Biochemistry 17 - Inborn Errors Of Metabolism

Front 1

What are the classes of metabolic disorders

Back 1

1. Carbohydrate metabolism, 2. AA metabolism, 3. lipid metabolism 4. organic acid metabolism, 5. urea cycle metabolism, 6. energy production defects, 7. transport defects

Front 2

Classic galactosemia

Back 2

Galactose-1-phosphate uridyl transferase w/a missense mutation in exon 6 -> cannot convert galactose -> glucose efficiently -> galactose builds up -> cataracts (galactitol)

Front 3

New born w/failure to thrive, hepatic insufficiency, cataraccts, developmental delay, poor growth and mental retardation

Back 3

Galactosemia - screen the child by checking blood for enzyme activity -> dietary restriction of galactose; defective GAL-1-P uridyl transferase

Front 4

Hereditary fructose intolerance

Back 4

Defect in fructose 1,6 bisphosphate aldolase -> Appears after adding fruit to diet; occurs in liver, kidney cortex and small intestine; KIDS AVOIDS FRUTS AND CANDY!!!

Front 5

New born w/poor feeding, failure to thrive, hepatic and renal insufficiency -> death. Infants who are breast-fed becomes symptomatic after weaning, when fruits and vegetables are added to their diet -> avoids foods that they consider noxious.

Back 5

Hereditary fructose intolerance (HFI) - defect in fructose-1,6- bisphosphate alodolase

Front 6

Von gierke disease

Back 6

Defect in glucose-6-phosphatase -> glycogen storage disorder; hepatomegaly and hypoglycemia

Front 7

Pt w/hepatomegaly and hypoglycemia. -> causes exercise intolerance -> progressive weakness -> cramping. Defect in glucose-6-phosphatase

Back 7

Von gierk disease- Type Ia glycogen storage disorder

Front 8

Phenylketonuria

Back 8

Defective phenylalanine hydroxylase gene (PAH) -> ↑ [phenylalanine] -> disrupts brain(myelination, protein synthesis) -> retardation

Front 9

Pt w/elevated lvels of plasma phenylalanine -> disrupts essential cellular processes in the brain (myelination and protein synthesis) -> resulting in severe mental retardation. Pt found to have mutated phenylalanine hydroxylase

Back 9

Phenylketonuria - treatment = dietary restriction of phenylalanine containing foods

Front 10

Who needs to be careful w/PKU?

Back 10

Pregant women w/PKU must be especially carful b/c ↑ [phenylalanine] in maternal blood lvls affect the fetus-> causes poor growth -> microcephaly -> mental retardation of the fetus. Thus women w/PKU and pregnant need low [phenylalanine] diet

Front 11

Maple syrup urine disease

Back 11

Cannot metabolize branched chain keotacids from branched chain amino acids -> ↑ [BCAA] -> leads to neurodegeneration -> death in months!!

Front 12

New born who diaper smells like maple syrup. And blood levels find an accumulation of branched chain amino acids -> leads to neruodegeneration and death in first few months.

Back 12

Maple syrup urine disease - defect in branched chain alpha-ketoacid dehydrogenase

Front 13

Medium-chain -acyl-coenzyme A dehydrogenase deficiency (MCAD)

Back 13

FA metabolism defect -> gets hypoglycemic after fasting -> vomits and lethargy after a minor illness (upper respirator/GI) -> ↑ [fatty acid intermediates] -> insufficient ketone bodies -> ↓ glycogen!!

Front 14

Child w/ vomiting and lethargy after a period of diminished oral intake due to a minor illness(ie upper respiratory illness, gastroenteritis). Fasting results in the accumulation of fatty acid intermediates, a failure ot produce ketones in sufficient quantities to meet tissue demands-> exhaust glucose supplies -> cerebral edema -> encephalopathy -> death.

Back 14

Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency

Front 15

What is the treatment of MCAD?

Back 15

Avoid fasting!! b/c u cant use ur energy stores

Front 16

What is bad about MCAD?

