Enzyme Deficiency Disorders (Baker)

Question 1

What are the amino acid metabolism disorders?

Answer 1

Phenylketonuria (PKU), Oculocutaneous Albinism (OCA), Maple Syrup Urine Disease

Question 2

What are the carbohydrate metabolism disorders?

Answer 2

G6PDD, Galactosemia, Hereditary Fructose Intolerance

Question 3

Glycogen storage diseases affect what parts of the body?

Answer 3

Liver & muscles

Question 4

What are the glycogen storage disorders that affect the liver?

Answer 4

Von Gierke Disease, Cori Disease, Anderson Disease, Hepatic Phosphorylase Deficiency

Question 5

What are the glycogen storage diseases that affect muscle?

Answer 5

Pompe Disease & McArdle Disease

Question 6

What are the steroid metabolism disorders?

Answer 6

Congental Adrenal Hyperplasia (CAH) & Androgen Insensitivity Syndrome

Question 7

What is the lipid metabolism disorder?

Answer 7

Familial hypercholersterolemia

Question 8

What are the lysosomal storage disorders?

Answer 8

Mucopolysacchridoses, Sanfilipo Syndrome, Sphingolipodoses

Question 9

What are the nucleic acid metabolism disorders?

Answer 9

Adensosine Deaminase Deficiency & Lesche Nyhan Syndrome

Question 10

What are the porphyrin metabolism disorders?

Answer 10

Acute Intermittent Porphyria & Congenital Erythropoietic Porphyria

Question 11

Explain PKU.

Answer 11

Phenylalanine hydroxylase defienciency; can’t make tyrosine from phenylalanine. Seizures, intellectual impairments. Tx - dietary restrictions.

Question 12

Explain OCA.

Answer 12

Tyrosinase deficiency; can’t make melanin from tyrosine. No pigment in hair, eyes, skin, nystagmus.

Question 13

What are the 2 types of OCA?

Answer 13

Type 1: classical, chormosome 11q. Type 2: mutation on P gene of chromosome 15q.

Question 14

Explain Maple Syrup Urine Disease.

Answer 14

Branched-chain ketoacid-decarboxylase deficiency; can’t break down Val, Leu, or Ile - get build-up of amino acids. Urine smells like maple syrup, vomiting, death. Tx - dietary restrictions.

Question 15

Explain G6PDD.

Answer 15

G6P dehydrogenase deficiency - enzyme between 1st step (oxidative) of PPP pathway, which is particularly critical for RBCs. Low production of NADPH (reducer). Triggered by oxidative assault.

Question 16

Explain Galactosemia.

Answer 16

Galactose-1P uridyl transferase deficiency - enzyme that converts galactose-1P to G1P. Can’t break down dietary sugar. Vomiting, lethargy, failure to thrive, jaundice, mental retardation, cataracts, cirrhosis. Tx - dietary restrictions.

Question 17

Explain Hereditary Fructose Intolerance.

Answer 17

Fructose-1P aldolase deficiency - enzyme that converts fructose-1P to G3P. Can’t break down dietary fructose. Failure to thrive, vomiting, jaundice, seizures. Tx - dietary restrictions.

Question 18

Explain Von Gierke Disease.

Answer 18

Glucose 6-phosphotase deficiency - enzyme that converts G6P to glucose. No glycogen breakdown.

Question 19

Explain Cori Disease.

Answer 19

Amylo-1,6-glucosidase deficiency - enzyme that debranches glycogen to make G1P. No glycogen breakdown.

Question 20

Explain Anderson Disease.

Answer 20

Glycogen Brancher enzyme deficiency - enzyme that convertes UDP-G to glycogen. No glycogen synthesis.

Question 21

Explain Hepatic Phosphorylase Deficiency.

Answer 21

Glycogen phosphorylase deficiency - enzyme that converts glycogen to G1P. No glycogen breakdown.

Question 22

Which glycogen storage diseases result in no glycogen breakdown?

