Bio Chem enzymes step 1 contd

Question 1

This patient complains of fatigue exacerbated by exercise and associated muscle cramps suggesting exercise intolerance. These symptoms in combination with “tea-colored” (or in this case burgundy-colored) urine as well as elevated serum ammonia after exercise leads to a possible diagnosis of ?

Answer 1

McArdle disease (Type V glycogen storage disease).

McArdle disease involves the deficiency of the enzyme myophosphorylase, which converts glycogen to glucose-1-phosphate. Glucose-1-phosphate can then be converted to glucose-6-phosphate and enter glycolysis. The absence of muscle phosphorylase limits ATP generation by glycogenolysis resulting in an inability to fuel glycolysis during intense exercise and the characteristic symptoms identified in this patient’s presentation. Definitive diagnosis of this condition is by a muscle biopsy showing deficiency or absence of the enzyme myophosphorylase.

Question 2

Liver biopsy revealing deficiency of?

Answer 2

phosphorylase is seen in patients with type VI glycogen storage disease (Hers disease), which is characterized by hepatomegaly and growth retardation in childhood; however, the patient’s physical exam in this case is unremarkable

Question 3

Muscle biopsy showing a deficiency of ?

Answer 3

debranching enzyme would be observed in patients with type IIIa glycogen storage disease (Cori or Forbes disease). In this disease the individual is deficient in tissues solely outside skeletal myocytes, including the liver and heart, leading to early symptoms, including hepatomegaly, growth retardation, muscle weakness, hypoglycemia, hyperlipidemia, and elevated liver transaminase levels.

Question 4

Muscle biopsy revealing a deficiency of lysosomal a-glucosidase would be observed in patients with ?

Answer 4

type II glycogen storage disease (Pompe disease) and is the only glycogen metabolism disorder with a defect in lysosomal metabolism. Pompe disease is specifically associated with glycogen build-up in cardiomyocytes leading to hypertrophic cardiomyopathy.

Question 5

Muscle biopsy revealing deficiency of ?

Answer 5

phosphoglycerate kinase would present with muscle weakness, neurological symptoms, and hemolytic anemia. This patient does not show neurological symptoms or anemia.

Question 6

The BMP reveals a decrease in extracellular sodium (hyponatremia) and calcium (hypocalcemia) secondary to increases in intracellular concentration. Intracellular concentrations of sodium and calcium are increased with?

Answer 6

digoxin, a Na+-K+-ATPase inhibitor. In addition to its effects on the myocardium, it has similar effects on vascular smooth muscle via the same mechanism.

Question 7

Organophosphates are acetylcholinesterase inhibitors that lead to?

Botulinum toxin blocks the ?

Answer 7

an increase in acetylcholine concentration and associated muscarinic effects.

2. release of acetylcholine from presynaptic vesicles and interrupts neuromuscular function. It does not primarily affect calcium concentration

Question 8

Cocaine primarily increases?

Procainamide is a class I a sodium channel blocker. It would lead to ?

Answer 8

catecholamine concentration in the synaptic cleft and does not directly change intracellular ion concentrations.

2. decreased intracellular sodium concentration and increased extracellular sodium levels.

Question 9

Newborns who, within 48 hours of birth, show irritability, poor feeding, vomiting, lethargy, dystonia, and elevated levels of plasma leucine and alloisoleucine most likely?

Answer 9

have maple syrup urine disease (MSUD). Infants may also have a sweet “maple syrup” odor to their urine and cerumen, thought to be caused by a metabolite of isoleucine.

MSUD is caused by a deficiency of branched-chain a-ketoacid dehydrogenase complex (BCKDC), the second enzyme of the metabolic pathway that catabolizes the three branched-chain amino acids: leucine, isoleucine, and valine.

Question 10

Phenylketonuria is caused by ?

Answer 10

a deficiency of phenylalanine hydroxylase, resulting in intellectual disability and a “musty” body odor.

Question 11

Homocystinuria is caused by a deficiency in cystathione ß-synthase which catalyzes?

Answer 11

the conversion of homocysteine to cysteine. It is associated with Marfanoid habitus, developmental impairment, osteoporosis, ocular abnormalities, thromboembolic disease, and severe premature atherosclerosis.

Question 12

Cystinuria is a result of a deficiency in ?

Answer 12

a positively charged amino acid transporter in the proximal tubule, leading to cystine nephrolithiasis.

Question 13

Alkaptonuria is a deficiency in?

Answer 13

homogentisic acid oxidase, the third enzyme in tyrosine degradation. It manifests with a delayed darkening of urine and is otherwise asymptomatic in infancy.

Question 14

This preadolescent patient presents with signs and symptoms of pancytopenia, or aplastic anemia, which occurs when a person experiences a decrease in all three blood cell types: red blood cells, white blood cells, and platelets. His “dizzy spells” and the “funny feeling” in his chest are presyncope and palpitations caused by anemia (RBCs). His bleeding gums and nosebleeds are a symptom of thrombocytopenia (platelets), while his frequent infections suggest leukocytopenia (WBCs). In conjunction with pancytopenia, the patient’s abnormal skin (pigmented spots), skeletal (wide thumbs), and facial findings (small eyes) suggest ?

Answer 14

Fanconi anemia.

Question 15

Diamond-Blackfan anemia is a congenital erythroid aplasia that is characterized by?

Answer 15

progressive normochromic, macrocytic anemia with no other significant cytopenias.

