase in triplet numbers>Worse prognosis(Anticipation-increase in number of triplets>earlier onset of more severe symptoms with each generation)

*CTG repeat on chromosome 19>Myotonic dystrophy(AD)>can die from arythmia,this disease loves to destroy Type1 fibers+likes to make you bald+Testicular atrophy+They have sustained grip(Remember they Sustain their grip till their balls atrophy-I KNOW IM LAME but it helps)*GAA repeat on chromosome 9 >Friedreich ataxia<Likely to die from Hypertrophic cardiomyopathy(Which is normally due to mutation in Bmyosin heavy chain that has AD inheritance but here Friedreich ataxia has AR inheritance, but here problem is in mitochondria due to repeats in frataxin gene>Less frataxin-remember Noncoding regions=INtrons are amplified>Less protein snthesis(Other examples of NONcoding region=intron amplification>less protein are Myotonic dystrophy,FXS)*CAG repeat involves amplificationin EXons(Coding regions) that code for Glutamine residues>Polyglutamine disorders(HD and Spinocerebellar ataxia<Also can be caused by Intron amplification in Friedreich's ataxia)

*C1 esterase inhibitor deficiency but everyone knows that so remember that is is inherited in Autosomal Dominant pattern.

*Note as disease is AR you also know Chance of having child with AR condition(1/4)Prevalence=Chance of having Child with AR conditionXNumber of couples at risk(if carrier state is 1/100 that couples at risk are 1/10000 because both of them should be carriers)=1/4 X 1/10000*Thus If you knew prevalence you could divide it by 4 to get Number of couples at risk.*Square root from number of couples at risk would give you information about carrier state.(Remember we squared chance of being carrier to get the number of couples at risk)

*GALT is deficient so GALT can't take Galactose 1 p and give you UDP galactose.(So Galactose 1 p Increases while Glucose 1 p decreases because UDP galactose is not made )*For now remember that inheritance is Autosomal recessive(Enzyme deficiencies are mostly AR)*Osmotic damage to lens is due to Galactitol accumulation which drives fluid into it.*Increased risk of Neonatal Sepsis due to decreased leukocyte bactericidal effect.

*Maleyacetoacetate is actually Decreased because Homogentisatte oxidase is lacking(AR) which now can't metabolize Homogentisate to maleyacetoacetate(Too much HOMOGENTISATE is responsible for black discolorations and degenerative arthritis.*Homogentisate Oxidase deficiency>Alkaptonuria which is Autosomal recessive condition(This is what our patient has).*Homogenistic acid oxidation when exposed to light>Pigmentation of urine

*Cirrhosis is due to accumulation of Fructose 1 phopshate(Aldolase B is deficient in this AR condition so you can't convert Fructose1P>G3pand DHAP=Hypoglycemia due to lack of gluconeogenic sybstate while Fructose 1p accumulates >Used up phosphate >Hypophosphatemia)Remember to not give Honey(Fructose) and Sucrose(Glucose+Fructose).FOR NOW at least remember it is Autosomal Recessive(remember enzyme def. is most likely AR)

*Autosomal recessive(Maple Syrup urine disease)*Lack of Branched chain a-ketoacid deh. >Accumulation of Isoleucine,Leucine,ValineJust remember these 3 they might throw AcCoa,Succinyl CoA or something but remember they are likely to be decreased if you understand why that is awesome and that is more of biochemistry but if you can't your best shot would be that everything except these 3 AA's will be decreased.*we will repeat all these diseases in Biochemistry

*BOTH of them are Autosomal recessive but different enzymes are lacking*In Phenylketonuria you lack Phenylalaninehydroxylase>increased phenylalanine+Decreased tyrosine but in Malignant phenylketonuria u lack Dihydropteritin Reducase needed for BH4 synthesis which is needed for Tryptophan and tyrosine metabolism to Serotonin and Dopamine respectively.You are lucky if they ask you inheritance because both of them are AR.*If Restriction in phenylalanine doesn't help with symptoms it is likely Malignant Phenylketonuria.(You need to give BH4+Ldopa+5 hydroxytryptophan)*Remember PHenylacids are responsible for mousy odor and decrease in tyrosine is responsible for decreased pigmentation in Phenylketonuria(Melanin comes from it)*Excess Phenylalanine is responsible for mental rtardation

*Autosomal recessive lack of Galactokinase(can't convert galactose to galactose 1p)even if you weren't sure if it was this or Galactosemia(Lack of GALT) answer would still be Aurosomal recessive :)) as GALT(can't convert G1p>UDB glucose) deficiency is also inherited in Autosomal recessive fation.

*McArdle disease(Type5)-Glycogen phosphorylase lack>Rhabdomyolisis with myoglobinuria with NO lactic acid increase with excercise(Lack of glucose because glycogen can't be posphorylated>too much glycogen in muscle)*Pompe Disease(Type 2)-Alpha1,4 glucosidase=Acid maltase(LYSOSOMAL ENZYME) >Increased glycogen and Cardiomegaly, most likely cause of death:RESTRICTIVE cardiomyopathy.*Von Gierke(type1)-Too much Glucose6phosphate due to lack of Glucose6phosphatASE so less g6p is converted to glucose(So Fasting hypoglycemia with Enlarged KIDNEY and Liver as both are involved in gluconecogenesis)*Cori disease(type3)-Debranching eznyme(1,6glucosidase def)<too much glycogen,Limit dextrins in cytosol.EY FOR NOW AT LEAST KNOW That they are AR, we will go into details with biochem.

*Autosomal recessive fation these all can cause homocystinuria- Patietns have marfanoid habitus which is example of Genetic heterogenneity.