Biochem Questions Thread for Step 1

[MudPhud20XX]

Hi all, again I would like to begin posting biochem questions especially for MS2 who want to review while studying MS2 subjects. Just by doing a couple questions per day I think can make a big change. These are NOT from Uworld, First aid RX, and Kaplan.
Please feel free to add yours.

A 4-year-old boy is brought to the clinic because of a 2-week history of seizures that occur about every 3 days. Medical history is relevant for developmental delay with poor sitting and limited motor movements noticed at 12 months of age. He also has delayed language skills and swallowing difficulty that developed during the past 3 months. His vision and hearing have been deteriorating. Physical examination shows muscle weakness centrally and in all extremities. Fundoscopic examination shows a red spot on the retina. Which of the following is the most likely cause of this boy’s condition?

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[seminoma]

Hex A deficiency. Will post a question when I can think of one!

 

[MudPhud20XX]

Hex A deficiency. Will post a question when I can think of one!

yeah good job. it's tay-sach. so can anyone explain why not Niemman pick?

 

[aspiringmd1015]

vision is affected in tay sachs, not so sure about niemann picks

 

[usmleswot]

Niemman Pick would have hepatomegaly?

 

[MudPhud20XX]

exactly! so the below clinical vignette would be the Niemann pick.

A 3-month-old infant boy is brought to his pediatrician with rapidly progressive central nervous system deterioration and spasticity. Physical examination reveals marked hepatosplenomegaly. Liver biopsy shows an increase of sphingomyelin in the lysosomes.

 

[MudPhud20XX]

alright, so let's do some more of these. you guys pls free to fill in.

1. A 25-year-old Jewish man complains of a complains of weakness, nosebleed, and a feeling of fullness in the left side of his abdomen. He bruises easily and sustains fractures after minimal trauma. Physical examination shows massive hepatosplenomegaly. Bone marrow biopsy shows numerous macrophages with a “wrinkled paper” cytoplasm. The patient most likely has a deficiency of which enzyme?


2. A 16-year-old girl has clouding of the cornea, severe mental ******ation, hepatosplenomegaly, and vacuoles in the cytoplasm of peripheral blood leukocytes. To what are the findings most likely attributable?


3. A 35-year-old man presents with fatigue and fullness in the abdomen. Physical examination reveals hepatosplenomegaly. Laboratory studies show a normocytic anemia with neutropenia, thrombocytopenia, and pancytopenia. The photomicrograph shows a bone marrow aspirate. Which of the following lysosomal enzymes is most likely deficient?


4.A 24-year-old man who is mentally ******ed presents with spasticity in his limbs, emotional lability, and decreased visual-spatial discrimination. Urinalysis shows spherical granular masses in urinary sediment that stain positive with periodic acid–Schiff and Alcian blue. The patient most likely has a deficiency of which enzyme?


5. A 3-month-old infant boy is brought to his pediatrician with rapidly progressive central nervous system deterioration and spasticity. Physical examination reveals marked hepatosplenomegaly. Liver biopsy shows an increase of sphingomyelin in the lysosomes. Which of the following is the most likely diagnosis?

 

[MudPhud20XX]

vision is affected in tay sachs, not so sure about niemann picks

i am guessing the vision can also be affected in niemann pick to due to the “cherry-red”spot on macula. pls correct me if I'm wrong.

 

[seminoma]

i am guessing the vision can also be affected in niemann pick to due to the “cherry-red”spot on macula. pls correct me if I'm wrong.

Don't forget that the "cherry-red" spot is the normal macula. The area around it is depigmented.

 

[iki4life]

alright, so let's do some more of these. you guys pls free to fill in.

1. A 25-year-old Jewish man complains of a complains of weakness, nosebleed, and a feeling of fullness in the left side of his abdomen. He bruises easily and sustains fractures after minimal trauma. Physical examination shows massive hepatosplenomegaly. Bone marrow biopsy shows numerous macrophages with a “wrinkled paper” cytoplasm. The patient most likely has a deficiency of which enzyme?


2. A 16-year-old girl has clouding of the cornea, severe mental ******ation, hepatosplenomegaly, and vacuoles in the cytoplasm of peripheral blood leukocytes. To what are the findings most likely attributable?

