Inborn errors of metabolism Flashcards by Toni Henry

G6PD deficiency has a higher incidence rate in individuals from ___, ___, ___, and ___

Africa
Asia
Mediterranean (Sardinian descent)
Middle East

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G6PD follows ____ inheritance pattern

X linked recessive

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results from mutations in the glucose 6 phosphate dehydrogenase enzyme

glucose 6 phosphate dehydrogenase deficiency

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G6PD deficiency leads to the inability to form ____ and the accumulation of ____

NADPH
ROS

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G6PD deficiency may lead to ____

hemolysis

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_____ have high levels of vicine and convicine that are high in oxidative stressors therefore people with G6PD deficiency cannot eat these.

fava beans

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G6PD deficiency impairs the ability of an erythrocyte to form ____ resulting in ____

NADPH
hemolysis

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disease is due to a deficiency in methylmalonyl CoA mutase of adenosylcobalamin

methlymalonic acidemia

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methylmalonic acidemia results in elevated levels of ____ (___) in the blood

methylmalonic acid
methylmalonate

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methylmalonic acidemia leads to ___ and ____

metabolic acidosis
developmental problems

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deficiency in branched chain a-keto acid dehydrogenase (BCKD)

maple syrup urine disease

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in maple syrup urine disease levels of ____ and their ___ analogs are elevated in plasma and urine

branched chain a-amino acids
a-keto analogs

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maple syrup urine disease leads to ____

neurologic problems (common)

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maple syrup urine disease has a ___ mortality rate

high

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treatment for maple syrup urine disease includes ___________

restricted dietary intake of the branched chain amino acids

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classic form is due to a deficiency in cystathionine synthase

homocystinuria

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homocystinuria results in an accumulation of ____ in the urine

homocysteine

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homocystinuria leads to elevated levels of ___ and ___ in the blood but ___ is low

methionine
homocysteine
cysteine

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homocystinuria results in ___, ____, ____, and ____

skeletal abnormalities
increased risk of clotting
lens dislocation
intellectual disability

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most commonly encountered inborn error of metabolism

phenylketonuria

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PKU follows ____ inheritance pattern

autosomal recessive

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results from a homozygous or compound heterozygous mutations in the phenylalanine hydroxylase enzyme

PKU

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PKU is clinically and biochemically characterized by _____

hyperphenylalanimia

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PKU leads to levels of phenylalanine that are __ higher in plasma, urine and body tissues relative to normal

10 times

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failure to treat PKU results in ____, ___, ___, and ___

intellectual disability developmental delays microcephaly seizures

treatment of PKU includes _____ along with ____

restriction of phenylalanine supplementation of tyrosine

treatment for PKU in essence, restricts the ___ for the enzymatic reaction and supplement with the ___ bypassing the necessity of the enzyme

substrate product

maple syrup urine disease follows ___ inheritance pattern

autosomal recessive

converts phenylalanine to tyrosine

phenylalanine hydroxylase

enzyme that oxidatively decarboxylates the branched chain amino acids leucine, isoleucine and valine

BCKD

maple syrup urine disease results in a build up of the ____ forms of leucine, isoleucine and valine in the blood causing a toxic effects that interferes with ____

a-keto acid brain function

maple syrup urine disease presents with ___, ___, ___, ___, ____ that may result in coma due to high levels of ___, ____ due to high levels of ___

feeding problems vomiting ketoacidosis changes in muscle tone neurologic problems leucine maple syrup smelling urine isoleucine

homocystinuria follows ___ inheritance pattern

autosomal recessive

results from mutations in the enzyme csytathione B-synthase

homocystinuria

converts homocysteine to cystathionine

cystathione B-synthase

homocystinuria results in a build up of ___ and ___ levels in the blood and urine with low levels of _____ in plasma

homocysteine methionine cysteine

homocystinuria presents with ___, ____, ____, and ____

dislocation of the lens skeletal abnormalities (long limbs and fingers) intellectual disability increased risk for developing thrombi

treatment for homocystinuria includes restriction of ___ and supplementation with ___ and ___

