Lysosomal storage diseases form a category of genetic disorders result

Question

Lysosomal storage diseases form a category of genetic disorders resulting from defective enzymes that normally function to degrade unneeded molecules in cells. These enzymes do their work in the lysosome, a small compartment in a cell analogous to a garbage disposal. The lysosome contains between thirty and forty different degradative enzymes. When any one of the lysosomal enzymes is defective, the molecules requiring that specific enzyme for their degradation will accumulate and cause that individual's lysosomes to swell enormously. The physiological effects of such swelling on the individual include motor and mental deterioration, often to the point of premature death. But each disease resulting from one specific defective lysosomal enzyme has its own characteristic pathology. The age of onset, rate of progression, and severity of the clinical symptoms observed in patients with the same defective lysosomal enzyme are highly variable. For many years, this variability in patients with the same defective enzyme puzzled scientists. Only recently have researchers begun to answer the riddle, thanks to a genetic analysis of a lysosomal storage disorder known as Tay-Sachs disease.

As in most lysosomal storage diseases, patients suffering from Tay-Sachs disease show both mental and motor deterioration and variability in age of onset, progression, and severity. Physicians have categorized the patients into three groups: infantile, juvenile, and adult, based on onset of the disease. The infantile group begins to show neurodegeneration as early as six months of age. The disease advances rapidly and children rarely live beyond 3 years old. The first symptoms of the disease appear in juvenile cases between 2 and 5 years of age, with death usually occurring around age 15. Those with the adult form generally live out a normal lifespan, suffering from milder symptoms than do those with the infantile and juvenile forms. Researchers hoped that the categorization would yield insight into the cause of the variability of symptoms among Tay-Sachs patients, but this turned out not to be the case.

In Tay-Sachs disease, undegraded materials accumulate mainly in the lysosomes in the brains of patients, but the kinds of molecules left undegraded and the specific identity of the defective lysosomal enzyme responsible for the malfunction were not discovered until the 1950s and 60s, respectively. The main storage molecule was found to be a lipid-like material known as GM2 ganglioside. The defective enzyme was later identified as hexosaminidase. In 1985, the gene coding for the normal hexosaminidase enzyme was cloned and its DNA sequence determined. Shortly thereafter, the DNA sequences of genes encoding hexosaminidase from many Tay-Sachs patients were studied. It soon became apparent that not one or two but many different types of mutations in the hexosaminidase gene could result in Tay-Sachs disease. Some of the mutations prevented the synthesis of any hexosaminidase, preventing all such enzyme activity in the cell. Patients with this type of mutation all had the infantile form of Tay-Sachs disease. Other mutations were found in certain regions of the gene coding for areas of the enzyme known to be critical for its catalytic activity. Such mutations would allow for only extremely crippled hexosaminidase activity. Most of the patients with these mutations clustered in the juvenile category. Adult Tay-Sachs patients presented mutations in the regions of the hexosaminidase gene that were less important for the enzyme's activity than were those affected in juvenile patients. Scientists quickly hypothesized that the variation in age of onset and severity of Tay-Sachs disease correlated with the amount of residual enzymatic activity allowed by the genetic mutation. Though more research is needed to demonstrate similarity with other lysosomal storage diseases, the work done on Tay-Sachs disease has already offered a promising glimpse into the underlying mechanisms of these disorders.   1 
 D 
 Q1. The passage suggests that which of the following lines of inquiry would be most useful in determining the relevance of the research done on Tay-Sachs disease to lysosomal storage diseases generally?

(A) Do patients suffering from other lysosomal storage diseases have the same mortality rate as those suffering from Tay-Sachs? 
(B) Do other lysosomal storage diseases affect the hexosaminidase gene? 
(C) How many different mutations are present in the defective genes responsible for other lysosomal storage diseases? 
(D) Does the onset of other lysosomal storage diseases vary with the location of mutations in DNA sequences? 
(E) What purpose does GM2 ganglioside serve in the human body?

2 
 C 
 Q2. It can be inferred from the passage that which of the following statements is true of lysosomal storage diseases?

