(2) 1.genetic disorders & inborn errors of metabolism

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GeneticGenetic

Disorders & Disorders &

Inborn ErrorsInborn Errorsof Metabolismof Metabolismpd f Mach ine - i s a pdf w r i te r t ha t pr oduces qua l i ty PDF f i l es w i t h ease!

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Categories of GeneticCategories of Genetic

DisordersDisorders

1.1. Chromosomal disordersChromosomal disorders

2.2. Monogenic disordersMonogenic disorders3.3. MultifactorialMultifactorial disordersdisorders

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DisordersDisorders1.1. Chromosomal disordersChromosomal disorders – –

Includes conditions in which there isIncludes conditions in which there is

excess loss of chromosomes, deletion of aexcess loss of chromosomes, deletion of apart of chromosome or translocationpart of chromosome or translocation

Can be recognized by analysis of theCan be recognized by analysis of the

karyotypekaryotype (chromosomal pattern) of an(chromosomal pattern) of an

individualindividual

E.g.E.g. TrisomyTrisomy 21 (Down21 (Down’ ’ s Syndrome)s Syndrome)













DisordersDisorders

2.2. Monogenic disordersMonogenic disorders – –

Involves single mutant geneInvolves single mutant gene Classified asClassified as – –

a.a. Autosomal Autosomal dominantdominant

b.b. Autosomal Autosomal recessiverecessivec.c. XX--linkedlinked













DisordersDisorders

3.3. MultifactorialMultifactorial disordersdisorders – –

Involves no. of genesInvolves no. of genes Pattern of inheritance of thesePattern of inheritance of these

conditions does not conform toconditions does not conform to

classicclassic MendelianMendelian genetic principlegenetic principle

E.g. common adult diseases like IHDE.g. common adult diseases like IHD

& HT& HT












Inborn Errors of Inborn Errors of

MetabolismMetabolism – – A Definition A Definition ‘ ‘ A mutation in a structural gene may affect the A mutation in a structural gene may affect the

structure of the encoded protein. If anstructure of the encoded protein. If an

enzyme is affected anenzyme is affected an inborn error of inborn error of metabolismmetabolism may resultmay result’ ’

‘ ‘Inborn Error of MetabolismInborn Error of Metabolism is a geneticis a genetic

disorder in which a specific enzyme isdisorder in which a specific enzyme isaffected, producing a metabolic block, whichaffected, producing a metabolic block, whichmay have pathological consequences.may have pathological consequences.’ ’ E.g.E.g.PKU,PKU, CystinuriaCystinuria,, PentosuriaPentosuria, Albinism etc., Albinism etc.












Patterns of InheritancePatterns of Inheritance Inheritance characteristics of an individual are determined by aInheritance characteristics of an individual are determined by aboutbout

50,000 gene pairs arranged on 23 pairs of chromosomes, one of 50,000 gene pairs arranged on 23 pairs of chromosomes, one of each pair coming from father & one from mother.each pair coming from father & one from mother.

Out of 23 pairs of chromosomesOut of 23 pairs of chromosomes

22 pairs determine 1 pair deter22 pairs determine 1 pair determinesmines

characteristics of sex of ancharacteristics of sex of an individualindividual

body cellsbody cells

Autosomes Autosomes Sex ChromosomesSex Chromosomes (X & Y)(X & Y)

Chromosome of each Female has 2X chromosoChromosome of each Female has 2X chromosomes (XX)mes (XX)

autosomeautosome pair are & male have one X & onepair are & male have one X & one Y Y

homologoushomologous












Patterns of InheritancePatterns of InheritanceDuring development of male & female reproductive cellsDuring development of male & female reproductive cells

Meiosis occursMeiosis occurs

SpermSperm OvumOvum

2222 Autosomes Autosomes + 22+ 22 Autosomes Autosomes ++

X or Y chromosomeX or Y chromosome X chromosomeX chromosome

FertilizationFertilization

Diploid Cell (46 chromosomes)Diploid Cell (46 chromosomes)












