This is part of our House MD Project series.

Click here to read the connection to the episode (spoiler alert!)


On episode 15 of season 1, called Mob Rules, a mobster named Joey arrives at the hospital with a coma, from which he comes in and out to repeatedly. It turns out Joey has ornithine transcarbamylase deficiency, a disease causing him to not being able to digest red meat. On a side note the team also discover he has hepatitis C (an infection transferred either by needle sharing or homosexual activity) and that he has a high estrogen level in his blood, caused from a drug used to suppress libido. The last two facts lead house to the conclusion that he is also gay.

Danger level: High

What is it?

Ornithine transcarbamylase deficiency (OTD) is a rare genetic disorder causing a problem with eating protein.

Who gets it?

OTD is a rare condition – it affects about 1 in every 80,000 people. The condition is genetic, meaning it is passed on in families. It also usually happens to males, due to the mode it is inherited.

Usually the condition becomes apparent in the first few days of life. Sometimes, though (like in the House episode), the condition can manifest later in life.

What causes it?

We live and function thanks to millions of reactions that happen in our body each day. One of those reactions happen inside a cycle of reactions called the urea cycle.

The urea cycle. Drawing by Yikrazuul

The urea cycle is a sequence of reactions that happen in our liver cells. It processes excess nitrogen, which is generated when our body uses protein. In order to get rid of the excess nitrogen, the cycle turns it into urea, which the kidneys can get rid of in our urine.

Each of the steps in the cycle happens through the action of a special machine, called an enzyme. In OTD, one of those enzymes is damaged or missing. Since the body can’t get rid of the excess nitrogen, it is accumulated in the body, turning into a dangerous substance called ammonia.

Ammonia is dangerous for our nervous system and so the condition causes neurological problems. The excess can also damage the liver.

How does it feel?

The condition, as we mentioned above, usually becomes evident in the first days of life. The baby will be lacking energy, vomit, or refuse to eat. Its breathing rate and body temperature will be poorly controlled. Sometimes seizures can occur, and even a coma is possible.

In adults the symptoms aren’t very different. They can include loss of appetite, irritability, heavy or rapid breathing, weakness, vomiting, disorientation, sleepiness, and also coma and death. (Remember that the guy on the House episode had recurrent comas).

How is it discovered?

A blood test is done which shows that the person has too much ammonia in their blood. There’s also a test done on a urine sample that can give a clue to the condition.

Also, a genetic test can find out if the person has the defective gene (although it doesn’t work all the time).

How is it treated?

Since the body can’t handle large amounts of nitrogen (it can’t turn it into urea like it normally should), the treatment includes measures that lower the amount of nitrogen in the body.

This includes not eating lots of nitrogen (protein is very nitrogen-rich. That is why a low-protein diet is subscribed. Remember the mobster in the House episode couldn’t eat steaks?).

Treatment includes saying goodbye to steaks. Photo by FotoosVanRobin

Treatment also includes lots of food and water when a person is ill (since otherwise the body tends to break down its own protein at these times) and some medications that can lower the nitrogen in the body.

What happens after treatment?

The baby’s brain can be damaged from the disease (by the ammonia) if not treated on time. It’s important to catch the disease on time, and then to keep with the strict diet throughout life.

The bottom line – How do I avoid it?

As with other inherited diseases, you can’t really prevent it once the person is born with a defective gene. Parents that know they carry the defective gene and can transfer it to their children can use genetic testing to test if the developing embryo has the defective gene (a process called preimplantation genetic diagnosis).

Related posts:

1. Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency – When Certain Conditions Can Destroy Blood Cells
2. Iron Deficiency Anemia – A Common Type of Anemia
3. Toad Venom Poisoning – If You Eat Certain Sea Foods You’d Better Read This (As Seen on House MD)

After a long break, Grey’s Anatomy has returned last night, and with it this column covering a disease seen in the last episode. Today’s disease is Tay-Sachs.

Danger level: High

What is it?

Tay-Sachs disease is a rare disorder in which fat accumulates and damages the brain.

Who gets it?

Tay-Sachs is more common in Ashkenazi Jews (before screening tests were started, about 1 out of every 3000 newborns was affected by the disease). It’s also common in Louisiana Cajuns, Pennsylvania Dutch and French Canadians. In other populations it’s much rarer, and occurs in about 1 out of 300,000 newborns.

The disease affects boys and girls to the same extent.

It has 3 forms, each one manifesting at a different age:

1. Classic infantile acute form – Starts at 4-8 months of age. This is the most common type.
2. Late infantile and juvenile subacute form – Starts at ages 2-10.
3. Adult chronic form – Can start anywhere between childhood and adulthood.

What causes it?

Our body produces an enzyme (a molecule that’s responsible for performing a job in the body) called hexosaminidase A. This enzyme is responsible for breaking down compounds made of fat in our body, named gangliosides. When gangliosides aren’t broken down, they accumulate in the nerve cells in the brain causing them to die. In Tay-Sachs disease there is a problem with the enzyme hexosaminidase A, causing gangliosides to accumulate.

Tay-Sachs is a genetic disease, meaning that it runs in families. There are two ways in which genetic diseases can be transferred to children – recessive and dominant. Tay-Sachs is transferred in a recessive way. This means that both parents should have one defective gene in order for the child to get the disease. When both of the parents carry the defective gene, there’s a 25% chance for the child to get Tay-Sachs, as seen in this drawing:

The inheritance of Tay-Sachs disease. Both of the parents are “carriers” of the disease, meaning 1 out of possible 2 genes are defective (if 2 of them were bad, they would have the disease themselves). The child on the right got 2 defective genes – one from each parent, and has the disease. Photo by Cburnett

How does it feel?

Babies with Tay-Sachs appear healthy at birth, but in 3-6 months after birth they start having weakness, or difficulty with movement. They also start having twitches in their eyes.

All patients with Tay-Sachs also have a “cherry-red” spot in the back of their eyes (only visible through am ophthalmoscope):

Everyone who has a child or has followed one since birth know that in the first months and years of life they learn to do different things, such as hold things, crawl, walk. In Tay-Sachs, those things that they learned to do are lost, starting at age 6-10 months.

From there, the disease progresses to seizures, blindness, deafness, paralysis and difficulty with swallowing. These children usually die at age 4-5.

(Please note that, as stated above, there are 2 more, milder types of the disease, which aren’t covered here).

The following video shows Elise Ryne Rochman, who was born December 1, 2004, and diagnosed with Tay-Sachs on November 2005:

You can visit her website here.

How is it discovered?

A blood test that measures the level of the enzyme hexosaminidase A in the blood is performed, in which we will see a low level of the enzyme. To confirm, a genetic test may be done that will show the defective genes.

How is it treated?

Unfortunately, there is no cure for Tay-Sachs disease. Measures to control the symptoms are taken, which may help the child a little.

What happens after treatment?

As mentioned above, these children usually die by age 4-5.

If either you or your partner are Ashkenazi Jews, French Canadians or of Cajun descent, or you have a family history of Tay-Sachs, you should be tested to see if you’re a carrier for the defective gene. If you or your partner turn out positive, it’s important that both of you get tested (since both parents need to carry the gene in order for a child to be sick).

If both of you are carriers, you should consider genetic counseling, since there are ways to discover if the fetus has inherited the disease itself.

Related posts:

1. Cystic Fibrosis – A Dangerous Inherited Disease Causing Thick Secretions
2. Wilson Disease – The Copper Disease That Could Wreck Your Liver and Brain
3. Astrocytoma (Butterfly Tumor)–A Brain Tumor That Spreads To Both Sides (As Seen On Grey’s Anatomy)