(A) They are generally caused by mutations to the hexosaminidase gene. 
(B) They are undetectable until physical symptoms are present. 
(C) They can be fatal even when allowing some enzymatic activity. 
(D) They are most lethal when onset is in a patient's infancy. 
(E) Their causes were unknown before the 1950s.

3 
 B 
 Q3. The author of the passage is primarily concerned with

(A) illuminating the physiological consequences of Tay-Sachs disease 
(B) explaining the importance of research on a specific disease to other diseases of that type 
(C) arguing for a more detailed examination of lysosomal storage diseases 
(D) challenging a traditional view of a class of diseases as incomplete 
(E) describing the implications of genetic mutations for mortality rates

Manhattan CAT 3

parker · Accepted Answer

Really tough passage. RC is one of my strengths, and it still took me 7 min to do this passage and the associated questions.

If you're like me, you probably have an "oh crap" meter that kicks in pretty quickly after starting a passage. If you're not a science person, that meter probably kicked in *really* quickly here. When/if that happens, you have two options (1) panic or (2) focus even more. And although it may not seem to be the case, the path you take *is* a choice. What are the concrete things that you DO understand? What are the  structural  elements of the passage that will allow you to map out what is important and what is microscopic detail you may not need to pay attention to?

My mental process reading and taking notes on this passage went something like what is below. My thoughts are in parentheses, and the structural words I paid attention to are highlighted. In general, when I read--ESPECIALLY if it's a topic I don't understand--my mental highlighter pops out for  structure words .

Lysosomal storage diseases  (looks like it's going to be a science psg)   form a category  of genetic disorders  resulting  from defective enzymes that  normally  function to break down unneeded molecules in cells.  (part of a category...ok)  These enzymes do their work in the lysosome, a small compartment in a cell  analogous  to a garbage disposal.  (lysowhatever =cellular garbage disposal)  When  any   one  of the lysosomal enzymes is defective, the molecules that  would have  been broken down by that enzyme  instead  accumulate and  cause  that individual's lysosomes to swell enormously,  resulting  in motor and mental deterioration,  often  to the point of premature death.  (broken garbage disposal...overflow...bad outcome)  The age of onset, rate of progression, and severity of the clinical symptoms observed in patients with the  same  defective lysosomal enzyme are  highly variable .  For many years,  this variability in patients with the  same  defective enzyme puzzled scientists.  Only recently  have researchers  begun  to answer the riddle, thanks to a genetic analysis of a  particular  lysosomal storage disorder known as Tay-Sachs disease.  (BINGO-- contender for main thought...looks like this is going to be a problem-solution type passage)

NOTES FOR PARAGRAPH 1:
LSD-genetic disorder (defective enzymes in lyso. --cell garbage disp.)
broken disp->swelling/death?
symptoms VAR.
 RECENTLY begun to answer WHY VAR. thanks to TSD (type of LSD)

As in  most  lysosomal storage diseases, patients suffering from Tay-Sachs disease show  both  mental and motor deterioration and variability in age of onset, progression, and severity.  (ok still focus on VAR...paragraph will be about this)   Physicians have  categorized  the patients into  three  groups based on onset of the disease: infantile, juvenile, and adult.  (3 types, ok)  The infantile group  begins  to show neurodegeneration as early as six months of age and children  rarely  live beyond 3 years old. The  first  symptoms of the disease appear in juvenile cases between 2 and 5 years of age, with death  usually  occurring around age 15. Those with the adult form  generally  live out a normal lifespan, suffering from milder symptoms than those with the infantile and juvenile forms.