Autosomal Autosomal DisordersDisorders

‘ ‘If an inherited disease is caused by aIf an inherited disease is caused by a

mutant (abnormal) gene situated onmutant (abnormal) gene situated on

anan autosomeautosome, the disorder is called, the disorder is called

autosomalautosomal’ ’

It may be dominant or recessiveIt may be dominant or recessive












1.1. Autosomal Autosomal DominantDominant

DisorderDisorder

Presence of one mutant gene isPresence of one mutant gene is

necessary for the trait to benecessary for the trait to be

manifested in the carrier.manifested in the carrier.

E.g.E.g. HbpathiesHbpathies like SCA like SCA

HereditaryHereditary spherocytosisspherocytosis & &

Acute Acute intermittantintermittant porphyriaporphyria












1.1. Autosomal Autosomal DominantDominant

DisorderDisorder












2.2. Autosomal Autosomal RecessiveRecessive

DisorderDisorder

Disease is manifested only inDisease is manifested only in

homozygous (presence of 2 mutanthomozygous (presence of 2 mutant

genes)genes)

E.g. Cystic fibrosisE.g. Cystic fibrosis

PKUPKU

GalactosemiaGalactosemia












1.1. Autosomal Autosomal RecessiveRecessive

DisorderDisorder












Sex Linked DisorderSex Linked Disorder Most of the sexMost of the sex--linked disorders are carried on Xlinked disorders are carried on X--

chrchr

Females have 2 XFemales have 2 X

--chrchr

but only one of them is activebut only one of them is active

A women with one X A women with one X--chrchr carrying a recessivecarrying a recessivedisorder is unaffected clinically (Carrier)disorder is unaffected clinically (Carrier)

Homozygous female will however show the disorderHomozygous female will however show the disorder

Males have only one XMales have only one X--chrchr & this is always active. A & this is always active. A

male carrying recessive gene is therefore alwaysmale carrying recessive gene is therefore alwaysaffected clinicallyaffected clinically

E.g. GE.g. G--66--PD deficiency, Hemophilia, etc.PD deficiency, Hemophilia, etc.












Sex Linked DisorderSex Linked Disorder












Clinical Importance of Clinical Importance of

Inborn Errors of MetabolismInborn Errors of Metabolism DiagnosisDiagnosis

Prevent these conditions by geneticPrevent these conditions by genetic

counselingcounseling Prenatal diagnosis during subsequentPrenatal diagnosis during subsequent

pregnancies can help terminate thepregnancies can help terminate thepregnancy or plan apt place & plan forpregnancy or plan apt place & plan fordeliverydelivery

Recognition in early infancy of diseases likeRecognition in early infancy of diseases likeGalactosemiaGalactosemia, PKU, MSUD may prevent, PKU, MSUD may preventirreversible clinical consequences or deathirreversible clinical consequences or death












Clinical Importance of Clinical Importance of

Inborn Errors of MetabolismInborn Errors of Metabolism Blood relatives of affected patients shouldBlood relatives of affected patients should

screen themselves for Gscreen themselves for G--66--PD deficiency,PD deficiency,Familial hypercholesterolemia,Familial hypercholesterolemia, cystinuriacystinuria,,WilsonWilson’ ’ s diseases disease

Following inherited disorders can beFollowing inherited disorders can betreated symptomaticallytreated symptomatically – – congenitalcongenitaldisaccharidasedisaccharidase deficiency, hereditarydeficiency, hereditarynephrogenicnephrogenic diabetesdiabetes insipidusinsipidus

Following inborn errors are almostFollowing inborn errors are almostcompletely harmlesscompletely harmless – – renalrenal glycosuriaglycosuria,,GilbertGilbert’ ’ s diseases disease










(2) 1.genetic disorders & inborn errors of metabolism

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