methionine vitamin B12 folate

methylmalonic acidemia follows ___ inheritance pattern

autosomal recessive

results from mutations in the enzyme methylmalonyl CoA mutase

methylmalonic acidemia

converts methylmalonyl CoA into succinyl CoA which then enters the TCA cycle

methylmalonyl CoA mutase

methylmalonic acidemia results in the inability to metabolize the amino acids ___, ____, ___, and ___

valine isoleucine threonine methionine

methylmalonic acidemia results in a build up of ____ (____) in the blood and urine

methylmalonic acid methylmalonate

clinical presentation of methylmalonic acidemia is ___, ___, ___, ___, ___, ___, and ____

vomiting dehydration hypotonia lethargy hepatomegaly feeding problems metabolic acidosis

alkaptonuria follows ___ inheritance pattern

autosomal recessive

results from mutations in the enzyme homogenistic acid oxidase

alkaptonuria

converts homogentisate into maleylacetoacetate in the tyrosine degradation pathway

homogentistic acid oxidase

alkaptonuria results in the inability to metabolize ____

tyrosine

alkaptonuria results in a build up of ____

homogentisic acid

alkaptonuria presents with ____, ____, ____

homogentisic aciduria (urine contains elevated levels of HA) early onset arthritis of the large joints deposition of black pigment in the cartilage and collagenous tissue

alkaptonuria is not life threatening and usually presents ____ but may have ____

later in life debilitating arthritis

albinism primarily follows ____ inheritance pattern

autosomal recessive

results from mutations in the copper requiring tyrosinase

type I albinism

catalyzes the first 2 steps in the synthesis of melanin from tyrosine

tyrosinase

albinism results in the inability to produce ____ thereby having an absence of ____

melanin pigmentation in the skin, hair and eyes

general clinical presentation of urea cycle deficiencies that results because the amount of ammonia generation in the system surpasses the capacity of the urea cycle to remove the ammonia

hyperammonemia

hyperammonemia is a medical emergency because ammonia has ____

neurotoxic effects on CNS

two types of hyperammonemia

acquired congenital

acquired hyperammonemia can result from ____

liver damage

most common urea cycle disorder

ornithine transcarbamylase deficiency

ornithine transcarbamylase deficiency follows ___ inheritance pattern

X-linked

results from mutations in the enzyme ornithine trascarbamylase

ornithine transcarbomylase deficiency

transfers a carbomoyl group from carbomoyl phosphate to ornithine to generate citrulline

ornithine trasncarbomylase

ornithine transcarbamylase deficiency results in the inability to ____

undergo early step in urea cycle

ornithine transcarbomylase deficiency presents with decrease in the levels of downstream products ___ and ___

citrulline arginine

ornithine transcarbomylase deficiency in neonates presents with ___, ___, ___

lethargy unwillingness to eat poorly controlled breathing rate and body temperature

treatment for ornithine transcarbomylase deficiency may consist of ___ and taking ___ and ___ supplements

low protein diet arginine citrulline

arininosuccinate lyase deficiency follows ___ inheritance pattern

autosomal recessive

results from mutation in the enzyme argininosuccinate lyase

arginiosuccinate lyase deficiency (argininesuccinate aciduria)

removes fumerate from argininosuccinate to generate arginine and fumerate

argininosuccinate lyase

arininosuccinate lyase deficiency results in the inability to undergo ___ step in urea cylce

3rd

arginiosuccinate lyase deficiency presents with ___, ___, ___

lethargy unwillingness to eat poorly controlled breathing rate and body temperature

argininosuccinate lyase deficiency results in increased ___ and ___ in the urine with decreased levels of ____

argininosuccinate citrulline arginine

argininosuccinate lyase deficiency treatment may consists of ___ and taking ___ supplement

low protein diet arginine

arginase I deficiency follows ___ inheritance pattern

autosomal recessive

results from mutation in the enzyme arginase I

arginase I deficiency (arginemia)

removes urea from arginine to produce ornithine which is then transported to the mitochondria and reenters the urea cycle

arginase I

arginemia results in the inability to undergo ___ step of the urea cycle

4th

arginemia results in build up of ___ and ___ in blood and urine

arginine ammonia

arginemia may appear normal development from __-__ years but after presents with ____, ___, and ____