Back 16

Cerebral edema -> exhustion of glucose supplies -> death (in northwestern europeans)

Front 17

What is the mutation in MCAD?

Back 17

Single missense A -> G (lysine -> glutamate)

Front 18

Congenital adrenal hyperplasia

Back 18

Block in corticosteroid synthesis -> virilization of females in uteros -> severe forms cause salt-wasting (weight loss, lethargy, dehydration, death)

Front 19

Zellwegger syndrome

Back 19

Peroxisome biogenesis disorder

Front 20

Neonatal hypotonia, progressive white matter disease, distinctive face, death in infancy

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Zellwegger syndrome

Front 21

Lysosomal storage disorders

Back 21

Accumulation of Mucopolysaccharides, sphingolipids, glycopriteins, glycolidis b/c its not degraded

Front 22

What are defective in mucopolysaccharidoses

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Heparin sulfate, dermatan sulfate, keratan sulfate, chondroitin sulfate

Front 23

Pt w/ progressive multisystem deterioration-> hearing , vision, joint, and cardiovascular dysfunction

Back 23

Mucopolysaccharidoses (MPS) disorder

Front 24

A boy w/a mutation in alpha-I-iduronidase. Boy has coarse facial features, crouched stance, thickened digits, and protuberant abdomen.

Back 24

Hurler syndrome - a type of mucopolysaccharidoses disorder

Front 25

Sphingolipidoses diseases

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1. Gaucher(glucosidase deficiency), 2. tay-sachs(hexosaminidase A deficiency), 3. niemann-pick(sphingomyelinase deficiency)

Front 26

Pt w/splenomegaly, hepatomegaly, bone marrow infiltration, brain usually spared. Defect in beta-glucosidease.

Back 26

Gaucher

Front 27

Hypotonia, spasticity, seizures, blindness. Defect in hexosaminidase A

Back 27

Tay-sachs

Front 28

Hepatomegaly, corneal opacities, brain deterioation. Defect in sphingomyelinase.

Back 28

Niemann-pick

Front 29

Pt w/microscopic examination of tissues finds inclusions. Inclusions contain partially degraded oligosaccharides, lipids, and glycosamnioglycans. Defect in mannose-6-P + phosphotransferase

Back 29

I-cell disease

Front 30

Pt w/progressive lethargy and coma. Accumulation of ornithine in the urine

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Ornithine transcarbamylase (OTC) - treatment = prevent hyperammonemia from excess nitrogen

Front 31

Pt w/ defect of dibasic amino acid transport affeting the epitheilal cells of the gastrointestianl tract and renal tubules -> ↑ urinary [cystine], [lysine], [arginine], [ornithine] -> formation of kidney stones.

Back 31

Cystinuria

Front 32

Cystinuria Type I defect

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SLC3A1

Front 33

Cystinuria Type II + III defect

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SLC7A9

Front 34

Pt w/defective transporter for lysosomes w/ cystine crystals in them. Normal at birh but develop electrolyte disturbances, corneal crystals, rickeets, and poor growth by the age of 1 yo

Back 34

Cystinosis

Front 35

Pt w/defect in copper excretion to biliary tract -> progressive liver disease, dysarthria, diminished coordiantion, arthropathy, cardiomyopathy, kidney damage, hypoparathyroidism, kayser-fleisher ring in the eye

Back 35

Wilsons disease - defective ATP7B

Front 36

Pt w/excessive iron absorption in the small intestine -> Fe accumulates in liver, kidney, heart, joints and pancrease -> fatigue, diminished libido, diabetes, ↑ skin pigmentation, cardiomyopathy, liver enlargement and cirrhosis

Back 36

Hereditary hemochromatosis (HH) - example of incomplete penetrance - Linkage to HLA region

Front 37

What is the treatment for hemochromatosis?

Back 37

Blood letting

Front 38

Genetic heterogeneity

Back 38

Indistinguishable phenotypes may be produced by mutations in different genes