Alfie was born on the 27th March 2021, in Frimley Hospital, UK. Unlike his older sister Lola, there were a few things that were flagged during the pregnancy, notably polyhydramnios - where there was too much amniotic fluid around the baby. This was subsequently identified as Jess having gestational diabetes and quickly cleared up following a strict diet. Also, one of the scans didn't clearly show Alfie's stomach containing fluid, which may indicate a lack of connection with the throat. However following birth, the nurses quickly inserted a tube into his stomach and all was fine.
At birth there were a couple of similarities noted with Lola - he also had talipes, was breathing quite quickly and he was very quiet and floppy. However, 24 hours later Alfie was crying, going to the toilet and felt much stronger, so he was given the green light and soon discharged from hospital.
The following 10 weeks seemed perfectly normal, although we were very nervous about Alfie hitting his milestones given that his sister Lola never did. There was nothing flagged at Alfie's 10 week check with the GP, but at 12 weeks the care worker noted she was concerned about Alfie's lack of head control and tone. Then, at three months, he had his first seizure and was rushed to hospital. We found that he had a raging fever (over 40 degrees) so we were praying that it was just a febrile seizure, however Alfie very soon after started having the same 'twitches' as Lola and there was no denying there were a lot of similarities between them both.
Alfie is now 18 months old and he is suffering from anywhere between 80-100 twitches every day, which can very quickly cluster and go into a prolonged tonic clonic seizure. These are exactly the same twitches that Lola had.
Despite the similarity in his seizures and overall tone, Alfie's development has been slightly more progressive and his vision and hearing is more advanced than Lola's ever was. He's able to make some eye contact, he smiles and laughs every day and has now started using his arms more, responding to stimulation triggers, such as toys and sounds. He absolutely loves it when his sister Daisy sings to him and it always calms him down if he's upset.
Alfie's feeding is very up and down depending on how many seizures he's having and his weight gain has been very slow. Thankfully he's not needed a feeding tube and he is taking some pureed foods. We've not been able to get his seizures under control yet and are still trialling different AEDs to try and get some stability. Unfortunately steroids didn't have the same magical impact as they did on Lola and he doesn't get the same break from seizures when he's ill, although they are less frequent. Sometimes we're able to calm down the clusters with some ibuprofen, but Buccal Midazolam is the only medication that works in giving him a break from the twitches. His key triggers are any kind of temperature or illness, and teething. When he's having a break from the seizures he's like a different child - so strong, responsive and happy. He's got such a cheeky character and just loves to be cuddled and splash in the bath. This gives us hope that he will thrive with his development when we're able to stop these devastating twitching episodes.
It is only through everything we've experienced with Lola that we've been able to keep Alfie safe at home and out of hospital, but we know that this isn't the case for many of our other CRELD1 families. We continue to fight for Alfie and pray that we'll be able to stop the seizures and give him a better quality of life.
Alfie's genetics results
Sequencing analysis has shown that both copies of the CRELD1 gene has a variant that is predicted to affect the function of the CRELD1 protein.
The first variant, c.575G>A p.(Cys192Tyr), changes a single amino acid in the CRELD1 protein sequence. This variant is rare in population databases, is predicted to have a damaging effect on the protein, and has been seen in combination with a second damaging variant in a similarly affected patient (PMID: 32437232 and unpublished data). This variant is therefore likely to be disease causing.
The second variant, c.1128_1129delTG p.(Ala377ThrfsTer7), deletes two nucleotides from the DNA sequence and is called a frameshift variant. This is predicted to create a shorter CRELD1 protein product which is likely to impact the function of the protein. This variant is very rare in population databases and has been seen in combination with a second damaging variant in a similarly affected patient (unpublished data). This variant is therefore likely to be disease causing.