1 3 loss of developmental milestones developmental delays intellectual disability

treatment for arginemia consists of ___, ___ and ___ supplement

low protein diet arginine restricted diet essential amino acid

n-acetylglutamate synthase deficiency follows ___ inheritance pattern

autosomal recessive

results from mutation in the enzyme n-acetylglutamate synthase

n-acetylglutamate synthase deficiency

combines acetyl CoA and glutamate to make NAG

NAG synthase

essential activator of carbomoyl phosphate synthetase I which combines bicarbonate and ammonia to enter the urea cycle

NAG

NAG synthase deficiency results in the inability to generate ___

NAG

NAG synthase deficiency appears ___ and presents with ___, ___, ____, ___, and ____

first few days of life lethargic unwilling to eat difficulty controlling breathing and temperature developmental delays intellectual diability

treatment for NAG synthase deficiency may consist of ___ with ___ supplements to enable the ability to make ___ for the urea cycle

low protein diet arginine ornithine

most common inherited cause of nonspherocytic hemolytic anemia

pyruvate kinase deficiency

PK deficiency follows ____ inheritance pattern

autosomal recessive

results from mutation in the enzyme PK the final enzyme in glycolysis

PK deficiency

transfers a phosphate group from phosphoenolpyruvate to ADP to generate a molecule of ATP and pyruvate

PK presents with ___, ___, ___, ___, ___, and ___

hemolytic anemia (moderate to severe) pale skin jaundice fatigue SOB rapid HR

entirely dependent on glycolysis for energy production

RBC

usually unaffected by PK deficiency due to the ability to generate ATP from oxidative phosphorylation in their mitochondria

liver cells

treatment for PK deficiency may consist of ___ supplementation to increase ____ and ____

folic acid RBC production hematopoietic stem cell transplantation

most common GSD

McArdle's Disease

McArdle's Disease follows ___ inheritance pattern

autosomal recessive

results from mutations in the enzyme muscle glycogen phosphorylase

McArdle's disease

removes glucose 1-P from glycogen

glycogen phosphorylase

McArdle's disease leads to the inability to ____

breakdown glycogen stores

McArdle's disease affects ___ and is a relatively ___ condition

skeletal muscle benign chronic

Von Gierke disease follows __ inheritance pattern

autosomal recessive

results from mutations in the enzyme glucose 6 phosphatase

Von Gierke disease

enzyme that removes a phosphate to generate free glucose

glucose 6 phosphatase

Von Gierke disease leads to inability to ______

utilize G6P released from glycogen breakdown as an energy source

12 clinical presentations of Von Gierke disease

fasting hypoglycemia fatty liver hepatomegaly renomegaly progressive renal disease growth retardation delayed puberty lactic acidemia HLD hyperuricemia increased glycogen stored normal glycogen structure

Type Ib GSD characterized by ___ and ___

neutropenia recurrent infection

treatment for Von Gierke Disease includes ____ or ____

nocturnal gastric infusions of glucose regular administration of uncooked cornstarch

Pompe's disease follows ___ inheritance pattern

autosomal recessive

the only glycogen storage disease that is also a lysosomal storage disorder

Pompe's disease

results from mutations in the enzyme a(1-4) glucosidase

pompe disease

releases a glucose form glycogen instead of B glucose

a(1-4) glucosidase

pompe's disease leads to the inability to _____

breakdown glycogen stores

pompe's disease leads to a build up of _____

toxic sugar levels in lysosomes

Pompey’s disease damages organs and tissues in particular ___

muscles

treatment for pompe's disease may consist of ___

enzyme replacement therapy

Cori's disease affects _____

North African Jewish ancestry

Cori's disease follows ___ inheritance pattern

autosomal recessive

results from mutations in the enzyme with two catalytic functions amylo-a(1-6) glucosidase 4-a-glucotransferase

