So what is LPIN1 then?….
Well, and please bear with me as I am a just a parent with GCSE (high school) biology and not a Doctor, LPIN1 is a rare and only recently discovered (2008) Inherited Metabolic Disease where problems with both copies of this gene (Phoebe had a mutation and a large deletion) cause recurrent & severe rhabdomyolysis in young children. As an inherited condition the deficiency is passed from parent to child. We are currently in the process of confirming that the mutation came from one of us and the deletion the other. When 2 carriers, like us (TBC) have a child there is a 1 in 4 chance of the child having LPIN1 deficiency.
What is Rhabdomyolysis?….
Rhabdomyolysis is literally melting or dissolution of the skeletal muscle, muscle cells become stressed and breakdown, leaking muscle protein, or “myoglobin” into the bloodstream with risk of kidney damage/failure.
What triggers the Rhabdomyolysis in children with LPIN1?…
There are many conditions which cause Rhabdomyolysis, but in the case of children with LPIN1, simple childhood fevers have been identified as the main trigger, virus receptors in children with this genetic condition are over active and while the body thinks it is kicking into defense mode and attacking foreign cells it is actually self destructing.. Other triggers could be excessive exercise or fasting & dehydration. Vomiting bugs were invariably a trigger for Phoebe. Febrile illness becomes less of an issue as children get older, we all know how children pick up everything and anything when they are little.
Treatment involves the IV administration of fluids and high caloric/high carb intake i.e. glucose. Phoebe’s emergency plan recommended regular snacks and meals and the use of a high glucose drink in the event of her feeling unwell or having an elevated temperature as a preventative measure so the body would use this energy rather than attacking itself.
In addition to the threat posed by the protein (myoglobin), there is also a risk of electrolyte imbalance. Electrolytes are chemicals, including calcium and potassium, in the body with many important functions from regulating your heartbeat to allowing muscles to contract so the body can move. An imbalance can lead to arrhythmia, an irregular heartbeat and ultimately heart failure. Phoebe died from Hyperkalemia, elevated potassium, which caused heart failure. This was driven by Rhabdomyolysis as a result of an LPIN1 genetic deficiency.
What are the warning signs / How did we discover Phoebe had LPIN1?….
Muscle pain, rigidity in the limbs and difficulties in moving are a key initial symptom. When Phoebe was 17 months old she was poorly with an ear infection and fever. We saw our GP but we just sensed there was something more seriously wrong with her; she was a chatty toddler and had become withdrawn and unresponsive. She also seemed to be in pain, especially when seated, bent at the waist. She couldn’t sit in her car seat. We took her to out of hours for a second opinion and from there we were rushed through A&E and onto the children’s ward at University Hospital South Manchester in Wythenshawe. They threw everything they could at her both antibiotic and antiviral and ran all manner of tests eventually discovering that the Creatine Kinase (CK) enzyme was significantly elevated, it peaked at around 250,000 whereas average levels are around the 1-200 mark. An elevated CK count is a key indicator of Rhabdomyolysis.
Dark or Cola coloured urine is also a key sign indicating the presence of protein/myoglobin. This suggests that Rhabdomyolysis is pretty advanced and urgent action is required.
Following this first episode and stay in hospital we were referred to Manchester Children’s hospital for further tests including a muscle biopsy. We eventually received a diagnosis. Her diagnosis was not straight forward though, at the time they only found the mutation in 1 copy of the gene but given the episode of Rhabdomyolysis they fairly certain that there must be an issue with the other copy. It was only after her death that the deletion was also found.
Do children with LPIN1 have any ongoing issues?….
Some do, some don’t. Before her first episode of Rhabdomyolysis and in between episodes, Phoebe appeared to be a normal and healthy child with bags of energy. She recovered quickly and had no evidence of kidney or muscle damage but this has been an issue for other children. In addition while Phoebe always seemed to have bags of energy, this does not seem to be the case for other children whose muscles have taken longer to recover and whose mobility has taken longer to return. Some children also have issues with fatigue.
So how rare is the condition?…
I am only aware of 3 other sufferers in the UK and a handful across the globe via the “Shine for Thomas” parents group http://www.shineforthomas.com.au Phoebe’s consultant felt that the incidence level may however eventually prove to be around 1/100,000 so while rare it may be more prevalent than it currently seems, so if any of the above resonates with you please take urgent action, the consequences can be life threateningly tragic…..