Usmle Step 1 Fa Biochemistry Metabolic Diseases

Front 1

MOA of arsenic

Back 1

Inhibits lipoic acid (required for pyruvate dehydrogenase complex). Results in vomiting, rice water stools, garlic breath.

Front 2

Cofactors required by pyruvate dehydrogenase complex
(also required for alpha ketoglutarate)

Back 2

1-pyrophopsphase (b1)
2-FAD (B2)
3-NAD (B3)
4-CoA (B5)
5-Lipoic acid

Front 3

Pyruvate dehydrogenase deficieincy
(a) cause
(b) findings
(c) treatment

Back 3

(1) congenital or acquired (B1 deficiency)-backup of alanine and pyruvate
(2) neurological defects
(3) incr intake of ketogenic nutrients (high fat or incr lysine and leucine-only purely ketogenic aa's)

Front 4

Fructose intolerance:
(a) deficient enzyme
(b) inheritence
(c) accumulated substrate
(d) Findings
(e) Treatment

Back 4

(a) aldolase B deficiency
(b) AR
(c) Fructose 1 phosphate accumulates (causes decr in phosphate and subs. Inhibition of glycogenolysis and gluconeogenesis)
(d) hypoglycemia, jaundice, cirrhosis, vomiting
(e) decr intake of fructose and sucrose (fruc+gluc)

Front 5

Essential fructosuria
(a) deficient enzyme
(b) inheritence
(c) Findings

Back 5

(a) Fructokinase defect
(b) AR
(c) Benign asymptomatic condition since fructose does not enter cells.
(d) Fructose appears in blood and urine.

Front 6

Classic galactosemia
(a) deficient enzyme
(b) inheritence
(c) accumulated substrate
(d) Findings
(e) Treatment

Back 6

(a) absence of galatose 1 phosphate uridyltransferase
(b) AR
(c) Damage caused by accum of toxic substances (like galactitol which acc in lens of eye)
(d) failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation
(e) exclude galactose and lactose (gal+gluc) from diet

Front 7

Galactokinase deficiency
(a) deficient enzyme
(b) inheritence
(c) accumulated substrate
(d) Findings
(e) Treatment

Back 7

(a) galactokinase
(b) AR
(c) galctitol accumulates
(d) mild condition; galactose in urine and blood, infantile cataracts. May initially present as failure to track objects or develop a social smile.
(e) exclude galactose and lactose from diet.

Front 8

Hyperammonemia
(a) Deficiency
(b) accumulated substrate
(c) Findings
(d) Treatment

Back 8

(a) May be acquired (liver dz) or hereditary (urea cycle defects)
(b) results in excess NH4+ which depletes alpha ketoglutarate leading to TCA inhibition
(c) ammonia intoxication: tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
(d) benzoate or phenylbutyrate to lower serum ammonia

Front 9

Ornithine transcarbamoylase deficiency
(a) deficient enzyme
(b) inheritence
(c) accumulated substrate
(d) Findings
(e) Treatment

Back 9

(a) Ornithine transcarbamoylase; interferes with ability to eliminate ammonia.
(b) X linked recessive (unlike other urea cycle defects which are RA)
(c) excess carbamoyl phosphate coverted to orotic acid
(d) orotic acid in blood and urine, decreased BUN, and symptoms of hyperammonemia.

Front 10

Phenylketonuria
(a) deficient enzyme
(b) inheritence
(c) Findings
(d) Treatment

Back 10

(a) decreased phenylalanine hydroxylase or tetrahydrobiopterin cofactor. Tyrosine becomes essential. Excess phenylalanine leads to phenylketones in urine.
(b) AR
(c) Mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor
(d) decreased phenylalanine and increased tyrosine

Front 11

Maternal PKU
(a) cause
(b) findings in infant

Back 11

(a) lack of proper dietary therapy during pregnancy
(b) microcephaly, mental retardation, growth retardation, congenital heart defects

Front 12

Alkaptonuria
(a) deficient enzyme
(b) inheritence
(c) Findings

Back 12

(a) homogentisic acid oxidase (degradative pathway of tyrosine)
(b) AR
(c) Benign disease. dark CT, pigmented sclera, urine turns black on standing. May have debilitating arthralgias.