3. A 35-year-old man presents with fatigue and fullness in the abdomen. Physical examination reveals hepatosplenomegaly. Laboratory studies show a normocytic anemia with neutropenia, thrombocytopenia, and pancytopenia. The photomicrograph shows a bone marrow aspirate. Which of the following lysosomal enzymes is most likely deficient?


4.A 24-year-old man who is mentally ******ed presents with spasticity in his limbs, emotional lability, and decreased visual-spatial discrimination. Urinalysis shows spherical granular masses in urinary sediment that stain positive with periodic acid–Schiff and Alcian blue. The patient most likely has a deficiency of which enzyme?


5. A 3-month-old infant boy is brought to his pediatrician with rapidly progressive central nervous system deterioration and spasticity. Physical examination reveals marked hepatosplenomegaly. Liver biopsy shows an increase of sphingomyelin in the lysosomes. Which of the following is the most likely diagnosis?

1.b-glucocerebrosidase
2.hurlers syndrome
3.b-glucocerebrosidase??
4.aryl-sulfatase A??
5. neimann pick disease

 

[MudPhud20XX]

1.b-glucocerebrosidase
2.hurlers syndrome
3.b-glucocerebrosidase??
4.aryl-sulfatase A??
5. neimann pick disease

you got it good job!

 

[MudPhud20XX]

Don't forget that the "cherry-red" spot is the normal macula. The area around it is depigmented.

good point, so I take that back...

 

[MudPhud20XX]

A 38-year-old man with chronic liver disease complains of involuntary flinging movements of his limbs. He states that other members of the family have had chronic liver disease, dementia, and abnormal body movements as well. Physical examination reveals an enlarged, firm liver and splenomegaly.

 

[SBR249]

Wilson's Disease, the basal ganglia is especially sensitive to copper accumulation. Damage in Wilson's Disease leads to hemiballismus.

 

[MudPhud20XX]

Wilson's Disease, the basal ganglia is especially sensitive to copper accumulation. Damage in Wilson's Disease leads to hemiballismus.

Good, Wilson it is... I also want to point out you get Low serum ceruloplasmin with Wilson

 

[MudPhud20XX]

An 18-year-old man sees his physician because of a rash and hair loss. He reports that in addition to consuming a balanced diet, he eats about 20 raw eggs per day to enhance his body-building exercises. What additional symptom is most likely in this patient?

 

[iki4life]

An 18-year-old man sees his physician because of a rash and hair loss. He reports that in addition to consuming a balanced diet, he eats about 20 raw eggs per day to enhance his body-building exercises. What additional symptom is most likely in this patient?

biotin deficiency

 

[MudPhud20XX]

very good, now if I were to put the answer choices what would you pick?

A. bleeding gums
B. dementia
C. glossitis
D. lactic acidosis
E. nystagmus

 

[Duke2018]

Glossitis

very good, now if I were to put the answer choices what would you pick?

A. bleeding gums
B. dementia
C. glossitis
D. lactic acidosis
E. nystagmus

 

[MudPhud20XX]

Glossitis

interesting that's what I chose but that's not the answer....

 

[Duke2018]

Is it dementia, then?

Glossitis fits more with the other B-vitamin deficiencies.

 

[MudPhud20XX]

so I thought this was a good question. what enzyme requires biotin?

 

[SBR249]

so I thought this was a good question. what enzyme requires biotin?

Pretty much any enzyme that does carboxylation.

 

[Duke2018]

Pyruvate carboxylase, acetyl-CoA carboxylase, amongst others

Are you thinking along the lines of poor fatty acid synthesis downstream of reduced acetyl-CoA carboxylase activity leading to limited myelination in neurons?

 

[MudPhud20XX]

Pyruvate carboxylase, acetyl-CoA carboxylase, amongst others

Are you thinking along the lines of poor fatty acid synthesis downstream of reduced acetyl-CoA carboxylase activity leading to limited myelination in neurons?

so the answer is lactic acidosis, since pyruvate carboxylase which needs biotin is not working pyrvuate is not being converted to OAA and being pushed to lactate. Does that makes sense?

 

[Sailey]

My.02 cents,
1. Gaucher is important because it is detectable and treatable and prevents reversible complications, examiners love these
2. Think of Wilsons as Ceruloplsmin disease not Copper disease, i.e, it is the deficiency of Ceruloplasmin that is responsible for this copper Sh.t.