NOTES FOR PARAGRAPH 2:
 VAR in onset, progress, severity 
Inf-show @ 6 mo, die @ 3 yr
Juv-show@ 2-5, die @ 15
Adult-normal die, mild

In Tay-Sachs disease, scientists were aware that molecules accumulated mainly in the brains of patients, but they did not discover the specific identity of the defective lysosomal enzyme responsible for the malfunction, hexosaminidase, (culprit=hexoblahblah)   until the 1960s.  (id specific enzyme....first specific date in psg! chronology starting...a lot of science-y words focus on DATES and subject-verbs to get gists of sentences)  In  1985 , the DNA sequence for the normal enzyme was determined.  Shortly thereafter , the DNA sequences of genes encoding hexosaminidase from  many  Tay-Sachs patients were studied. It  soon  became apparent that  not   one or two   but many  different types of mutations in the hexosaminidase gene  could result  in Tay-Sachs disease.  (many diff causes)  These different mutations  resulted  in  various  levels of impaired enzymatic activity; those in the infantile category had  little to no  normal activity, while those in the adult category suffered  only moderate  impairment.  (infant/adult diff...)  Scientists quickly hypothesized that the variation in age of onset and severity of Tay-Sachs disease  correlated with  the amount of residual enzymatic activity allowed by the particular genetic mutation a patient had.  Though more  research is needed to demonstrate similarity with  other  lysosomal storage diseases, the work done on Tay-Sachs disease has  already  offered a promising glimpse into the underlying mechanisms of these disorders. 
 
NOTES FOR PARAGRAPH 3:
ID enz. (hex.) in '60s
'85 seq. normal enz., LATER-> TS hex. seq.
MANY mutations -> diff in inf/adult TS
 sci: VAR effects bc of var mutations ....promising glimpse of LSD mech !

Took me a little longer than I would have liked (close to 4 min) but I can forgive myself bc (1) it was a really tough passage (2) I tend to skew more twds quickly moving through questions after taking slightly longer to read and (3) not forgiving myself wouldn't do me any good---I just spent 4 min so what I need to spend my time on is focusing on the next task, *not* beating myself up for spending 1 more min than the "ideal" test taker.

Q.1
Q is about relevance of TSD research to general LSD...
Thought process...was this vaguely alluded to in P1? Quick look at my notes says no--oh wait, it's that last underlined part in my P3 notes.
(A) mortality rate? not relevant--research was about mutation (mortality rate was in P2, and more about categorization than research)  Out. 
(B) hexoblahblah gene was specifid TSD culprit, but promise was about underlying MECHANISM of "VAR mutations-> VAR effects" not the enzyme itself.  Out .
(C) Hmmm...something related to number of diff mutations...I don't exactly understand what this says on a first quick read so I'll  leave it for now and keep going. 
(D) Pretty much what the last sentences said about TSD...var mutation->var effects.  Keep it. 
(E) Purpose of hexoblahblah...don't care (for same reason as choice B).  Out.

I'm down to C and D, and D looked pretty good. I take one more (careful) read of C to be sure. Would the answer to the question in choice C, a *number*, provide useful information about how the mechanisms are analogous? Beyond knowing that the number is greater than 1, probably not. Whereas with D, knowing the link between different ages of onset/severities and different mutations is exactly the kind of mechanism explored with TSD.  Vote for D.

Q.2
(A) Sneaky GMAC, I see your trap-- no, hexoblahblah was the culprit for TSD, not LSD in general.  Out. 
(B) Can't remember from passage,  leave it for now. 
(C) Can't remember from passage,  leave it for now. 
(D) Same trap as A.  Out. 
(E) Dates only mentioned in reference to ID-ing enzymes for TSD.  Out.

Now I search through the passage to choose between B and C. LSD in general are talked about a lot in P1. The third sentence of P1 says when  ANY ONE  of the enzymes is defective, bad things happen (up to and including death).
 I'll go with C.  (B makes a strong black-and-white claim--"undetectable" that I can't find concrete evidence for, and since C lines up with what the passage says there isn't a reason for me to waste more time looking.)

Q.3
A general question--phew. I've done a lot of hard work already so this one should come quickly. The passage mainly seemed to focus on recent research findings for TSD (var mutations=var manifestations of disease) and how this could illuminate the larger category of LSDs.

(A) Does not mention link between TSD and LSDs.  Out. 
(B) Pretty much what I said above.  Keep it. 
(C) Arguing against who? It seems like scientists are looking into this stuff in detail already.  Out. 
(D) What is the "traditional view"?  Out. 
(E) The first part of this sounds good, but the second ("mortality rates") is too narrow-- there are all kinds of implications (age of onset, severity, etc).  Out.

