MGMAT RC

[Guest]

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.



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

They are generally caused by mutations to the hexosaminidase gene.

They are undetectable until physical symptoms are present.

They can be fatal even when allowing some enzymatic activity.

They are most lethal when onset is in a patient's infancy.

Their causes were unknown before the 1950s.


Ans is C.

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).

I chose E. However E is wrong since we cannot generalize one disease for all of them. Aren't we doing the same thing in C?

[esledge]

Hmm, I answered this one for myself without looking at the explanation, and came up with different proof sentences. From the first paragraph, sentences 4 and 5:

"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."
(Emphasis added)

(C) is correct because it is basically a restatement of the bolded text above: "They can be fatal (i.e. premature death) even when allowing some enzymatic activity (i.e. one defective enzyme = others that function)."

It's worth noting that I did not look at the choices first--I went to the passage first, looking for where "lysomal storage diseases" were discussed most generally. I stopped reading at paragraph 2, agreeing with you that the second paragraph is about a specific case, Tay-Sachs.

Thanks for the question; I am going to suggest that the explanation be revised.

[Guuuueeessssttt]

Emily,
This question still shows incorrect explanation.
If C is correct, so should D be. Please update the database.

[jonathanc]

Emily, thanks for your explanation which is obviously much more satisfying than the correction provided online. I didn't have exactly the same than the previous poster, in mine it is written (I just paste it ) :

"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 [with the infantile form of the disease] rarely live beyond 3 years old." "Little... activity," while low, is still not zero activity. "

Thanks, to update the base when some explanations are a little bit unsounded, it is the second time in two tests that I am encountering comprehension difficulties in the RC explanations.

[RonPurewal]

Emily, thanks for your explanation which is obviously much more satisfying than the correction provided online. I didn't have exactly the same than the previous poster, in mine it is written (I just paste it ) :

"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 [with the infantile form of the disease] rarely live beyond 3 years old." "Little... activity," while low, is still not zero activity. "

Thanks, to update the base when some explanations are a little bit unsounded, it is the second time in two tests that I am encountering comprehension difficulties in the RC explanations.

feel free to continue posting your issues with the practice tests as well. any improvement we can make, we want to make.

[vcb_007]

It seems that the updation is not yet done in the on line explanation .

I was not convinced of the on line explanation and then I refer to this site for explanation ( if any ) and found the one given is more convincing .

[vijaykumar.kondepudi]

Hi,
The current version of the RC is a slightly different from the one pasted in this thread.
I am still unable to understand why can't "D" be the right answer.

D. They are most lethal when onset is in a patient's infancy.

The introductory paragraph says that,

"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. 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."

And the 2nd para on Tay-sachs disease says,

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.
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.

Can't we conclude based on the bold-faced lines that the disease in more lethal in infantile group.

By the way, what does the term "more lethal" mean? Does it mean that there is little time between symtoms and the death.
Please clarify.
Thanks.

######################################################

Hmm, I answered this one for myself without looking at the explanation, and came up with different proof sentences. From the first paragraph, sentences 4 and 5:

"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."
(Emphasis added)

(C) is correct because it is basically a restatement of the bolded text above: "They can be fatal (i.e. premature death) even when allowing some enzymatic activity (i.e. one defective enzyme = others that function)."

It's worth noting that I did not look at the choices first--I went to the passage first, looking for where "lysomal storage diseases" were discussed most generally. I stopped reading at paragraph 2, agreeing with you that the second paragraph is about a specific case, Tay-Sachs.

Thanks for the question; I am going to suggest that the explanation be revised.

[RonPurewal]

Hi,
The current version of the RC is a slightly different from the one pasted in this thread.
I am still unable to understand why can't "D" be the right answer.

D. They are most lethal when onset is in a patient's infancy.

The introductory paragraph says that,

"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. 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."

please don't quote so much unnecessary material; when you do, it takes several reads to figure out which part of your post is the actual question.

you're misreading the phrase "premature death"; you're assuming that this must refer to the death of babies. that's not the case; "premature death" refers to any death that occurs earlier than normal (i.e., before death would be caused by normal processes of aging and senescence).
this point is underscored by the following paragraph, which documents deaths from these diseases the in varying ages of people. (ironically, you quoted that part of the passage yourself.) that part alone is enough to disprove the thesis that this disease has any mandatory connection with infancy.

[shanazarov]

Emily,

With all due respect, I think there is a mistake in your explanation.

"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.

(C) is correct because it is basically a restatement of the bolded text above: "They can be fatal (i.e. premature death) even when allowing some enzymatic activity (i.e. one defective enzyme = others that function)."

In the part of the passage above, that you are linking to the answer choice, "any one" refers to the type of enzyme (not to the units of enzyme) For example, in case of Tay-Sachs disease, this one enzyme is hexosaminidase.

The passage further describes, that mutation level of the specific enzyme results in different activity levels of this specific enzyme.

"Some enzymatic activity" in the answer choice C, refers to activity level of one specific enzyme.

(i.e. one defective enzyme = others that function)."

Thus becomes irrelevant - since we are talking about one and only one enzyme, and its activity level.

In essence, that part of the passage tells nothing about activity levels of the enzyme.

[tim]

Sorry, there is nothing in the question or in answer choice C that restricts our discussion to a single enzyme. Please read the information more carefully, and let us know if you still have a question..

[kre]

I understand the point around why C is being shown as correct, although I'm not sold that answer E can't be correctly inferred from the passage also.

On Line 20, first paragraph, it states:

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.

The passage later tells that this analysis began in the 1960s and did not result in root cause until the 1980s. Why wouldn't we infer that the cause was not known prior to the 1950s? Isn't it explicitly stated that Tay-Sachs was the first disease studied, and the cause of Tay-Sachs was not known until well after the 1950s?

[thulsy]

regarding why Choice (E) is incorrect, here's my view - different from that provided by OE. Comments are welcome.

Choice (E) says "Their causes were unknown before the 1950s."

However, paragraph #1 says (here's my notes):
LS disease caused by defective enzyme (detail)
... highly variable ----> variability puzzled, only recently solved

In other words, the bulk of the 1st part already explains the cause of the LS disease, and the 2nd part says the mechanism of variability was unknown (before the 1950s), not the cause itself was unknown. Therefore (E) is incorrect.

[tim]

thanks. let us know if there are any further questions on this one..

[rte.sushil]

I saw the revised explantion for answer C, which states:

(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 [with the infantile form of the disease] rarely live beyond 3 years old." "Little... activity," while low, is still not zero activity.


statement in the explanation""those in the infantile category had little to no normal activity"" , cann't it means that since there was no activity so it was fatal? because they had mentioned word "HAD"

So in the option C, They can be fatal even when allowing some enzymatic activity....

combining above 2 statements, how can one conclude that since they had little activity so allowing some more activity can also be fatal? may be i am missing something in understanding:(

[tim]

this has nothing to do with "allowing some more activity". there is already some possibility of activity when they say "little to no activity"..