Adrenoleuko-WHAT?

"What is Adrenoleukodystrophy, exactly?" That's the first question our friends and family want to know. We could point them to websites that give a general overview like this one  or we could point to more in-depth scientific articles like this one, but what they are usually looking for is a quick, bite-sized explaination. So,  we should go ahead and get that out of the way first thing. Adrenoleukosytrophy, or ALD, is a genetic disease caused by a mutation of the ABCD1 gene on the X chromosome. That sounds like we're about to launch into an episode of House, especially when it's said in the detached analytic tone I suddenly get when I start talking about the objective side of medical science. It's a pretty easy explanation  actually, and it only requires the most basic grasp of genetics. Do you remember biology class way back in high school or college? Remember drawing little squares that you filled up with lower case (recessive genes) and capital letters (dominant genes) to decide if Gregor Mendel's pea plants would be purple or white? How about the table you made to predict if some hypothetical baby would be blue eyed or brown haired depending on the genotype of its parents?

Yes? No? Ringing a bell? Now, think about the next (easier) part of inheritance you learned about, which was probably infinitely more interesting to you - meiosis (sex cell division) and baby making. What makes a lady zygote are two X chromosomes (XX). What makes a gentleman zygote is an X and a Y chromosome. (XY). When the mom's egg cells are made, they get one half of her genetic code in each cell. All that mom has to give are X chromosomes because she only has Xs. When the dad's sperm cells are made, each one gets half of his genetic code. Dad's cells are going to get either an X or a Y because he has one X and one Y. When the sperm and egg combine you have (Captain Planet!) a full genetic code for a baby:  Half are the dad's chromosomes and half are the mom's. Whether you have a boy or a girl, then, is entirely up to the daddy and which of his two chromosomes, the X or the Y, is inside the winner of this little swimming competition.

In this illustration, we're combining the two things we talked about above: Recessive genes and sex chromosomes. The mutation that causes Adrenoleukodystrophy is on the X chromosome. In this illustration, the affected X is colored red. A mother with one mutated X chromosome and one normal X chromosome, like me and the mother in the illustration, is called a carrier. She may show some symptoms of ALD, but these are usually mild and develop later in life. When she partners with a dad who has a normal X (i.e. does not have ALD), she has a 50/50 chance of passing the gene on to their offspring. Her daughters who inherit the mutated X chromosome will also be carriers. Boys with a mutated X have no other, normal, X chromosome to compensate for the damaged X (they only have one X and one Y), so they will have Adrenoleukodystrophy. Boys can not get ALD from their fathers because they got their X from Mom and their Y from Dad (if dad gave the X, he would be a she).

Adrenoleukodystrophy comes in a few different flavors. The childhood form is usually the most aggressive and Gabe is on the older end to be diagnosed with that as it usually is diagnosed between 4 and 10. The body is unable to break down very-long-chain-fatty-acids, leading to a build up of these substances that  cause a break down of the adrenals and the myelin sheaths of the nerves and brain. Untreated, or detected too late for treatment, this eventually will lead to a vegetative state and death. Other less aggressive forms might only attack only the adrenals or may attack the perpheral neurons, but might not attack the brain. Treatment during an early stage of this disease can halt the demyelinization and consists of bone marrow and stem cell transplants.  At this point, we don't know exactly what form of ALD Gabriel has. We are anxiously awaiting the results of his MRI to give us some indication as to the status of his brain. Gabe has an appointment on Thursday, February 28, to meet and be evaluated by his Bone Marrow Team at Duke.

From a human side, the outside, what does this actually look like? For Gabriel, it looked like a very small boy who never seemed to gain weight and was perpetually too short for the good rides at the fair or theme park, a great tan compared to the glow-in-the-dark complexions of the rest of the nuclear family, bouts with depression and anxiety, and increasing difficulty with ADHD symptoms. What finally led to his diagnosis looked like a very sudden and bad case of stomach flu. He wound up in the ER in an adrenal crisis: vomiting, weak, severely dehydrated, with ketotic hypoglycemia, a blood glucose around 30, an altered mental status, pale with blue lips and extremities, slow capillary refill, and having lost several pounds of water weight over the course of a day.

What does it look like from a parent's point of view? Terrifying. Like a giant hole of near-hopelessness. Like trying to be strong for your little boy while you just want to throw a giant screaming tantrum and cry yourself to oblivion. Like saying the rosary and "I love you" more than you've ever said anything before.