Front 13

Albinism
(a) deficient enzyme
(b) inheritence
(c) Findings

Back 13

(a) Congenital deficiency of either tyrosinase (inability to synth melanin from tyrosine) or defective tyrosine transporters (decr amnts of tyrosine and thus melanin). Can result from lack of migration of neural crest cells.
(b)variable inheritence. Tyrosinase def is AR (NOTE: ocular albinism is KLR)
(c) Increased risk of skin cancer.

Front 14

Homocystinuria
(a) deficient enzyme (3 types)
(b) inheritence
(c) findings
(d) treatment

Back 14

((a)
1-cystathione synthase deficiency
2-decr affinity of cystathione synthase for pyridoxyl phosphate
3-homocysteine methyltransferase deficiency
(b) all AR
(c) Excess homocysteine and Cystine becomes essential. Increased homocysteine in urine. Mental retardation osteoporosis, tall stature, kyphosis, lens subluxation (down and in), and atherosclerosis (stroke and MI).
(d)
1-decr Met, incr Cyst, incr B12 and folate
2-incr vitB6 in diet

Front 15

Cystinuria
(a) enzyme defect(s)
(b) inheritence
(c) findings
(d) treatment

Back 15

(a) renal tubular aa transporters for cys, ornithine, ys, and aarg in PCT
(b) AR
(c) excess cystine can lead to precipitation of cystine kidney stones (staghorn calculi)
(d) acetazolamide to alkalinize the urine

Front 16

Maple syrup urine disease
(a) enzyme defect
(b) substrate increased
(c) symptoms

Back 16

(a) blocked degradation of branched aa (Ile, Leu, Val) due to decreased alpha ketoacid dehydrogenase.
(b) incr alpha ketoacids in blood, esp Leu
(c) severe CNS defects, mental retardation, and death.

Front 17

Adenosine deaminase deficiency

Back 17

Excess ATP and ADP imbalance nucleotide pool via feedback inhibition of ribonucleotide reductase which prevents DNA synth and decr lymphocyte count. One of the major causes of SCID

Front 18

Lesch-Nyhan syndrome
(a) deficient enzyme
(b) substrate increased
(c) inheritence
(d) Findings

Back 18

(a) HGPRT absence and subsequent defective purine salvage; normally converts hypoxanthine to IMP and guanine to GMP.
(b) excess uric acid production
(c) XLR
(d) retardation, self mutilation, aggression, hyperuricemia, gout, choreoathetosis

Front 19

Orotic aciduria
(a) enzyme deficiency
(b) inheritence
(c) findings
(d) treatment

Back 19

(a) Inability to convert orotic acid to UMP due to defect in orotic acid phosphoribosyltransferase or orotidine 5=phosphate decarboxylase.
(b) AR
(c) increased orotic acid in urine, megalblastic anemia (does not improve with B12 or folic acid), failure to thrive. No hyperammonemia.
(d) Oral uridine administration

Front 20

Von gierke's Disease
(a) Findings
(b) deficient enzyme

Back 20

(a) glycogen storage disease (type I) resulting in severe fasting hypoglycemia, highly incr glycogen in liver, increase blood lactate, hepatomegaly
(b) glucose 6 phsphatase

Front 21

Pompe's Disease
(a) Findings
(b) deficient enzyme
(c) comments

Back 21

(a) glycogen storage disease with cardiomegaly and systemic findings leading to early death
(b) lysosomal alpha 1,4 glucosidase (acid maltase)
(c) Pompe's trashes the Pump (heart, liver, muscle)

Front 22

Cori' disease
(a) Findings
(b) deficient enzyme
(c) comments

Back 22

(a) glycogen storage disease type III which leads to a milder form of type I (Von Gierke's) with normal blood lactate levels.
(b) debranching enzyme (alpha 1,6 glucosidase)
(c) gluconeogensis is intact.