 

[SBR249]

2. Think of Wilsons as Ceruloplsmin disease not Copper disease, i.e, it is the deficiency of Ceruloplasmin that is responsible for this copper Sh.t.

You will want to be careful with this. While it is fine to remember that ceruloplasmin is low in Wilson's disease, examiners will want you to know the pathophysiologic basis that leads to copper accumulation and it has nothing to do with ceruloplasmin. Wilson's disease arises as a result of defective copper secretion into the bile and this ties into a contrast with hemochromatosis because it tests whether you know the difference in how the body regulates iron and copper levels. Iron uptake is regulated at the point of entry from enterocytes into the blood stream so that the body will only absorb as much iron as it needs (because there's no established way of getting rid of excess iron aside from menstrual bleeding in women) whereas copper is freely absorbed but regulated at the point of secretion into bile. Hemochromatosis and Wilson's both hit points of regulation for their respective metals but the former's defect is in the enterocytes and the latter's defect is in the hepatocytes.

 

[MudPhud20XX]

You will want to be careful with this. While it is fine to remember that ceruloplasmin is low in Wilson's disease, examiners will want you to know the pathophysiologic basis that leads to copper accumulation and it has nothing to do with ceruloplasmin. Wilson's disease arises as a result of defective copper secretion into the bile and this ties into a contrast with hemochromatosis because it tests whether you know the difference in how the body regulates iron and copper levels. Iron uptake is regulated at the point of entry from enterocytes into the blood stream so that the body will only absorb as much iron as it needs (because there's no established way of getting rid of excess iron aside from menstrual bleeding in women) whereas copper is freely absorbed but regulated at the point of secretion into bile. Hemochromatosis and Wilson's both hit points of regulation for their respective metals but the former's defect is in the enterocytes and the latter's defect is in the hepatocytes.

is it just me? when you guys say "examiners love these," "examiners will want you to know" I get this auditory hallucinations (hopefully that doesn't last more than 6 months) from Dr. Sattar lol!

 

[MudPhud20XX]

A 7-year-old boy was brought to the clinic by his mother with the complaint that he is having episodes of acting and talking “as if he is drunk.” These episodes occur after stressful periods such as a febrile illness or fatigue. On examination, the boy has rapid breathing and rapid heart rate. Laboratory analysis shows elevated blood lactate and blood pyruvate, although the lactateyruvate ratio is normal. Blood pH is slightly acid at 7.30. Blood glucose and ketones are normal. No ragged red fibers are observed in a skeletal muscle biopsy. Which of the following is the most likely diagnosis?

 

[seminoma]

Good, Wilson it is... I also want to point out you get Low serum ceruloplasmin with Wilson

Yep and high 24hr urine urine copper (not urine ceruloplasmin). Saw this in a question, can't remember where though.

 

[Duke2018]

Probably not qualified to be attempting this but is it an Aldolase A mutation/deficiency? I know this can lead to hemolytic anemia post-febrile illness which would explain the elevated lactate and pyruvate, right? The elevated pH from lactic acid would then explain the increased respiratory rate.

A 7-year-old boy was brought to the clinic by his mother with the complaint that he is having episodes of acting and talking “as if he is drunk.” These episodes occur after stressful periods such as a febrile illness or fatigue. On examination, the boy has rapid breathing and rapid heart rate. Laboratory analysis shows elevated blood lactate and blood pyruvate, although the lactateyruvate ratio is normal. Blood pH is slightly acid at 7.30. Blood glucose and ketones are normal. No ragged red fibers are observed in a skeletal muscle biopsy. Which of the following is the most likely diagnosis?

 

[MudPhud20XX]

Probably not qualified to be attempting this but is it an Aldolase A mutation/deficiency? I know this can lead to hemolytic anemia post-febrile illness which would explain the elevated lactate and pyruvate, right? The elevated pH from lactic acid would then explain the increased respiratory rate.

actually it wasn't fair to give the question w/o answer choices.
here are the answer choices:
A. Hypoxia
B. mitochondrial dz
C. pyruvate carboxylase def
D. pyruvate dedhydrogenase def

 

[Sailey]

Answer is D
Both P carboxylase and P. dehydrogenase cause lactic acidosis.
Lactate to pyruvate ratio is high in P. carbo and low or normal with P.dehydrogenase
Other diseases, Mitochondrial(high), Glycogen storage diseases (low)
" a deficiency of E1 component of the Pyruvate Dehydrogenase complex is the most common biochemical cause of congenital lactic acidosis. This is X linked but because it is important in males and females, so classified X-linked Dominant. No treatment, but some respond to Thiamine"-------Lippincott.

SBR249 is right, Wilson is about copper excretion in bile. My bad.

 

[MudPhud20XX]

yup. D it is.

Option D (Pyruvate dehydrogenase deficiency) is correct. Pyruvate dehydrogenase deficiency results in the simultaneous appearance of lactate and pyruvate and the neurologic symptoms observed.

PYRUVATE DEHYDROGENASE COMPLEX DEFICIENCY
Most children with this enzyme deficiency present in infancy with delayed development and reduced muscle tone often associated with ataxia and seizures. Some infants have congenital malformations of the brain.
Comment. Without mitochondrial oxidation, pyruvate is reduced to lactate. The ATP yield from anaerobic glycolysis is less than a tenth of that produced from complete oxidation of glucose via the tricarboxylic acid cycle. The diagnosis is suggested by elevated lactate, but with a normal lactate/pyruvate ratio, i.e. no evidence of hypoxia. A ketogenic diet and severe restriction of protein (<15%) and carbohydrate (<5%) improves mental development. Such treatment ensures that the cells use acetyl-CoA from fat metabolism. A few children show a reduction in plasma lactate on treatment with large doses of thiamine, but the outlook is generally poor.

 

[MudPhud20XX]

A 4-year-old girl is rushed to the emergency department (ED) by her parents. She is confused and her speech is slurred. Her parents noted her to be hyperventilating and said her pulse was “racing”. She was found in the garage, and a bottle of antifreeze (ethylene glycol) was also seen on the ground with its lid off. The ED physician on duty considers giving intravenous ethanol to the girl. What would the physician’s rationale be for giving the girl ethanol?

 

[kagman]

A 4-year-old girl is rushed to the emergency department (ED) by her parents. She is confused and her speech is slurred. Her parents noted her to be hyperventilating and said her pulse was “racing”. She was found in the garage, and a bottle of antifreeze (ethylene glycol) was also seen on the ground with its lid off. The ED physician on duty considers giving intravenous ethanol to the girl. What would the physician’s rationale be for giving the girl ethanol?

I like the fact that the questions u post have no options.. But I hope NBME doesnt get a hang of your threads..lol..
Rational would be compete with Antifreeze at the ADH level.

 

[MudPhud20XX]

lol yeah.. thanks for the feedback. you got it. antifreezer.. it is. So here are the answer choices

A. to decrease formation of vanilyl mandelic acid
B. to decrease production of ceruloplasmin
C. to decrease production of oxalic acid
D. to increase formation of oxalic acid
E. to increase production of reitnal


The next question is:

A 60-year-old man with a history of cirrhosis of the liver owing to alcohol complains of chronic skin lesions. Physical examination shows blisters and pigmented scarring on his arms and other body parts that are exposed to sunlight. The patient’s urine sample has a light red-brown color. Urinalysis most likely would indicate an elevated level of

 

[Jabbed]

lol yeah.. thanks for the feedback. you got it. antifreezer.. it is. So here are the answer choices

A. to decrease formation of vanilyl mandelic acid
B. to decrease production of ceruloplasmin
C. to decrease production of oxalic acid
D. to increase formation of oxalic acid
E. to increase production of reitnal

C, which is a toxic metabolite of ethylene glycol metabolism. IRL though I'm pretty sure you just give fomepizole.

 

[Jabbed]

A 60-year-old man with a history of cirrhosis of the liver owing to alcohol complains of chronic skin lesions. Physical examination shows blisters and pigmented scarring on his arms and other body parts that are exposed to sunlight. The patient’s urine sample has a light red-brown color. Urinalysis most likely would indicate an elevated level of

Some type of porphyria, probably porphyria cutanea tarda. Betting on elevated uroporphyrin (not uroporphyrinogen!) in the urine.

 

[MudPhud20XX]

C, which is a toxic metabolite of ethylene glycol metabolism. IRL though I'm pretty sure you just give fomepizole.

you got it man. though I heard fomepizole is pretty expensive, so not sure in reality if ED will have those in stock.