Cori's disease

involved in the debranching of glycogen

amylo-a(1-6) glucosidase 4-a-glucotransferase

cori's disease leads to a build up of ___ and ____

abnormal glycogen partially broken down glycogen stores

cori's disease damages organs and tissue in particular ___ and ___

liver muscles

essential fructosuria follows ____ inheritance pattern

autosomal recessive

results from mutations in the fructokinase enzyme

essential fructosuria

adds a phosphate to fructose in the first step of fructose metabolism

fructokinase

essential fructosuria leads to the inability to ____ and build up of ___ in the urine

metabolize fructose fructose

essential fructosuria is a benign condition so if diagnosed then limit ____

fructose intake

HFI follows ___ inheritance pattern

autosomal recessive

results from mutations in the aldolase B enzyme

HFI

converts fructose 1P into glyceraldehyde and G3P

aldolase B

HFI leads to the inability to _____ and build up of ___

metabolize fructose fructose 1P

HFI treatment includes ____

replacement of other sugars for fructose

___, ___, and ___ can cause hepatic failure and death

fructose sucrose sorbitol

HFI presents with ___, ___, ___, ___, ___, ___, ___, and ___

severe hypoglycemia vomiting jaundice hemorrhage hepatomegaly renal dysfunction hyperuricemia lactic acidemia

classic galactosemia follows ___ inheritance pattern

autosomal recessive

results from mutations in the galactose 1 phosphate uridylyltransferase

classic galactosemia

converts galactose UDP to glucose UDP

GALT

classic galactosemia leads to inability to _____

convert galactose to a form usable for glycolysis and subsequent energy production

classic galactosemia causes ___ and ___

galactosemia galactosuria

classic galactosemia results in accumulation of ___ and ___ in the ___, ___, and ___ causing ___, ___, and ___

galactose 1P galactitol brain liver eyes liver damage brain damage cataracts

despite adequate treatment, patients with classic galactosemia are at risk for __, ___, and in females ____

cataracts developmental delays premature ovarian failure

galactokinase deficiency follows ___ inheritance pattern

autosomal recessive

results from mutations in the galactokinase enzyme

galactosemia type II (GALK deficiency)

converts galactose to galactose 1P

GALK

GALK deficiency leads to the inability to ____ the first step of galactose metabolism

phosphorylate galactose

GALK deficiency causes elevation of ___ in blood and in urine

galactose

GALK deficiency causes ___ accumulation if galactose is present in the diet

galactitol

Hurler disease follows ___ inheritance pattern

autosomal recessive

results from mutations in the enzyme a-L iduronidase

hurler disease

removes iduronic acid from GAGs

a-L iduronidase

hurler disease leads to a build up of ____ which increases the size of ___ within cells

GAGs in lysosomes lysosomes

hurler disease presents with ___, ___, ___, ___, ___, and ____

corneal clouding developmental disability dwarfing coarse facial features upper airway obstruction hearing loss

hurler disease can cause deposition in ___ leading to ___ and ___

coronary artery ischemia early death

hurler disease can be treated with ___ or ___ before 18 months

bone marrow transplant cord blood transplant

hunter disease follows ___ inheritance pattern

X linked

results from mutations in the enzyme iduronate 2 sulfatase gene

hunter disease

removes sulfur from iduronate acid present on GAGs

IDS

hunter disease leads to a build up of ____ which increases ___ within the cell

GAGs in lysosomes size of lysosomes

life expectancy of hunter disease is ____

10-20 years

hunter disease presents with ____ and ___

physical deformity (mild to severe) developmental disability

MCAD deficiency has a higher incidence rate in people of ____

Northern European descent

MCAD deficiency follows ___ inheritance pattern

autosomal recessive

family of enzymes that metabolize FA based on their length

acyl CoA dehydrogenases

acyl CoA dehydrogenase is the first step in ___ and introduces a ___ between the 2nd and 3rd carbon bond of the acyl CoA thioester substrate

beta oxidation trans double bond

acyl CoA dehydrogenase generates molecules of ___ which is used in oxidative phosphorylation

