It is unfathomable to determine the magnitude of loss of a loved one. Larice's mother, Janine, and her family have been very brave and strong to share their story. This story, as narrated by Janine, are just not mere words but this an exemplary Herculean odyssey that exemplifies valour, fortitude, determination, perseverance and persistence. This is about our extraordinary ASH1L Warrior, Larice.
PRE-BIRTH
I found out I was pregnant with Larice in June 2020. We were very excited to welcome a little girl after a rare and complicated ectopic pregnancy resulting in a laparotomy and loss of my left fallopian tube. Overall my pregnancy was uncomplicated. I was admitted once in October due to an irregular heart rhythm and fetal growth restriction. The physicians completed a fetal echocardiogram which was normal and I spent the next 6 weeks going for weekly non-stress tests.
On December 8th I went in for my regular non-stress test and was subsequently admitted due to a fetal tachycardia. While Larice appeared stable, they felt it best to admit me for monitoring and likely ant-arrhythmic therapy. Overnight, the nurse noticed an even stranger arrhythmia and called the obstetrician. They consulted via facetime with a fetal cardiologist who likewise couldn’t identify exactly what was going on with Larice’s heart. They decided to deliver via c-section. I was 32 weeks.
POST-BIRTH
Initially, Larice was diagnosed with an intractable supraventricular tachycardia. It did not respond to cardioversion or adenosine. Therefore, she was transferred via ground ambulance to Nemours Children’s Hospital in Wilmington. I was told she would likely not make it through her first night due to her low cardiac function and rhythm burden. They discussed the possibility of initiating ECMO. My doctor agreed to discharge me immediately so that I could be with her.
Larice made it through the first time and continued to surprise her care team for the next 9 months. She spent time intubated, on very little oxygen via nasal cannula and eventually received a tracheostomy once transferred to Children’s Hospital of Philadelphia in April 2021. While her irregular rhythms which would vary by the week captured the attention of Nemours’s CICU team, her chronic lung disease and pulmonary hypertension became the focus at CHOP. While at Nemours, the electrophysiologist started Larice on amiodarone, propranolol, flecanaide, quinidine, lidocaine and the list goes on! A medication would look promising but then Larice would present with a different variation of the rhythm altogether. Remarkably, she remained hemodynamically stable.
In addition to her cardiac and respiratory issues, Larice struggled with feeding. Initially, we were optimistic as she took well to the bottle and pacifier. Soon, though, everyone noticed that GI transit and emptying were an issue. She underwent numerous GI studies. Nothing structurally wrong was ever found. However, she never resumed bottle feeds and only tolerated nutrition to her intestines.
GENETIC DIAGNOSIS
Genetic studies were done in the hopes of finding a gene mutation associated with an arrhythmia. The first round looked at a specific set of genes. She did have a mutation in the ANK2 gene which was a variant of uncertain significance with some preliminary evidence supporting a correlation with autosomal dominant long QT syndrome. We later discovered that she inherited this gene from her father. Clinical exome sequencing was later done which showed Larice to be heterozygous for a pathogenic variant in the ASH1l gene (c.6729dupA). This information confirmed my suspicion that Larice’s issues were due to more than her prematurity and rhythm burden.
AT CHOP
We made the decision to move her to CHOP in late March 2021 as she was not progressing at Nemours. CHOP was both closer to home and I thought we would benefit from a new set of eyes. The electrophysiologist was aggressive and quickly assessed that her pulmonary hypertension was not as severe as previously thought. She also was able to ablate some degree of the arrhythmia making Larice a suitable candidate for heart transplant.
Larice thrived at CHOP. As I mentioned, they trialed her on oxygen via nasal cannula and masks before intubating her again. It was determined that she required significant respiratory support (no one could say for how long) and so we moved forward with her tracheostomy in June 2021. This was life-changing for her. In addition, her condition stabilized enough that she was added to the heart transplant list officially that month. Larice, finally, was able to interact with her family and caregivers freely. She enjoyed music therapy, OT, PT, her toys, books, and music. She began to smile and reach for things. Her feeding really didn’t improve but she did start to gain weight. Larice struggled frequently with clotting and was on a steady regimen of lovenox. During this period, she was on Verapmil, I believe. She spent ample time in sinus rhythm which pleased her entire team. Likewise, her cardiac function was showing some improvement (it had never been too compromised). She did have some valve disease but not enough to intervene. In August, they made the decision to remove her from the transplant list as she was no longer sick enough to need a new heart. Finally, we started planning for discharge and imagining bringing her home!
We opted to get a GJ tube for feeding as she was still requiring feeds to her intestine. This was the final step before transitioning her to a progressive care unit before home. We were busy learning tracheostomy care, her medications, feeding regimens, mechanical ventilation, etc. Spending time with her was a joy as she was alert, happy, and alive after so many months of sedation and uncertainty.
I came to terms with her genetic mutation and was committed to giving her the best life possible. She moved to the progressive care unit on Tuesday, August 30th. I believed she would be home by Thanksgiving (given difficulties of finding home nursing). On Friday, September 3rd my mom stated that she had an amazing morning – interactive with the therapist, alert with great eye contact. That afternoon, she had a run of tachycardia. It resolved quickly. However, the team did not feel comfortable keeping her in the progressive care unity over the weekend. There were no beds in the cardiac intensive care unit, so she was moved to the pediatric intensive care unit. No changes were made to her medications, and she remained hemodynamically stable throughout the weekend with no additional arrhythmias. I noticed on Saturday and Sunday she was having more work of breathing but figured her hemoglobin may be low due to the repeated lab tests she was getting given the change on Friday. They assured me they would check I spoke to her CICU physician about finding her a bed there as soon as possible. She mentioned it was more likely she would go back to the progressive care unit but that everyone was watching her case carefully.
ANGELIC LARICE
On Monday, September 6th I spent the morning rocking her and listening to music. She seemed more uncomfortable when I would sit her up. I mentioned this to the nurse who said she would keep at eye on it. My mom came in the afternoon. She noticed the same thing but otherwise nothing that different. At about 4pm Larice started to gag and sweat. My mother and the nurse noticed the change. The team responded immediately. She had an acute event resulting in an asystole. They tried to resuscitate her with CPR but were unable. We chose not to do an autopsy. Our electrophysiologist said that she remained hemodynamically stable and there were no instances of arrhythmia. I imagine she sustained a pulmonary embolism given her increased work of breathing and pain at sitting up over the weekend. However, this is just a guess. Her death was devastating to our family and her providers. However, I do take comfort in the fact that she is not suffering. I am thankful to Mukti and the ASH1L families for their support during her short life.