Genetics Chapter 7: Disorders Of Metabolism

Front 1

what is the inheritance pattern of most inborn errors of metabolism

Back 1

autosomal recessive with a carrier state not associated with morbidity

Front 2

what is the most common monogenic disorder of carbohydrate metabolism

Back 2

transferase deficency galactosemia (1 in 30,000 newborns)

Front 3

what is the gene that is dysfunctional in most cases of galactosemia

Back 3

GAL-1-p-uridyl transferase

Front 4

what populations are more prone to galactosemia

Back 4

western europeans

Front 5

what are the clinical manifestations of classic galactosemia

Back 5

poor suck, failure to thrive, jaundice

untreated: sepsis, hyperammonemia, shock

cataracts (10%)

Front 6

accumulation of galactitol and galactonate in the blood may be a sign of which error of metabolism

Back 6

galactosemia

Front 7

what are long term effects of galactosemia

Back 7

poor growth, development, retardation

Front 8

what is the most common enzyme disorder that leads to defecits in fructose metabolism

Back 8

fructokinase deficency

Front 9

what are the clinical consequences of a fructokinase deficency

Back 9

asymptomatic fructosuria

Front 10

what are the consequences of a deficency in fructose 1,6 bisphosphatase

Back 10

impaired gluconeogenesis and acidemia

Front 11

what are the most common errors of carbohydrate metabolism

Back 11

glucose metabolism. usually heterogeneous causes (environmental and genetic)

ex. diabetes

Front 12

what is LPH and why do we need it

Back 12

LPH is lactase hydrolase which is encoded for on the lactase gene.

we need it to break down lactose which is found in breast milk.

lactose deficency can be due to nonpersistance or a more problematic congenital lactase deficency which is associated with malnutrition and severe dehydration in infants

Front 13

What 2 organs are most affected by glycogen storage disorders

Back 13

liver

skeletal muscle

Front 14

what are the 2 major causes of PKU

Back 14

#1 way more common is deficit in phenylalanine hydroxylase (PAH) this results in classic PKU

#2 is defect in dihydrobiopterin reductase which regenerates BH4 (tetrahydrobiopterin) and facilitates the PAH reaction

Front 15

what amino acid is the starting point for synthetic pathways of catecholamines

Back 15

tyrosine

Front 16

defecit in fumarylacetoacetate hydrolase results in what deficit

Back 16

tyrosinemia type 1

Front 17

excess fumarylacetoacetate in the blood may be indiciative of what disease

Back 17

hereditary tyrosinemia type 1

Front 18

a deficit in tyrosine aminotransferase may result in the following clinical symptoms? associated with which inborn error of metabolism?

Back 18

hereditary tyrosinemia type 2

corneal erosions, thickening of skin on palms, mental retardation

Front 19

what causes maple syrup urine disease

Back 19

error in metabolism of BCAAs

alpha ketoacid dehydrogenase (BCKAD) is required to break down BCAAs and if deficient causes maple syrup disease

maple syrup disease causes buildup of ketoacids and stunts growth and development if untreated can be fatal

Front 20

what is the most common inborn error of fatty acid metabolism

Back 20

deficiency of medium chain acyl coenzyme A dehydrogenase (MCAD)

Front 21

when does a MCAD deficiency often manifest

Back 21

in fasting states (when fatty acids would usually be oxidized to ketones)

Front 22

what are the symptoms of untreated MCAD deficiency

Back 22

vomiting and fatty acid accumulation, culmination is exhaustation of glucose suppy with cerebral edea and encephalopathy

Front 23

What is LCHAD deficiency?

Back 23

long chain hydroxyacyl coa dehydrogenase deficiency. FAO disorder with a worse prognosis than the more common MCAD deficiency

Front 24

The final step of cholesterol synthesis is catalyzed by what enzyme? Failure of this enzyme results in what condition?

Back 24

(Triangle)7-sterol reductase (DHCR7)

Smith-lemli-opitz syndrome

Front 25

what is unusual about SLO?