Front 23

McArdle's disese
(a) Findings
(b) deficient enzyme
(c) comments

Back 23

(a) type V glycogen storage disease which increases glycogen in muscle but cannot break it down leading to painful muscle cramps, myoglobinuria w/strenuous exercise
(b) skeletal glycogen phosphorylase
(c) McArdle's=muscle

Front 24

Fabry's disease
(a) findings
(b) deficient enzyme
(c) accumulated substrate
(d) inheritence

Back 24

(a) peripheral neuropathy of hands/feet, angiokeratomas, CV/renal disease
(b) alpha galactosidase A
(c) cermaide trihexoside
(d) XR

Front 25

Gaucher's disease
(a) findings
(b) deficient enzyme
(c) accumulated substrate
(d) inheritence

Back 25

(a) hepatosplenomegaly, asceptic necrosis of femur, bone crisis, gaucher cells (macs that look like crumpled tissue). Most common
(b) beta glucocerebrosidase
(c) glucocerebroside
(d) AR

Front 26

Niemann Pick disease
(a) findings
(b) deficient enzyme
(c) accumulated substrate
(d) inheritence

Back 26

(a) progressive neurodegeneration, HSM, cherry red spot on macula, foam cells
(b) sphingomyelinase
(c) sphingomyelin
(d) AR

Front 27

TaySachs Disease
(a) findings
(b) deficient enzyme
(c) accumulated substrate
(d) inheritence

Back 27

(a) progressive neurodegeneration, developmental delay, cherry red spot on macula, lysosomes with onion skin
(b) hexosaminidase A
(c) GM2 ganglioside
(d) AR

Front 28

Krabbe's disease
(a) findings
(b) deficient enzyme
(c) accumulated substrate
(d) inheritence

Back 28

(a) peripheral neuropathy, developmental delay, optic atrophy, globoid cells
(b) galactocerebrosidase
(c) galactocerebroside
(d) AR

Front 29

Metachromatic leukodystrophy
(a) findings
(b) deficient enzyme
(c) accumulated substrate
(d) inheritence

Back 29

(a) central and peripheral demyilination w/ataxia and dementia
(b) arylsulfatase A
(c) cerebroside sulfate
(d) XR

Front 30

Hurler's syndrome
(a) findings
(b) deficient enzyme
(c) accumulated substrate
(d) inheritence

Back 30

(a) Developmental delay, gargoylism, airway obstruction, corneal clouding
(b) alpha L iduronidase
(c) heparan sulfate, dermatan sulfate
(d) AR

Front 31

Hunter's syndrome
(a) findings
(b) deficient enzyme
(c) accumulated substrate
(d) inheritence

Back 31

(a) Mild hurler's+aggressive behavior and no corneal clouding
(b) iduronate sulfatase
(c) heparan sulfate, dermatan sulfate
(d) XR

Front 32

Type I familial dyslipidemias hyperchylomicronemia
(a) increased
(b) elevated blood levels
(c) pathophysiology

Back 32

(a) chylomicrons
(b) TG, cholesterol
(c) lipoprotein lipase deficiency or altered apolipoprotein C-II

Front 33

Type II familial dyslipidemia (familial hypercholesterolemia)
(a) increased
(b) elevated blood levels
(c) pathophysiology

Back 33

(a) LDL
(b) cholesterol
(c) AD; absent or decr LDLR

Front 34

Type II familial dyslipidemia (hypertrigliceridemia)
(a) increased
(b) elevated blood levels
(c) pathophysiolgy

Back 34

(a) VLDL
(b) TG
(c) hepatic overproduction VLDL

Front 35

Abetaproteinemia
(a) defect
(b) inheritence
(c) findings

Back 35

(a) hereditary inability to synth lipoproteins due to deficiencies in apoB-100 and apoB-48.
(b) AR
(c) Sx appear in first few months of life; failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness