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Meet Shane.

Shane has a rare genetic disease called Infantile Liver Failure Syndrome Type 1.

 

Infantile Liver Failure Syndrome Type 1 (ILFS1)

Infantile Liver Failure Syndrome (ILFS1) is caused by a double recessive mutation of the LARS gene. It has been recently identified that the recessive mutations in the cytoplasmic leucyl-tRNA synthetase gene (LARS) cause a multi-system disorder involving infantile liver dysfunction and acute liver failure, anemia, decompensation with minor illness, developmental delay and in some cases, seizures and encephalopathy (see Casey et al 2012). This disorder is now referred to as Infantile Liver Failure Syndrome Type 1 (ILFS1). 

What We Know

There have been two studies (Casey et al 2012 & Casey et al 2015) written about ILFS1 which we have included on the resources section of this website. These studies identify patients with ILFS1 and list various findings in each of these patients. Mutations in eight cytoplasmic and ten mitochondrial aminoacyl tRNA synthetase (ARS) genes have been associated with a number of human disorders, mainly those with metabolic, neurological, mitochondrial and muscular involvement. There is one previous report of infantile liver failure syndrome due to mutations in methionyl-tRNA synthetase (MARS), now classified as ILFS2. ILFS1 and ILFS2 are similar except that interstitial lung disease is additionally present in ILFS2. LARS and MARS are the first two cytoplasmic amino-acyl tRNA synthetase genes to be associated with a hepatic disorder which may suggest an overlapping disease mechanism (Casey et al 2012; van Meel et al 2013).

What We Don't Know

The pathophysiology of ILFS1 is currently unknown. However, the LARS enzyme is responsible for incorporation of the amino acid leucine during protein polypeptide synthesis. It is therefore plausible that proteins with the highest percentage content of leucine, which are largely immune-related proteins, will be most severely affected if LARS is not functioning efficiently (Casey et al 2012). One possible theory is that when children with LARS mutations are ill, the requirement for leucine increases due to the induction of immunerelated pathways that involve proteins with high leucine content and the mutant LARS may not cope with this spike in demand. This effect would be further exacerbated by low protein intake, and hence low leucine intake, when the children are unwell.

Alternatively, the disease mechanism responsible for recurrent liver crises may relate to the fever associated with infection. It is possible that the mutant LARS enzyme is thermolabile; that means it may retain reduced functionality at body temperature but is destroyed at higher temperatures associated with fever. 

 
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Shane's Story

Shane is an amazing 4-year old boy who was previously diagnosed with Cerebral Palsy. He came into this world at Lucile Packard Children’s Hospital in Palo Alto, CA prematurely—only 32 weeks and weighing in at 2lbs 13oz. My wife, Nicole, was in a car accident on the San Francisco Bay Bridge when she was 26 weeks pregnant with Shane. She started having contractions and was shortly thereafter diagnosed with preeclampsia. After Shane was born, he spent three months in the NICU at Lucile Packard. He was released at the end of June of 2012.

Liver Failure

After being home for only three weeks, he gained six ounces in one day and had a distended belly. We took him back to Stanford to find out he had a blood infection. He was immediately treated and we thought everything was going to be ok. Unfortunately, his liver started failing and was unable to recover. Shane was in critical condition at the Stanford Pediatric Intensive Care Unit for two weeks. He was put on a ventilator and dialysis to help retain fluid and to help support his lung failure. He was immediately put on the top of the transplant donor list as a 1-A across the entire United States. We waited for five long days with no calls about potential donors. The doctors told us that Shane only had hours to live and they could not keep him on the ventilator. That next day we received a call from a potential donor in Ohio. Stanford arranged a private plane to evaluate a potential liver for Shane.  Our prayers were answered—everything was a perfect match. Due to Shane’s very small size and the donor's liver being much larger than necessary, doctors would only use ½ of the liver during transplantation. The surgery was to be one of the most risky liver transplants Lucile Packard Children’s Hospital had performed due to the size of Shane at the time.

On July 19th, 2012, Shane had the transplant and the procedure turned out absolutely amazing. The new liver was taking to Shane’s body and the stitching of his tiny vessels were holding up. He was in the Pediatric Intensive Care Unit for another six weeks before he was released home. We were so excited to finally have our beautiful baby boy at home with us for good. However, Shane had new challenges to face. Some of those include the failure to thrive, pancreatic insufficiency, developmental delays, and complex seizures.

Searching for Answers

Ever since Shane was born, we have been in search of answers. Nicole and I opted for every test that was available including biopsy testing on his liver and extensive genetic testing. Every test came back negative and left us thinking that we may never know what caused all of these challenges for our child. Shane has been fed through a feeding tube since birth because he has extreme oral aversion that prevents him from being able to swallow any food or liquid. Shane had his first seizure in January of 2013. The seizures became more complex and caused him to stop breathing on multiple occasions. We have been able to control his seizures at times with medication. Shane is making progress but his speech development and motor skills are delayed. He is non-verbal and cannot walk without the aid of a walker. 

Understanding ILFS1

In June of 2015, we received results from a new genetic test at Baylor (click here to read more) that showed Shane was a compound heterozygote for mutations in the LARS gene. Both my wife and myself are carriers for one mutation in this gene. Shane happened to inherit both mutations of this LARS gene. As mentioned earlier,  being a compound heterozygote for mutations in the LARS gene has shown to present many challenges early in life—liver failure, failure to thrive, renal tubulopathy, developmental delay, seizures, and anemia. All of which Shane has had since he was born. This very rare genetic disease is called “Infantile Liver Failure Syndrome Type 1 (ILFS1).” When we received the test results from Baylor, we were very thankful to finally have an answer. We actually first learned of this news only a few weeks before our second son, Nixon, was born and were told he would have a 25% chance of having this same genetic disease. Fortunately, Nixon does not have ILFS1 and we are very grateful.

Spread Awareness

Shane is currently enrolled in an educational program where he can grow and learn with other children who are faced with similar disabilities. Just recently, he has been making significant progress—even beginning to take some steps with a walker without assistance. Since this genetic disease is so rare, there is very little information that is available.  The geneticists at Stanford were only able to locate two journals written about ILFS1 (view the resource section). Nicole and I are confident there are other parents out there who have a child with similar issues to Shane, who are also searching for answers, and we want to help. In this spirit, we started the website to generate awareness for this rare disease and hope it brings parents with similar challenges together so everyone can support one another. Please help us spread the word to bring together resources that will improve the lives of children with ILFS1. We have started a Facebook Group (click here to join) and encourage you to join us in this effort. 

Thank You, Very Grateful

We wanted to thank everyone who has helped us along the way. We are so lucky and grateful to have such an amazing support group and medical team. We have so many people to thank; the doctors, nurses, teachers, caretakers, friends and family. We are very blessed and forever grateful for your dedication and support. We love each and everyone of you!

Thank you for taking the time to read Shane’s story!

The Stump Family—Rich, Nicole, Shane & Nixon