Question 16

Edwards syndrome is a trisomy of chromosome 18 and is associated with?

Answer 16

a number of anomalies, including rocker-bottom feet, intellectual disability, clenched hands at birth, and heart defects.

Question 17

Hereditary spherocytosis (HS) is the most common hemolytic anemia due to?

Answer 17

a red cell membrane defect. Clinical presentation includes anemia, jaundice, and splenomegaly with a positive family history of hemolytic anemia.

Question 18

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome characterized by?

Answer 18

café-au-lait macules, axillary and/or inguinal freckling, Lisch nodules (iris hamartomas), osseous dysplasias, and neurofibromas.

Question 19

This patient’s “strange odor,” fair skin with eczematous rash, developmental delay, and immigration history has made the pediatrician concerned about ?

Answer 19

phenylketonuria (PKU). In the United States, this severe genetic disorder is usually discovered at birth upon routine newborn screening. Since it is an autosomal recessive disease, the patient’s parents must each be a carrier.

Question 20

PKU is most commonly caused by a deficiency of phenylalanine hydroxylase, the first enzyme in the breakdown pathway for phenylalanine. Phenylalanine hydroxylase converts phenylalanine to tyrosine, and then tyrosine hydroxylase converts tyrosine to DOPA. Both of these enzymes require a cofactor called?

Answer 20

tetrahydrobiopterin (BH4), which is regenerated by the enzyme dihydrobiopterin reductase.

An absence of dihydrobiopterin reductase yields even more devastating consequences. This disorder is known as malignant PKU. Important biological compounds that are affected by errors in this pathway include tyrosine, thyroxine, dopamine, melanin, norepinephrine, and epinephrine.

Question 21

Branched-chain α-ketoacid dehydrogenase deficiency is?

Answer 21

associated with maple syrup urine disease, manifesting with severe neurodegenerative effects, sweet-smelling odorous urine, and lethargy; cutaneous symptoms like the patient’s are not seen.

Question 22

Tyrosinase deficiency is associated?

Answer 22

with skin and eye albinism, but no urine odor or developmental delay as seen in this patient.

Question 23

Alkaptonuria, caused by?

Answer 23

deficient homogentisate oxidase, manifests with darkening of skin and urine that turns black on standing, but no developmental delay or eczematous skin rash.

Question 24

Dopamine β-hydroxylase is an enzyme involved in catechol synthesis. Deficiency manifests with?

Answer 24

severe hypotension and hypothermia, neither of which is seen in this patient.

Question 25

This patient presents with recent onset of muscle weakness and difficulty walking, which could be signs of developmental delay or regression. These findings are fairly general, but her histopathology report is suggestive of a specific etiology. Metachromasia refers to a property that enables a substance to shift the color spectrum such that the dye (eg, toluidine blue) will appear a different color (eg, reddish-pink) after application to the substance. Based on this key finding, the most likely explanation is that the patient has?

Answer 25

metachromatic leukodystrophy, an autosomal recessive disease caused by deficiency of the lysosomal enzyme arylsulfatase A

Question 26

Metachromatic leukodystrophy is an autosomal recessive lysosomal storage disease, most commonly due to ?

Answer 26

arylsulfatase A deficiency. It is distinguishable by the accumulation of sulfatides such as cerebroside sulfate, which have the ability to change the color of toluidine blue dye to reddish-pink (metachromasia).

Question 27

1. Tay-Sachs disease (β-hexosaminidase A deficiency) is notable for causing an ? 2. Krabbe disease (galactocerebrosidase deficiency) shows? 3. Fabry disease (α-galactosidase A deficiency) and Hunter syndrome (iduronate sulfatase deficiency) demonstrate?

Answer 27

“onion skin” appearance to the lysosomes. 2. multinucleated globoid cells on biopsy. 3. different clinical findings from this patient.

Question 28

Gaucher disease (glucocerebrosidase deficiency) or Niemann-Pick disease (sphingomyelinase deficiency) should reveal?

Answer 28

lipid-laden macrophages without metachromatic properties.

Question 29

This patient presents with lymphadenopathy and flaky plaques on the arms and legs. He also has recurrent bacterial and fungal infections and abscesses positive for Staphylococcus aureus. Together, the symptoms and history indicate that he has ?

Answer 29

chronic granulomatous disease (CGD), an immunodeficiency disease caused by a deficiency of nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase activity. Classically, patients have abscesses and are particularly susceptible to infections with S. aureus, Escherichia coli, and Aspergillus species. Other physical manifestations may include an eczema-like rash, lymphadenopathy, and hepatomegaly.

Question 30

CGD presents with recurrent infections, abscesses, hepatomegaly, lymphadenopathy, and scaly rashes. It is caused by a lack of NADPH oxidase, which uses ?

Answer 30

oxygen as a substrate.

Question 31

Carbon dioxide is a substrate for? 2. Tyrosine is an amino acid involved in ? 3. Interleukin-2 binds to ? 4 CD40 ligand allows for? 5. Superoxide is a substrate for ?

Answer 31

carbonic anhydrase. 2. a number of biochemical pathways, but not directly in immune function. 3. interleukin-2 receptors that are defective in patients with severe combined immunodeficiency. 4. T-cell activation by binding to CD40 on B cells. 5. superoxide dismutase, which converts the free radical into less reactive forms of hydrogen peroxide and water.