Disorders of Metabolism

Question 1

Pyruvate dehydrogenase complex (PDH) deficiency

Answer 1

X-linked; buildup of pyruvate shunted to lactate and alanine;
neurologic defects, lactic acidosis, increased serum alanine starting in infancy

Question 2

Electron Transport Chain inhibitors (blocks ATP synthesis) & Uncoupling agents (produce heat)

Answer 2

Complex I: Rotenone
Complex III: Antimycin A
Complex IV: Cyanide, CO, Azide
ATP synthase (Complex V): Oligomycin
Uncoupling agents: 2,4-dinitrophenol, aspirin, thermogenin

Question 3

G6PD deficiency

Answer 3

decreased NADPH in RBCs; most common human enzyme def.

hemolytic anemia, Heinz bodies (denatured Hb), Bite cells

Question 4

Essential fructosuria

Answer 4

defect in fructokinase;

benign, fructose in blood and urine

Question 5

Fructose intolerance

Answer 5

deficiency in aldolase B;
Fructose-1-P accumulates which inhibits gycogenolysis and gluconeogenesis;
hypoglycemia, jaundice, cirrhosis, vomiting

Question 6

Galactokinase deficiency

Answer 6

deficiency in galactokinase, galactitol accumulates;

galactose in blood and urine, infantile cataracts, failure to track objects or develop social smile

Question 7

Classic galactosemia

Answer 7

absence of galactose-1-P uridyltransferase;
failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability, can lead to E. coli sepsis in neonates

Question 8

Lactase deficiency

Answer 8

stool has decreased pH and breath has increased Hydrogen w/ lactose tolerance test; normal mucosa in pts with hereditary lactose intolerance

Question 9

essential glucogenic amino acids

Answer 9

Met, Val, His

Question 10

essential glucogenic/ketogenic amino acids

Answer 10

Ile, Phe, Thr, Trp

Question 11

essential ketogenic amino acids

Answer 11

Leu, Lys

Question 12

acidic amino acids

Answer 12

neg charge;

Aspartate, Glutamate

Question 13

basic amino acids

Answer 13

Arg, Lys, His

Question 14

amino acids for growth

Answer 14

Arg, His

Question 15

amino acids in histones

Answer 15

Arg, Lys

Question 16

N-acetylgutamate deficiency

Answer 16

required cofactor for Carbamoyl phosphate synthetase I (Urea cycle);
leads to hyperammonemia;
in neonates: poorly regulated respiration and body temp, poor feeding, developmental delay, intellectual disability (identical presentation as in carbamoyl phosphate synthetase I def.)

Question 17

Ornithine transcarbamylase deficiency (OTC)

Answer 17

most common urea cycle disorder (only X-linked urea cycle disorder, others are AR);
excess carbamoyl phosphate converted to orotic acid;
increased orotic acid in blood and urine, decreased BUN, sx of hyperammonemia, NO megaloblastic anemia (vs. orotic aciduria);
infant is lethargic, poorly feeding, poorly controlled breathing and body temp

Question 18

PKU

Answer 18

disorder of aromatic amino acid metabolism leads to musty body odor;
screening occurs 2-3 days after birth (normal at birth b/c of maternal enzyme during fetal life)

Question 19

Maple syrup urine disease

Answer 19

decreased alpha-ketoacid dehydrogenase (B1) causes incrased alpha ketoacids in blood, blocks degradation of Isoleucine, Leucine, Valine;
CNS defects, intellectual disability, death

Question 20

Alkaptonuria (ochronosis)

Answer 20

deficiency of homogentisate oxidase in degradative pathway of tyrosine to fumarate leading accumulation of homogentisic acid in tissue;
dark connective tissue, brown pigmented sclerae, urine turns black on prolonged exposure to air, may have debilitating arthralgias

Question 21

Homocystinuria

Answer 21

d/t: 1) Cystathionine synthase def. 2) decreased affinity of cystathionine synthase for pyridoxal phosphate (B6) 3) Homocysteine methyltransferase (methionine synthase) def.;
increased homocysteine in urine, intellectual disability, osteoporosis, MARFANOID HABITUS, kyphosis, len subluxation (downward and inward), thrombosis, atherosclerosis

Question 22

Cystinuria

Answer 22

defect of renal PCT and intestinal amino acid transporter preventing reabsorption of Cysteine, Ornithine, Lysine, Arginine (COLA);
urinary cyanide-nitroprusside test is diagnostic

Question 23

Von Gierke disease (Type I)

Answer 23

Glucose-6-phosphatase def.

Question 24

Pompe disease (Type II)

Answer 24

Lysosomal alpha-1,4-glucosidase (acid maltase) def.

Question 25

Cori disease (Type III)

Answer 25

Debranching enzyme (alpha-1,6-glucosidase) def.

Question 26

McArdle disease (Type V)

Answer 26

skeletal muscle Glycogen phosphorylase (myophosphorylase) def.

Question 27

Andersen’s disease (Type IV)

Answer 27

Glycogen debranching enzyme def.

Question 28

Hers disease (Type VI)

Answer 28

hepatic Glycogen phosphorylase def.

Question 29

Fabry disease

Answer 29

alpha-galactosidase A def.;

Ceramide trihexoside accumulates

Question 30

Gaucher disease

Answer 30

Glucocerebrosidase def.;

glucocerebroside accumulates

Question 31

Niemann-Pick disease

Answer 31

sphingomyelinase def.;

sphingomyelin accumulates

Question 32

Tay Sachs disease

Answer 32

Hexosaminidase A def.;

GM2 ganglioside accumulates

Question 33

Krabbe disease

Answer 33

Galactocerebrosidase def.;

Galactocerebroside, psychosine accumulate

Question 34

Metachromatic leukodystrophy

Answer 34

Arylsulfatase A def.;

Cerebroside sulfate accumulates

Question 35

Hurler syndrome

Answer 35

alpha-L-iduronidase def.;

Heparan sulfate, dermatan sulfate accumulate

Question 36

Hunter syndrome

Answer 36

Iduronate sulfatase def.;

Heparan sulfate, dermatan sulfate accumulate

Question 37

Systemic Primary Carnitine deficiency

Answer 37

defect in tranport of LCFAs into mitochondria leads to toxic accumulation;
weakness, hypotonia, hypoketotic hypoglycemia

Question 38

Medium chain acyl-CoA dehydrogenase deficiency

Answer 38

decreased break down of FAs into acetyl-CoA leads to accumulation of 8-10 carbon fatty acyl carnitines in blood and hypoketotic hypoglycemia;
may present in infancy or early childhood w/ vomiting, lethargy, seizures, coma, liver dysfunction

Question 39

Hyperchylomicronemia (Type 1)

Answer 39

LPL def. or altered apolipoprotein C-II;

elevated Chylomicrons, TG, Cholesterol

Question 40

Familial Hypercholesterolemia (Type IIa)

Answer 40

absent or defective LDL receptors;

elevated LDL, cholesterol

Question 41

Hypertriglyceridemia (Type IV)

Answer 41

hepatic overproduction of VLDL;

elevated VLDL, TG

Question 42

Abetalipoproteinemia

Answer 42

decreased synthesis of apolipoprotein B leads to inability to generate chylomicrons, decreased cholesterol and VLDL secretion into blood thus fat accumulates in enterocytes