Wow, this is a LONG post. RC is really hard to cover in detail without, well, a lot of details. And RC approaches/note-taking will vary tremendously among students. But as you're working on a really challenging passage, the most important thing is to pay attention to the  specifics in structure (NOT of content details...that part comes later, when you're answering questions)  --don't let passage itself overwhelm you by becoming a general wash of verbiage. And if you didn't understand the passage entirely (and I'm not even sure I did...there's a lot of technical stuff in there that I didn't both trying to grasp fully), there are still some answer choices that you can eliminate based on what you specifically DID understand. After you've eliminated what you can eliminate, just guess and move on, no hard feelings. Hope this helps.

parker · Answer

Oh my goodness, I'm so sorry I just saw that I hadn't replied to this! You may have already taken your test but just in case--

Your Questions:
1. Yes, I absolutely write notes. There's way too much information to hold in my brain, so I make a structural map of the passage as I go along-- we teach something called the "skeletal sketch" in classes; this method focuses on comprehending much of the first paragraph and only the gist of the second. Within that technique there is a still a spectrum of how much/little people write for their own comfort levels--I tend to read pretty quickly but need to stay active to not have my attention wander, so I may write a little more than others. The important thing is to avoid getting bogged down in details during the entire passage-- comprehending every single thing is not your goal (it would take waaay to long and probably not yield you many points. The heavy detail work is for (1) when you're reading the beginning of the passage to get the gist and (2) when you go back to the passage while answering specific questions).

2. The answer to your second question is related to the answer to your first-- do NOT try to comprehend everything-- there's not enough time, so don't stress out if you don't grasp every little detail. Structure and main point are your goals for the first read. The little details can be dealt with if (and only if!) you're asked about them in the questions--you get points for correct answers, not for total comprehension

satts · Answer

The answer to question 2 is C

There is no information regarding the number of death proportional to onset. It does say infantile death does occur, but the information would be false if it were known that no of cases of infantile diseases is very very less as compared to adolescent

lets say perhaps out of 1000 2 infantile cases but 50 adolescent cases

without concrete info D cannot be true.

sikalvag · Answer

answer for the second question is 'C' i got it from other forums
Explanation is (C) CORRECT. This choice states that it can be inferred that lysosomal storage diseases "can be fatal even when allowing some enzymatic activity." This can be inferred from the fact that people suffering from juvenile Tay-Sachs have "extremely crippled hexosaminidase activity" (lines 91-93) and generally live to only 15 years of age (line 49).

rlevochkin · Answer

D-found in the last 3 sentences of the paragraph. The puzzling question is what causes variability. Scientists are less concerned to figure out the number of possible genetic mutations of the deseases (even though it might be the next step of the research) , they would be happy enough to figure out the cause of variability before they go any futher.

D

B

D

B

eybrj2 · Answer

OA is DCB.

I have a question regarding Q2.

This is explanation provided by Manhattan, but I don't agree with it, especially red parts.

(A) This choice states that it can be inferred that lysosomal storage diseases "are generally caused by mutations to the hexosaminidase gene ." The passage only states that mutations in this gene are responsible for Tay-Sachs disease.  There is no information suggesting that it is responsible for the entire class of storage diseases.

(B) This choice states that it can be inferred that lysosomal storage diseases "are undetectable until physical symptoms are present." The passage, however, discusses some specific genetic mutations that are linked to Tay Sachs diseases, a type of lysosomal storage disease. This indicates, if anything, that the disease might be detectable before physical symptoms are present.

(C)  CORRECT.  This choice states that it can be inferred that lysosomal storage diseases  "can be fatal even when allowing some enzymatic activity."  This can be inferred from combining two statements in the passage: paragraph 3, which states that “those in the infantile category had little to no normal activity” and paragraph 2, which states that  “children   rarely live beyond 3 years old.”  "Little... activity," while low, is still not zero activity.
 
(D) This choice states that it can be inferred that lysosomal storage diseases "are most lethal when onset is in a patient's infancy."  The information in the passage relating to infant mortality is given in the specific context of Tay-Sachs disease.  We cannot know whether this pattern holds true for other diseases of this type. In addition, while those with the infantile form do die of the disease, so do those with the juvenile form, making the disease equally lethal.
 
