Phenylketonuria

I love when everyday conversation leads to interesting medical facts. The other day at work, my friend Allie was reading her gum and noted the warning on the package, "Phenylketonurics: contains phenylalanine." From being a biochemistry major, I knew what phenylalanine was, but I had no idea what the word phenylketonuric meant, or what the warning was referring to. Allie looked it up, and hence I am doing this entry.

Let me break down what this warning means. A phenylketonuric is a person with phenylketonuria (PKU for short). phenyalanine is an amino acid that is often present in artificially sugary foods like diet soda and chewing gum. So the warning should be interpreted, "Hey you, this has that things that's bad for you." Or more analogously, "Hey guy who is allergic to peanuts, this is full of them".

Phenylketonuria is an autosomal recessive genetic disorder that renders sufferers unable to metabolize phenylalanine. I'm pretty excited that I get to reuse this genetic inheritance graphic. Something tells me the little girl on the bottom right isn't going to have a very fun time on this blog.

So what is phenylalanine? It's one of the essential amino acids. Whenever you see the word essential in front of something you eat, like essential vitamins and minerals, that means it is something you cannot synthesize yourself. Therefore, an essential amino acid is one you must have as part of your diet. Essentially, you need to eat it or you'll have problems. You can find phenylalanine in several places, including milk. Metabolically speaking phenyalanine, like most amino acids, can be used for many purposes. It is a precursor for tyrosine, another amino acid, which is then converted to L-DOPA for synthesis of dopamine, epinephrine, and norepinephrine.

So like most disorders that involve the inability to metabolize a certain compound, an enzyme deficiency is to blame. In this case phenylketonurics have a phenyalanine hydroxlase (PAH) deficiency. A hydroxylase is an enzyme that catalyzes the formation of a hydroxyl group (OH) through the addition of one or two oxygen molecules. This enzyme is responsible for converting phenylalanine to tyrosine. You can see from the illustration that tyrosine is identical to phenylalanine with the exception of the extra hydroxyl group.

Left unchecked, this disorder can lead to mental retardation and impaired brain development. Phenylalanine shares a transport pathway with tryptophan, the amino acid precursor to serotonin, and thus when levels of phenylalanine are high, it can interfere with metabolic activity in the brain. In early development, high levels of phenylalanine in the blood can saturate certain amino acid transporters leading to a decrease in the levels of other amino acids in the brain. Over time, this is what is responsible for diminished brain development.

That all being said, no one should really be afraid of these warnings on your gum package. Even if you have PKU, it's not a big deal from what I understand. Nowadays, early screenings can identify infants with PKU. So the disorder rarely goes unchecked. Treatments include a low-phenylalanine diet combined with protein supplements. In some cases, this treatment only has to be carried out through the first 16 years of an individuals life since the greatest danger of this disorder is apparent only during developmental years. So fear not phenylketonurics, that stick of gum probably won't turn your brain to mush.

Methemoglobinemia

I've always found the science of blood to be interesting, so for my first entry I decided to pick a blood disorder: Methemoglobinemia. That's pronounced, met·he·mo·glo·bi·ne·mi·a. Methemoglobinemia, aside from being a really neat word, is a blood disorder characterized by abnormally high levels of methemoglobin in the blood. Methemoglobin doesn't bind oxygen like normal hemoglobin does, thus tissues are deprived of oxygen. This lack of oxygen (tissue hypoxia) results in a markedly blue tint in individuals suffering from the disorder, thus the disorder's more commonly known name: blue skin disorder. This isn't nearly as sexy as Avatar would make it seem. Think more like, Violet Beauregarde from Willy Wonka and the chocolate factory. While not nearly as puffy, people with Methemoglobinemia often have blueberry-colored skin. 

So how does one get Methemoglobinemia? There are two ways: congenital and acquired. Congenital meaning you are born with it, and acquired mean you were unfortunate enough to get it all on your own. 


Those with congenital Methemoglobinemia, which I will henceforth abbreviate as met-Hb because I'm tired of staring at the long red scribbles on my computer screen, have a deficiency of diaphorase I. This is the enzyme responsible for converting methemoglobin to hemoglobin. Normal hemoglobin is red in color, whereas methemoglobin has brown tint. For people with lighter skin, this results in a blueish hue. There are a few other congenital causes involving hemoglobin malformations and other enzyme deficiencies, but this is probably the greatest congenital factor.


Let's take a quick look at the difference between a red blood cell (erythrocyte) with hemoglobin and a red blood cell with methemoglobin.

A molecule of hemoglobin has for subunits (two beta and two alpha) each with a heme group containing a ferrous iron molecule. Ferrous iron has a 2+ charge. In methemoglobin, the iron molecule is in its ferric state with a 3+ charge, making it unable to bind and transport oxygen. Now the illustration of the two erythrocytes is an exaggeration. You usually won't have a red blood cell composed entirely of one type of hemoglobin, as there are around 270 million hemoglobin molecules per red blood cell. Even a healthy individual will possess methemoglobin, though it is in levels below 1%. 


So for people with met-Hb, this disorder is caused by an autosomal recessive gene. Here's what that looks like in stick figure form.The "b" denotes the gene coding for the disorder, while the "B" denotes a healthy gene. (Also note that blue people aren't necessarily blue-skinned, they're just boys). Since it's recessive, the defective gene must be passed from both parents for the child to be affected by the disorder. Thusly, people can be carriers for the disorder without being affected by it themselves. 

Probably the most famous case of met-Hb is the Fugate family from the hills of Kentucky. I remember when I went to middle school in Frankfurt, KY, we had a reading prompt about them. In short, Mr. Fugate married Mrs. Fugate who was a carrier for the disorder. They intermarried with a nearby clan in the 1800's and bam, later generations of Fugate babies were blue. Probably the fastest way to cultivate recessive disorders is through inbreeding. From what I understand, it's why dalmatians are so screwy. 


Acquired met-Hb can be caused by a number of outside sources. Oxidizing drugs such as benzocaine (a topical anesthetic) and certain antibiotics, can interrupt the natural, protective enzyme pathway in blood, causing a large increase in the amount of methemoglobin. Nitrate compounds can also be a causative factor. In babies, nitrates consumed from drinking water can cause met-Hb, or blue-baby syndrome.


Luckily, for those unfortunate enough to resemble real-life smurfs, there are treatments for the disorder. The disorder can be treated with supplemental oxygen and methylene blue. Methylene blue is administered either intravenously or orally. It acts to restore ferrous iron to the blood, restoring its ability to bind oxygen.


So that was a lot longer than I anticipated it being, but I think I covered a decent amount of information. Hope you all learned something interesting. 

Howdy

Hey there folks. Welcome to my blog, illustrated medicine. I made this blog as an outlet for my two greatest passions: Medicine and Art. So what can you expect from such an awesome blog? Here, I will be posting entries about obscure, interesting, and educational medical facts. But that's not all. My posts will also have entertaining illustrations to go along with them. I think this will be a fun side project for me. Comment with any requests for entries. It could be a medical question, or maybe your favorite medical malady. I'm open to suggestions, so stay tuned for some exciting stuff.