INBORN ERRORS IN METABOLISM

Garrod (1908) i inborn disease of metabolism term - _= metabolic

disease = group =i -i- =--i disease = i- enzyme = = i- i
metabolic activity = -_ i= i- enzyme = = ii oi- i- DNA
--- -- i- i- DNA =i --- protein = ii- ii = =i-i i-i
=i- mutant gene _= : -- : transmit = i- - iii=
inborn error of metabolism i i-i --- = ~i gene i =-i
ii- protein =i ii ---- DNA = -sZi i-i =i- --
ii- protein = harmful effects ~i i =- i- ~i - ii- protein _= enzyme
protein -i --=-i = i ~i -ii --i - -i=i- gene iii --- - iii
ii- i -i i enzyme = = i =- =o -iii = metabolism coci i-
o -= = inborn error of metabolism i- i -= - -i- i =- =i i

[A] Disorder of carbohydrate metabolism =>
1. Heriditary fructosaemia: - Liver =i enzyme fructose-1-phosphate aldolase, fructose-1-
phosphate =i -ic=- = i i-i =--i --- - gene - i i -i
homologous condition autosomal recessive - i i- = =i-i fructose-1-
phosphate =i i i i-i blood i-i i = i -- i i-i ii
_= - enzyme phosphoglucomutase = activity =i -- =- - -i =i-i
i=-i c - glycogen =i glucose glycogenolysis i i-i hypoglycemia i
i-i
2. Galactosuria: - Enzyme galactokinase i-- galactose = glucose -- =i ---
=--i Galactokinase galactose-1-phosphate uridyl transferase = - i-- galactose
=i i i i-i - blood urine galactose = ii o: i- i -
= ii -- =i i-i Galactose-1-phosphate = i-- i i i-- toxic effect
-- i-i i liver, kidney brain = -_ harmful i-i
3. Von Girkes disease: - genes autosomal recessive mutation = =i-i - glucose-6-
phosphate enzyme -i i -i -- glycogen glucose oii i =-i --- glucose
glycogen o =-i =i-i i-- glycogen i i i-i glycogen storage disease
~i =- _ -ii = ~ii = =o i- oi- blood glucose = ii i- i- +i= liver
glycogenolysis i-i i- -- ii i --i = =i-i ketosis fatty
liver -ii hyperlypemia i i i- disease =i 6 classes =- =i i
(a) Hepatic Renal Glycogenesis: - disease liver and kidney glucose-6-phosphate = =
-- i-
(b) Generalised Glycogenesis: - lysosome enzyme -1,4-glucosidase enzyme = =
i-i enzyme glycogen glucose ii =i - =--i glycogen = conc. o:
i- i- Cells - i i-
(c) Limit Dexitrinoses: - disease enzyme amylo-1,6-glucosidase = = i-i i
polysaccharides = ii-i- i = hydrolysis - ----i i-i enzyme = =
phosphorylase action i i-i i- oi- ii-iii - glycogen = ii = i i-
(d) Amylopectinosis: - disease branching enzyme (amylo-1,4 1,6-transglucosylase) =
liver lencocytes = -- i- = = glycogen branching point = i i-
i = amylopectin i-i --i-i
(e) Meardles Syndrome: - disease muscles phosphorylase enzyme = = i-
- muscles = enzyme i =i= = -_ i - i i i-
(f) Fructosuria: - o- = ii i i-i congenital disorder Liver fructose-1-
phosphaldolase = = fructose = utilization =i pathway block i i-i +-
fructokinase = = i i- = urine = ii fructose =i - i --i
[B] Disorder of lipid metabolism =>
1. Gauchers disease: - _= =i- =i lipidesis cerebroside i= lipid reticulo
endothelial system i i i-i =i- = -ii glucocerebrosidase enzyme = -
i i-
2. Niemann Pick disease: - Brain white and grey matter i i- white matter =i
-i phospholipid sphingomyline - i-i - ~i ii i-i sphingomylinase i
lysosomal hydrolase i= enzyme = . ~ii- i-i -ii Niemann disease i
i- _= familial disease i _= : -- : inherited i- disease
enzyme = -- visceral organs s o ii sphengomyline o: i-i disease
iii - -i--i= i -
3. Hypercholesterolemia: - disease _= recessive gene = - i i i- i-
ii = process cholesterol feedback control =i =i =--i disease serum
cholesterol = ii ii- zs ii o: i- i- +- cholesterol estrified cholesterol
=i i- ii- i i-i
4. Betalipoproteinemia: - disease plasma -lipoprotein = density = i i- -
lipoprotein extensive demylineted nerve = ii ci i-i disease lipids =i iiii
= i-i ii- chylomicron =i ii i-i
[C] Disorder of protein metabolism =>
1. Phenyl ketonuria (PKU): - Phenyl alanine hydroxylase enzyme, phenyl alanine i= amino
acid =i tyrosine o---i enzyme = - autosomal recessive inheritance error
enzyme -- i -i i- i-- phenyl alanine =--i i --i = --+- ii
- amino acids = metabolism - ~i ~ii ci-- =i- = disease ii-- iii
i i-
2. Albunism: - Tyrisinase enzyme, tyrosine amino acid =i melanine o-- =i --- =--i
Melanine --i =i pigment = absence --i - i i- Melanine pigment -
i o-i-i --- albino patient = --i i - i- i -i = iris ~i =ii -- i
i-i - -ii =i - =ii i -- -i ---- gene = autosomal
recessiveness = =i-i i-
3. Tyrosinosis: - error --- -- i-i _= enzyme P-hydroxy phenyl pyruvic acid
oxidase = = i i- i tyrosine -- hydroxyl phenyl pyruvate =i homogentisic
acid o---i =i-i hydroxy phenyl pyruvate -- i-i
4. Aleaptonuria: - Homogentisic acid =i maley lacto acetic acid o-- = =i =i
homogentisic acid oxidase enzyme ai-i --- =i i-i enzyme = - ~ii--i =
=i-i homogentisic acid -- =i i-i -i ~i --- -- i-i
Phenyl alanine
Hydroxylase Phenyl ketonuria
Tyrosine

Hydroxy phenyl pyruvate Melanine
Oxidase Tyrisinosis Albunism
Homogentisic acid
Oxidase Aleaptonuria
Maley lacto acetic acid to citric acid cycle

Management of inborn errors =>
Metabolic error - genetic errors =i =i -i- -i - o-i
-i_ i = -_ --- =- oii =i - i - = - - ~i = -o
_ --- --i =- i i o- = -_ genetic counseling = -i--
i =-i -i_
~ii ii =i iii= -ii amino acid centesis i- i . ~i =i
i =-i -i = o-i = i - - - - =i- =i oi -ii - =i
i-i
~ii -ii = ii i-i - i- =i i- i-- i-i -i.
fructosemia = -i =i fructose +- ~ii -
- metabolic end i middle product i-- - i= i -i -ii =i -i
=-ii -i_ -i. critinism = -ii - thyroxine i=
=o ii iiii =i i -ii - =i ii -i_ +i= -iii =i o:i
=-
-ii =i - i-ii o-ii -i_ -i. albuno patient =i i Haemophilia -i
=i -i-
i= +- -i- =i i-- oi- =i-i -i_