(E) Choice E states that it can be inferred that the causes of lysosomal storage diseases were unknown before the 1950s. The passage states, however, that the causes of Tay-Sachs disease were unknown before that time. We do not have any information about the causes of lysosomal storage diseases generally.

The explanation says that the reason that A and D are not the answer is that A and D can be applied only to Tay-Sachs disease.
But dosen't the explanation for C also talk about Tay-Sachs disease ? “those in the infantile category had little to no normal activity” 
 children   rarely live beyond 3 years old.”

jagdeepsingh1983 · Answer

My Answers were DBB for above package, but for 2nd question after reading explanation,

I think C is the correct answer as per explanation provided "little to no normal activity".. I find this logical statement means there is some activity is allowed children do not live beyond 3 years. if we ignore this inference then statement made in above paragraph fails.

I agree with Manhattan explanation

zerosleep · Answer

My answers are- 1) C 2) D 3) B
It took me nearly 9- 10 mins to solve this question, certainly more than double the time ideal time. This passage is 600 words. Can we expect such long passages with only 3 question on the GMAT. If yes, I probably need to improve my timings.. :D

I have one more doubt- how to effectively tackle and let go of few sentences that I could not understand properly. Why I spend extra time in sentences I dont understand is beacuse I have mostly seen questions coming from that specific part of the passage. (I am sorry I cant provide any example in this passage though)..

alman888 · Answer

I answered with DCB in 8 minutes.

I freaked out halfway through the first paragraph and spent more than one minute on it to: (1) understand what was written because my eyes were glazing over(!), and (2) calm myself down. The second paragraph was more descriptive and easier to read, and the third was technical and somewhat over my head.

Used process of elimination on questions 1 and 2 (basically looking in the passage for the key words in the answer choices - tedious, perhaps, but I'm never going to remember details), and could solve 3 pretty quickly.

Let's hope I can reproduce this performance on test day!

bolasao · Answer

Hi,

About question 2. The explanation to the question states that A, B, D and E are out because it refers to "Tay-Sachs disease" and not to "lysosomal storage diseases" in general.

The thing is that to infer answer C you also need information about the "Tay-Sachs disease". As the answer asserts " C can be inferred from combining two statements in the passage: paragraph 3, which states that “those in the infantile category had little to no normal activity” and paragraph 2, which states that “children   rarely live beyond 3 years old.” "Little... activity," while low, is still not zero activity. " Hence, I am completely lost because, in fact, no of the answer referse specifically to "lysosomal storage diseases".

Please help, thank you

Silviax · Answer

I had this passage on my practice exam today and answered all questions correctly except for # 2.

I honestly still don't understand why the right answer is C.

These are the official answer explanations from Manhattan:
I highlighted what confuses me. Read my comments below the passage.

A) This choice states that it can be inferred that lysosomal storage diseases "are generally caused by mutations to the hexosaminidase gene."  The passage only states that mutations in this gene are responsible for Tay-Sachs disease. There is no information suggesting that it is responsible for the entire class of storage diseases. 
 
 (B) This choice states that it can be inferred that lysosomal storage diseases "are undetectable until physical symptoms are present." The passage, however, discusses some specific genetic mutations that are linked to Tay Sachs diseases, a type of lysosomal storage disease.   This indicates, if anything, that the disease might be detectable before physical symptoms are present.
 
(C) CORRECT. This choice states that it can be inferred that lysosomal storage diseases "can be fatal even when allowing some enzymatic activity."  This can be inferred from combining two statements in the passage: paragraph 3, which states that “those in the infantile category had little to no normal activity” and paragraph 2, which states that “children   rarely live beyond 3 years old.” "Little... activity," while low, is still not zero activity. 
 
(D) This choice states that it can be inferred that lysosomal storage diseases "are most lethal when onset is in a patient's infancy."  The information in the passage relating to infant mortality is given in the specific context of Tay-Sachs disease.  We cannot know whether this pattern holds true for other diseases of this type. In addition, while those with the infantile form do die of the disease, so do those with the juvenile form, making the disease equally lethal.
 
