What is Oculocutaneous Albinism? (taking it to the next level)

(yeah, I know, it's been about 5 years... stuff has happened, I'll get to it)

About 5 years ago, when I was in process to adopt my now 6 year old daughter Fiona, I wrote a brief piece about albinism, which is Fiona's main "special need".  

She still doesn't look at the camera. Probably plotting something amazing.

I've learned a lot about albinism since then.  Fiona is in 1st grade at school and thriving like nobody's business.  Her spunk carries her where her vision does not.  She is extremely adept at using the technologies provided for her in her IEP (Individual Education Plan), such as her CCTV, slant board and dome magnifier. (some examples linked - not the actual models she uses)

Crazy hair day.  The pink actually made her blend in *better* at school. 
Important note: colored hair spray comes out.  Colored mousse does NOT.  

 She doesn't suffer socially either.  We can't go anywhere in the school, and hardly get through an errand of any kind without someone yelling "HI FIONA!!!"  Everyone loves her (with the possible exception of the mother of the toddler she keeps trying to pick up and walk off with... what the heck, child?)

We couldn't resist.  She LOVES Elsa.

So we have it all in hand?  Functionally, yes.  Fiona is legally considered "disabled", but she is far from handicapped.  She has all the tools she needs to get anywhere in life that she wants to.  And she wants to!  Especially if there's food involved.  The child is a bottomless pit.  

BUT - I love to learn.  I love to deepen and broaden my understanding of things, so settling for "she doesn't make melanin, something about an amino acid" wasn't cutting it for me.  

Shortly after Fiona arrived home, she saw a geneticist at Denver Children's Hospital International Adoption Clinic.  He confirmed that Fiona has Oculocutaneous Albinism (affecting eyes, skin and hair), probably type 1, probably subtype 1A. (the most "completely depigmented" variety)  The test to confirm this conclusively cost thousands, was not covered by insurance, and would basically give us "gee-whiz" information unless Fiona became adamant that she wanted to have (or avoid having) children with the same condition.  

(Interesting fact: both parents need to not only carry and pass on the gene for albinism in order for the child to get it, but it has to be the same type of albinism. An OCA1 parent and an OCA2 parent would have children who have normal pigmentation for their ethnicity, but would carry genes for both types.)

I'm now back in college, taking pre-nursing courses in preparation for starting at Beth-El College of Nursing (within UCCS) next year.  As part of an assignment for Anatomy and Physiology, I read an article (abstract here) published by a Japanese team back in 1989, in which they isolated the root cause of Oculocutaneous albinism.  In it, I was able to learn the actual molecular level mechanisms of OCA.  Frikkin exciting for me!  (That's not sarcastic, I really dig this stuff.)

HIGH SCHOOL BIOLOGY REVIEW

• Enzymes are proteins that do stuff (make stuff, break stuff down, change stuff into other stuff) in the body.
• Proteins are made of amino acids
• Instructions for making proteins are in your DNA

IF YOU LEARNED THIS IN HS, GOOD FOR YOU, BUT I DIDN'T

• When you need to make a protein, your DNA "unzips" in the section with those instructions, they are transcribed, copied, and used as a recipe to gather the amino acids that make up the protein.
• DNA nucleotides (the "rungs" on the double-helix "ladder") are represented by letters.  
• Every 3 letters makes up a "codon", which is the call-sign for a particular amino acid.
• Protein "recipes" start with a "start" codon, and end with a "stop" codon.  

So here's the short of what happens with OCA

In order to make melanin (the brown stuff that gives our hair, skin and eyes color), the amino acid Tyrosine is supposed to go through 3 conversions.  The enzyme TYR (tyrosinase) is responsible for two of those. 

The code for this enzyme TYR in people with OCA has a problem, though.  There is one extra letter - C - stuck in about 2/3 of the way through the instructions.  That not only shifts the whole thing down by one letter, but it also messes up the recipe.  Remember that every 3 letters makes up a codon, which is a "code" for start, stop, or an amino acid.  Well, in this case, the codons are scrambled because they got shifted down one space.  Wrong signals are given this way - and in this case the "stop" signal is given (accidentally) very shortly after this extra C.  Oops.  So the resulting TYR enzyme is short.  Not only that, but the instructions for TYR are supposed to build two copper-binding sites.  The shortened TYR has only one, as the other got cut off.  Oops again.  

(Dangit, Jim, I'm a doctor, not a geneticist! Speak English!)

Okay, okay... Imagine with me that you're building an airplane left to right.  I know it wouldn't happen that way, but stay with me.  

You start building:  left wing - check, cabin - check...  and the instructions end there.  You need TWO WINGS for this thing to fly, right?  Well, sorry, the instructions ended and you only get one.  HAVE FUN!  

It's kind of like that.  

Without BOTH copper sites, TYR doesn't work as an enzyme.  It's useless.  So tyrosine cannot become melanin, and my little girl cannot freckle or tan, and she glows in the dark. (Almost - it's not something you want to wake up to in the middle of the night.  She's the cutest thing in the world, but she scared the crap out of me standing silently next to the bed.) 

So there's a thing you know now.  Isn't biology amazing???