Lysosomal storage diseases form a category of genetic disorders result

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.