(E) Choice E states that it can be inferred that the causes of lysosomal storage diseases were unknown before the 1950s.  The passage states, however, that the causes of Tay-Sachs disease were unknown before that time. We do not have any information about the causes of lysosomal storage diseases generally.

Okay so all these answer choices except for C were wrong because they were taken from the Tay-Sachs passage which is only one type of lysosomal storage disease.

HOWEVER.... answer choice  C  ALSO takes information from the paragraph about Tay Sachs disease and applies it to the answer about lysosomal disease in general. So what the what????? I don't get it. The lines referred to in answer choice C refer to Tay Sachs disease.

Does anyone understand why C is correct and the other answer choices are not because they supposedly only talk about Tay Sachs disease?

Linhbiz · Answer

Let me try to exchange the idea by my own understanding after re-read the passage several time.

Sentence 6-11 said:

"When  any one of the lysosomal enzymes is defective , the molecules requiring that specific enzyme for their degradation will accumulate and cause that individual's lysosomes to swell enormously. The physiological effects of such swelling on the individual include  motor and mental deterioration , often to the point of  premature death ."

So the line of reasoning is that:

Any (>=1) LE failed --> swell enormously --> physiological effects...premature death:  sound pretty serious and fatal to me!

Answer choice C: 
C. They can be fatal even when allowing  some enzymatic activity.

Up to this point, it becomes very tricky because  "These enzymes do their work in the lysosome"  and you only get issue  "When any one of the lysosomal enzymes is defective"

But how do you define  "some enzymatic activity"  in this sense - since all the rest of the passages are only presented about TSD (not fully cover LSD), the best of my guest is that  some enzymatic activity also includes the defective enzyme's work/activity   as well.

Here is when the word "C. They   can   be fatal " is played its role here.

Voila, so there is a  possibility  that (by the word: CAN)  enzyme is defective and is active --> fatal.

Therefore,   C   - is the best choice out of 5.

Timebomb · Answer

Tough passage:

Can anyone explain the option choice D in question 1

workout   carcass

(D) Does the onset of other lysosomal storage diseases vary with the  location  of mutations in DNA sequences?

I just didnt mark this because of the word location.It is not dependent on location where the mutation is taking place but on the mutations themselves.

Can some one please clarify this.

Regards
Mudit

carcass · Answer

Hope is clear now why is D. It is a related chain.

Regards

harshbirajdar · Answer

11 mins - 1 correct 😂  brutal

ishwarSubra · Answer

Hi All,

I am confused by the explanation for question 2 and why that answer is (C). When doing this question I read that there "is little to no activity.." enzymatic activity in children. However, it also says kids " rarely  live beyond 3 years." What if the kids who had little enzymatic activity were the ones who rarely survived? I feel like I moved away from this answer precisely because I thought this was a trap related to the detail above.

If the passage had given us a firm statement that the juveniles (onset between 3-5) all had little enzymatic activity I would have totally picked (C) because the passage clearly state most of those kids only live to 15 (so most kids with little enzymatic activity died at 15). But the passage only talks about adults for whom the disease is not lethal.

Can someone please clarify? If there are Manhattan instructors who could explain as well that would be appreciated.

ishwarSubra · Answer

Ok so as I posted this I realized something, which is that it says adults " generally  live out a normal lifespan." So some could have passed away earlier with moderate impairment. I am now convinced (C) is correct, but not for the reasons stated in the official Manhattan guide. To me an inference is something that can be reasonably stated based on the information in the passage, and to use what is said about juveniles as sufficient to justify (C) seems incorrect.

UserMaple5 · Answer

For question 1, I understand why D is right but I don't understand why B is wrong. Can someone please explain? I was really torn between these two answer choices.

Thanks

Sajjad1994 · Answer

Read the detailed explanation in the post in the link below https://gmatclub.com/forum/lysosomal-st ... ml#p800806

Lysosomal storage diseases form a category of genetic disorders result

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GMAT Reading Comprehension (RC) Questions

Lysosomal storage diseases form a category of genetic disorders result

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