FADH

MCAD deficiency results in an inability to _____, decrease in ___ and greater reliance on ____

metabolize FA of 6-10 carbons in length acetyl CoA glucose for energy

MCAD deficiency presents with ___, ___, ___ and ___ state due to reliance of glucose and decrease in reliance on FA

vomiting lethargy hypoglycemic hypoketotic

MCAD deficiency results in accumulation of ___ and ___ in urine

medium chain acyl carnitines medium chain dicarboxylic acids

Tay Sachs disease has a higher incidence rate in ___, ___, ___, and ___

Ashkenazi Jewish Cajun French Canadian Pennsylvania Dutch

Tay Sachs follows ___ inheritance pattern

autosomal recessive

results from mutations in the lysosomal enzyme beta N acetylhexasomaminidase A (HEXA)

tay sachs disease

removes GalNAc from NANA

HEXA

tay sachs results in the inability to ____

hydrolyze Gm2 gangliosides

tay sachs results in the build up of ___

gangliosides

tay sachs presents with ____, ___, ___, ___, ___, and ___

rapid, progressive and fatal neurodegeneration blindness seizures excessive startle response muscle weakness cherry red macula

fabry disease follows ____ inheritance pattern

X-linked

results from mutations in the alpha galactosidase A enzyme (GLA)

fabry disease

degrades the molecule globotriasoylceramide

GLA

fabry disease results in the inability to ____

hydrolize globosides

fabry disease results in a build up of ____ in cells throughout the body

globotriaosylceramide

fabry disease presents with ___, ____, ___, and ___

red-purple skin rash kidney failure heart failure burning pain in LE

krabbe disease follows ___ inheritance pattern

autosomal recessive

results from mutations in the galactosylceramidase(GALC)

krabbe disease

degrades certain fats called galactosylceramides

GALC

krabbe disease results in the inability to ____ leading to a buildup of these molecules forming ____

degrade galactosylceramides globoid cells

krabbe disease impairs the formation of ___ and leads to ____

myelin dymelination in NS

krabbe disease presents with ___, ___, ___, ___, ___, and ____

mental deterioration motor deterioration blindless deafness near total loss of myelin globoid bodies in white matter of brain

gaucher disease has a higher incidence rate in ____

Ashkenazi Jewish herritage

gaucher disease follows ___ inheritance pattern

autosomal recessive

results from mutations in the enzyme beta glucosidase

gaucher disease

hydrolyzes the beta glucosidic linkage of the molecule glucocerebrodise

beta glucosidase

gaucher disease results in the inability to ____ leading to a buildup of these molecules

hydrolyze glucocerebroside

most common lysosomal storage disease

gaucher disease

guacher disease presents with ___ and ____

hepatosplenomegaly osteoporosis of long bones

niemann pick disease has a higher incidence rate in ____

Ashkenazi Jewish heritage

neimann pick follows __ inheritance pattern

autosomal recessive

results from mutations in the enzyme sphingomyelin phosphodiesterase 1 (SMPD1)

niemann pick disease

converts sphingomyelin into ceramide

SMPD1

niemann pick disease results in the inability to ____ leading to a build up of ___ in cells

convert sphingomyelin into ceramide sphinogomyelin

niemann pick disease presents with ___, ___ and ___

hepatosplenomegaly neurodegenerative course cherry red macula

metachromatic leukodystrophy follows ___ inheritance pattern

autosomal recessive

results from mutations in the enzyme arylsulfatase A

metachromatic leukodystrophy

removes a sulfate group from sulfatides

arylsulfatase A

metachromatic leukodystrophy results in accumulation of ___ in cells especially affecting ___ leading to the progressive destruction of these cells

sulfatides myelinated nervous cells

infantile form of metachromatic leukodystrophy presents with ____, ___, ___ and ___

loss of any speech acquired trouble walking loss of muscle tone paralysis

adult form of metachromatic leukodystrophy presents with ___, ___, ___

substance use problems difficulties in school psychiatric symptoms of delusions and hallucinations

metachromatic leukodystrophy results in nerves that stain ____

yellow brown with cresyl violet