 

[MudPhud20XX]

Some type of porphyria, probably porphyria cutanea tarda. Betting on elevated uroporphyrin (not uroporphyrinogen!) in the urine.

yup, it's the most common porphyria, porphyria cutanea tarda (photosensitivity differentiates from acute intermittent porphyria where you get incaresed porphobilinognes (instead of uroporphyrinogen)
(uroporphyrinogen) is correct. The patient’s findings of skin lesions in sun-exposed areas and a red-brown urine are characteristic of porphyria cutanea tarda. This is the most common type of porphyria and is seen most frequently in patients with alcohol-related liver disease. In healthy individuals, the I and III isomers of uroporphyrinogen are converted to coproporphyrinogen isomers by uroporphyrinogen decarboxylase. In patients with porphyria cutanea tarda, a deficiency of this enzyme causes uroporphyrinogen to accumulate in the skin (photosensitive) and be excreted in urine.

 

[Jabbed]

you got it man. though I heard fomepizole is pretty expensive, so not sure in reality if ED will have those in stock.

Just checked UpToDate, you're right. Mangement was 1. Bicarb 2. Fomepizole (preferred) or Ethanol 3. Hemodialysis

 

[MudPhud20XX]

A homeless 25-year-old man is found in an alley in a semicomatose state and is taken to the hospital. Other homeless people in the alley believe that he may not have eaten for several days. What is the most likely primary source of his blood glucose?

 

[Jabbed]

A homeless 25-year-old man is found in an alley in a semicomatose state and is taken to the hospital. Other homeless people in the alley believe that he may not have eaten for several days. What is the most likely primary source of his blood glucose?

Gluconeogenesis. Primary carbon source would depend on how long he's been starving. Assuming that it's been more than 3-4 days, I would say that glycerol (from lipolysis) is the primary source.

 

[Jabbed]

A 5-month-old infant had his first ear infection and was feeding poorly due to the ear pain. One morning the parents found the child unresponsive and rushed him to the ER. Blood glucose level was 45 mg/dL. The child became responsive after IV dextrose. Further blood analysis showed the absence of ketone bodies, normal levels of acyl-carnitine, and the presence of dicarboxylic acids. What is the likely enzymatic defect? What is the origin of the dicarboxylic acids?

 

[MudPhud20XX]

Gluconeogenesis. Primary carbon source would depend on how long he's been starving. Assuming that it's been more than 3-4 days, I would say that glycerol (from lipolysis) is the primary source.

good, gluconeogenesis it is.... thus, the muscle protein....
Option D (Muscle protein) is correct. The majority of amino acids used for gluconeogenesis come from muscle breakdown during extended fasting.

 

[MudPhud20XX]

A 5-month-old infant had his first ear infection and was feeding poorly due to the ear pain. One morning the parents found the child unresponsive and rushed him to the ER. Blood glucose level was 45 mg/dL. The child became responsive after IV dextrose. Further blood analysis showed the absence of ketone bodies, normal levels of acyl-carnitine, and the presence of dicarboxylic acids. What is the likely enzymatic defect? What is the origin of the dicarboxylic acids?

MCAD def???

 

[MudPhud20XX]

A 4-month-old infant girl is brought to the pediatrician for evaluation of decreased attention to her surroundings and a noticeable twitch. Her urine has a mousy odor, and laboratory studies show a positive Guthrie test. Which metabolic intermediate is most likely to be produced in lower amounts in this patient?

 

[MudPhud20XX]

You have received laboratory results of a patient’s plasma electrolyte concentrations. When the patient’s blood was drawn, the phlebotomist noted it had a soapy appearance and requested analysis of lipids and proteins. These levels were found to be elevated. You intend to recalculate electrolyte concentrations based on plasma water volume, rather than total plasma volume. Compared with a blood sample with normal plasma lipid and protein levels, what differences, if any, would be noted in anion and cation concentrations?

 

[MudPhud20XX]

A 6-year-old boy has pitting edema, abdominal pain, proteinuria, and hyperlipidemia. A kidney biopsy specimen indicates minimal change disease. The figure shows a normal electrophoretic pattern of albumin (Alb) and other plasma proteins. It also shows five abnormal patterns, each labeled with a capital letter. Which of the patterns is most likely to be seen in a patient with these symptoms?