Answer 22

Von Gierke Disease, Cori Disease, Hepatic Phosphorylase Deficiency Syndrome, Pompe Disease, McArdle Disease

Question 23

Which glycogen storage disease results in no glycogen synthesis?

Answer 23

Anderson Disease

Question 24

Explain Pompe Disease.

Answer 24

Alpha-1,4-glucosidase lysosomal enzyme deficiency. No glycogen breakdown. Presents in infancy with hypotonia, enlarged heart, cardiac failure.

Question 25

Explain McArdle Disease

Answer 25

Muscle phosphorylase deficiency. No breakdown of glycogen during exercise. Presents in adolescence with muscle cramping during exercise.

Question 26

Explain CAH.

Answer 26

21-hydroxylase deficiency - enzyme that converts cholesterol to aldosterone/cortisol. Accumulation of adrenocorticosteroids leads to virilized female body. Tx - cortisol supplementation.

Question 27

Explain Adrogen Insensitivity Syndrome.

Answer 27

Defective testosterone receptors. 46 X,Y - externally female, internally male.

Question 28

Explain Familial Hypercholsterolemia

Answer 28

Problem with LDL receptor that leads to reduced/defective biosynthesis/transport and abnormal binding by/internalization of receptor. Increased endogenous synthesis of cholesterol. Very high cholesterol levels, xanthomata, early coronary events. Tx - dietary restrictions, statins.

Question 29

Explain Mucopolysaccharidoses. What syndrome is associated with this?

Answer 29

Can’t break down complex macromolecules - accumulation of sulfated polysacchrides (Hunter Syndrome). Skeletal, vascular, or CNS findings, coarsening of features.

Question 30

Explain Sanfilipo Syndrome.

Answer 30

Can’t break down complex macromolecules - accumulation of heparin sulfate. Skeletal, vascular, or CNS findings, coarsening of features.

Question 31

Explain Sphinogolipodoses. What syndromes are associated with this?

Answer 31

Can’t break down complex macromolecules - accumulation of lipids, glycolipids in brain, liver, spleen (Tay Sachs & Gaucher). CNS involvement, progressive mental deterioration, seizures.

Question 32

What is Tay Sachs?

Answer 32

Sphingolipodoses syndrome in which decrease in beta-hexoaminidase leads to increase in GM2 ganglioside. Poor feeding, lethargy, developmental delays, cherry red spot on fundus.

Question 33

What happens in Gaucher Types 1, 2, & 3?

Answer 33

Sphingolipodoses syndrome in which there is a decrease in glucosylceramide beta-glucosidase. Type 1 - pain in limbs, tendency to bone fracture, hepatomegaly, no CNS involvement. Type 2 - heavy CNS involvement, no treatment. Can treat types 1 &3 with analgesics or splenectomy.

Question 34

Explain Adenosine Deaminase Deficiency.

Answer 34

Adenosine deaminase deficiency - enzyme that converts adenosine/AMP to inosine/IMP. Immunodeficiency (“Bubble Boy”), problem with T/B cell signaling.

Question 35

Explain Lesche Nyhan Syndrome.

Answer 35

HGPRT deficiency - enzyme that converts hypoxanthine/guanine to IMP/GMP. Accumulation of purines leads to uric acid in blood. Uncontrolled movements, spasicity, mental retardation, compulsive self mutilation.

Question 36

Explain Acute Intermittent Porphyria.

Answer 36

Uroporphyrogin-I synthase deficiency - enzyme that converts porphobilinogen to hydroxymethyl-bilane. Increased secretion of poprphbilinogen and delta aminolevulinic acid in urine. Leads to vomiting, mental/emotional disturbance, coma.

Question 37

Explain Congenital Erythropoietic Porphyria.

Answer 37

Uroporphyrogen-3-cosynthase deficiency - enzyme that converts hydroxymethyl bilane to uroporphyrogen 3. Extreme photosensitivity, hemolytic anemia. Most require multiple transfusions and splenectomy.