Back 25

it produces various congenital malformations. Most inborn errors of metabolism do not cause congenital malformations

Front 26

what condition results from a CYP21A2 mutation?

Back 26

CAH, loss of gluco/mineralcorticoid production, increased adrenal androgen secretion

Front 27

what will female infant with CAH have?

Back 27

ambiguous genetalia , can have salt wasting

Front 28

what will boys with CAH have?

Back 28

salt wasting

Front 29

what is salt wasting

Back 29

decreased aldosterone leads to increased loss of Na/Cl/H2O and retention of K+

Front 30

what is CAIS/PAIS? how does it affect 46,XY persons?

Back 30

complete or partial androgen insensitivity.

in males it will ambiguous or female appearing external genetalia and failure to produce male secondary sex characteristics

Front 31

What is the most severe Peroxisomal Biogenesis Deficiency (PBD)? What are its symptoms?

Back 31

zellweger dsisease.

severe hypotonia, progressive disease of white matter, and usually death in pregnancy

Front 32

zellweger syndrome

adrenoleukodystrophy

refsum

and rhizomelic chondroysplasia type 1 are all what type of disorder

Back 32

Peroxisome biogenesis disorders

Front 33

what is the most common PED (single peroxisomal enzyme deficiency)

Back 33

X linked adrenokeukodystrophy (ALD)

Front 34

what are MPS disorders

Back 34

MPS disorders (mucopolysaccharidoses) are caused by a reduced ability to degrade one or more glycosaminoglycans

They are characterized by progressive multisystem deterioration

Front 35

What are Type I, II MPS diseases

Back 35

iduronidase (type 1) prototical MPS disorder

hunter syndrome (type 2) associated with iduronate sulfatase

Front 36

What are the 3 types of Gaucher disease

Back 36

deficiency of lysosomal enzyme: glucosylceramidase (glucocerebrocyde) results in accumulation of glucosylceramide

type 1- no CNS

type 2- yes CNS

type 3- mix of 1 and 2

Front 37

What is the N370S allele

Back 37

mutant GBA allele that is associated with a milder (Type 1) gaucher's disease

Front 38

what are 2 major functions of the urea cycle

Back 38

removal of nitrogenous wastes as urea

de novo arginine synthesis

Front 39

how are urea cycle disorders inherited (hint OTC)

Back 39

autosomal recessive

OTC is X linked recessive, also most prevalent

Front 40

What is a deficency in the PDH complex result in?

Back 40

lactic acidemia and developmental delay

Front 41

what causes cystineuria

Back 41

abnormal transport between cells and extra cellular environment

result is buildup of cystine, lysine, arginine, and ornithine

Front 42

what is cystinosis

Back 42

diminished ability to transport cystine across the lysosomal membrane. accumulation of cystine crystals develobs in most tissues

Front 43

what is the most insoluable amino acid? what does accumulation of this amino acid cause

Back 43

cystine

nephrolithiosis and infectio

Front 44

What is Menkes disease (MND)?

Back 44

X linked recessive disorder of copper metabolism that results in inability to transport copper fro intestinal cells to blood resulting in a deficiency of copper. Symptoms include mental retardation, siezures, loose skin, death

Front 45

What is Wilson Disease (WND)?

Back 45

Copper excess caused by defective excretion of copper into the biliary tract

it results in hepatolenticular degeneration, arthropathy, cardiomyopathy, kidney damage

Front 46

what is the kayser-fleisher ring? when do you see it?

Back 46

deposition of copper in the eye that you see in 95% of wilson syndrome patients

Front 47

what is acrodermatitis enteropathica (AE)

Back 47

caused by a deficit in absorption of zinc in the GI tract that results in growth retardation and immune disfunction

a hallmark sign is dermatitis

Front 48

what is hereditary hemochromatosis

Back 48

inherited disorder where excess iron is absorbed and stored in various organs

manifests with joint pain diminished libido diabedes and increased pigmentation of skin