We got Giuliana’s genetic test results back in April but I haven’t been ready to post about them until now. Giuliana has been diagnosed with a rare mitochondrial disorder called Leigh Syndrome. Leigh Syndrome is a fatal neurodegenerative disorder that currently has no cure. Obviously, the diagnosis is devastating for us but we are focusing on enjoying the time we have with our beautiful daughter and giving her the best life possible.
Leigh Syndrome actually has about 200 known genetic causes and there are still many genetic causes that have not yet been discovered. In order to identify the genetic cause of Giuliana’s disease, she had a dual genome test done that examined a total of 199 genes that are known to cause Leigh Syndrome. Her doctor told us that there was a possibility that her genetic cause was something that had never been seen before in which case she would have to have more genetic testing done. We were relieved that her testing did reveal a genetic cause because we know that so many families never find the genetic cause of their child’s disease and not knowing is torture. Giuliana has a mutation in each copy of a gene called NDUFS8. There have only been 10 published cases of children with mutations in that specific gene although there probably have been more that were not published or were never diagnosed (since genetic testing for these types of disorders has only started within the last 5 years). The NDUFS8 gene itself codes for a protein that is part of an enzyme called Complex I. The Complex I enzyme is the first enzyme in a chain of 5 enzymes that the mitochondria use to produce energy, There are over 45 genes that are needed to produce Complex I (it’s one of the largest enzymes in the body) and Giuliana has a mutation in one of them but that’s enough to make her enzyme ineffective and to make her very sick.
Giuliana’s disease is a recessive disorder meaning that she inherited one mutation from me and one from her father making her father and I both carriers of the disease. Everyone is a carrier of several recessive disorders, however both parents have to be carriers of the same disorder for their child to have the disease. And even if both parents are carriers of the same disorder there is only a 25% chance that the child will inherit the disease. Unfortunately, her father and I both happen to be carriers of this very rare disorder and Giuliana fell in that 25% that inherit both mutations and have the disease. There are carrier tests that can be done to determine if someone is a carrier of a disease which her father and I did take. However, even the most comprehensive carrier screening only tests for the 200 most common genes to be carriers of and NDUFS8, Giuliana’s gene, is not one of them. Doctors know of at least 800 genes that can cause fatal recessive disorders but only the most common are screened for. Therefore, there was no way for us to have known that we were carriers before having Giuliana. The only way someone finds out that they are a carrier for something so rare is if they have an affected child. Because being a carrier in the NDUFS8 gene is so rare, doctors can’t tell us exactly how many people are carriers in that gene. They have given us estimates of anywhere between 1 in 100,000 to 1 in 1,000,000 people could be carriers. To put that in perspective about 1 in 30 Caucasians are carriers for cystic fibrosis which is also inherited in a recessive manner. The odds that we are both carriers of something so rare is hard to wrap our minds around but sadly it is our reality.
So for now we are focusing on our time with Giuliana. Despite her medical diagnosis Giuliana is an extremely happy little girl. Her smile and laughter brings joy to our hearts. She has taught us so much and brought us so much happiness. I love being her mom and am so happy to have her in my life. I treasure every moment I have with her. She will always be a blessing to me.
On September 27, 2014 Giuliana and her family will be participating in the Energy for Life Walk to help raise money to find a cure and treatment for Leigh Syndrome and other mitochondrial disorders. You can support Giuliana by donating directly to the United Mitochondrial Disease Foundation on Giuliana’s team page. Thank you in advance for your support.
First of all I would like to thank everyone for all their support. I created this blog to try to find someone to save my daughter and I have received an outpouring of support from family, friends and complete strangers that has truly renewed my faith in people. I am so touched that so many people want to help Giuliana which has helped me get through some of the most difficult times.
Because of everyone’s help and connections we were able to get Giuliana an appointment with Dr. Falk at CHOP in mid December. Dr. Falk is an expert in the field of mitochondrial genetics and from the moment we met her I had complete confidence that she will be able to find out what is wrong with Giuliana. This first appointment was extremely overwhelming because although I knew how serious Giuliana’s situation is, it was very difficult to hear. Dr. Falk explained that people with mitochondrial and metabolic disorders have certain “triggers,” including illness, which cause them to deteriorate because when stressed their systems can not meet the demands to function normally. They suffer from “metabolic strokes” which cause neurological impairments. That is why Giuliana regressed so rapidly when she got a very high fever in early December.
Dr. Falk gave us the best and worst case scenarios which I wasn’t prepared for. Although I knew that Giuliana would have to see some specialists, I didn’t expect the extensive list (ophthalmologist, neurologist, cardiologist, audiologist, gastroenterologist, physical therapist, occupational therapist, and even a special pediatrician for complicated cases). Basically, because every cell in the body has mitochondria, any organ or system in the body could be affected. So Giuliana has to be evaluated by all these specialists in order to determine what has been affected. Basically we have spent the last 7 weeks going to all these appointments and luckily most have had fairly good news. Even the ophthalmologist said that Giuliana’s retina is anatomically and functionally normal and that she sees fairly well despite the nystagmus. Dr. Falk also felt that Giuliana was alert and was pleased with her overall growth. Her length and weight are both around the 10th percentile but her weight is good for her length. Also her head size is actually in the 25th percentile so overall she is proportionate.
Dr. Falk basically told us there are hundreds of diseases, both metabolic and mitochondrial, that could cause Giuliana’s symptoms. Therefore, she recommended doing genetic testing for all possible causes. She recommended not doing the muscle biopsy at this time because she felt that it was likely that Giuliana’s diagnosis could be found with genetic testing which is obviously less invasive. We have begun the genetic testing but it takes several months for the results so we probably won’t have a definitive diagnosis until April. There is also the possibility that the genetic testing won’t reveal a diagnosis and then at that point we would have to do the muscle biopsy. We are praying that Giuliana’s disease is found through the genetic testing and that her condition can be treated because unfortunately many of these disorders have no treatment or cures.
Dr. Falk also started Giuliana on a vitamin cocktail which consists of vitamins and enzymes that may help some patients with mitochondrial diseases. Since starting the medicine we have seen some improvement in Giuliana. Her skills still fluctuate a lot and she has good and bad days but she is doing better than in December. We know the road ahead is long, hard and uncertain but we remain hopeful.
Our Best Gift Ever – December 29, 2013
Giuliana was released from the hospital today. But it’s only a brief respite before she goes for more tests. Her family and friends have been talking to doctors in the US. The doctors in Italy have cleared Giuliana for flight, so soon, she’ll be in the states for the first time.
Preliminary results from the MRI indicate the possibility of mitochondrial disease based on
higher than average lactate levels. The mitochondria are the parts of the cell that generate energy for the cells.
The next step is to have a cell biopsy (usually taken from the muscle). Doctors will then analyze the mitochondria cells to try to figure out the specific disease and a treatment if possible.
Gianna and Enzo will return to the United States with Giuliana for treatment.
Today Giuliana had an MRI with spectroscopy (no contrast). We should get the results late today or tomorrow along with metabolic blood test results.