Alice DOB 11.2.2006
Alice is the second child of Nicole and Michael, and is one of only three female children diagnosed in Australia with CDKL5. This is a rare genetic condition with no known cause or cure. Alice’s prognosis is one of ongoing intellectual and physical disability, severe gut dysfunction and uncontrollable seizures, which are reported to be the most likely cause of a premature death.
I would like to present a succinct summary of Alice’s life thus far.
Alice was first thought to have developed seizures at 8 weeks of age. On presentation her symptoms were as follows:-
· Staring episodes associated with blinking eyes
· Rigid body and jerking movements
· Arching of the body
· Head lag
· Colic
In May 2006, at 13 weeks of age Alice was transferred from Hobart, Tasmania, Australia to the Royal Children’s Hospital in Melbourne, Australia, under the care of Dr Simon Harvey, Director of Children’s Epilepsy Program (RCH) Children’s Neuroscience Centre.
Alice had the following investigations:-
· MRI scan - normal
· Ophthalmological investigations - normal
· Video EEG - confirmed seizure activity
· Metabolic tests
Alice returned to Tasmania on a cocktail of medication: phenytoin, omeprazole, midazolam, and the formula Neocate. She returned to Melbourne in August for further intensive investigation which included samples taken for: glucose lactate, pyruvate and amino acids. Samples for protein and CSF neurotransmitters were also done together with bloods for UEC, LFT, B12, folate, VLCFA, mtDNA, and poLG. Skin biopsies were taken for EM and fibroblast culture and, a urine sample sent for amino acids and organic acids.
There were no clues as to the aetiology of Alice’s seizures from the history or examination, and at this stage Alice appeared developmentally normal. There was no evidence of an under-lying cerebral abnormality or metabolic disturbance. It was stated that Alice’s case was very difficult, and she was discharged home. Alice developed increasing hypotonia and gastrointestinal disturbance. She did not feed well and had intermittent coughing and spluttering that correlated with her drowsiness. She had foul smelling bowel motions and straining, often associated with increased seizure activity. Further investigations followed which are too numerous to list in this short summary. Alice was commenced on more medication in August 2006. By this stage Alice’s mother, Nicole was convinced there was a connection between Alice’s seizure activity and ongoing gut disturbance.
Nicole initially presented Alice to my sister, Dr Jane Chapman in October 2006. It was clear that Alice needed intensive investigation for her brain-gut connection dysfunction. Alice had numerous investigations including hair tissue mineral analysis, whole blood copper levels, whole blood zinc levels, food IgG antibody levels, and faecal microbiology investigations. Other investigations included amino/fatty acid blood tests and a range of conventional blood tests, resulting in numerous abnormalities being reported.
By May 2007 I was treating Alice with numerous nutritional supplements. I suggested a consultation with Dr Jacques Duff may be of assistance and Nicole and I went to Melbourne to attend a weekend lecture regarding the brain-gut connection where he was presenting. At this time Alice was having up to 30 seizures a day, awake or asleep, accompanied by screaming, especially when she was starting to come out of a seizure or attempting a bowel motion. Alice experienced extreme straining at times when passing stools; which were often jelly-like in consistency, putrid foul smelling, marbled black/green containing mucous, and often occurring directly before or after seizure activity.
Alice was assessed at the Austin Health Comprehensive Epilepsy Unit by Professor Ingrid Scheffer (Paediatric Neurologist), and it was decided that her epilepsy was likely to be a generalised process without a surgically amenable focus. The Ketogenic diet was discussed, according to Professor Scheffer’s advice, with the Ketogenic Diet Team and it was decided to commence this diet.
By November 2007 Professor Scheffer had completed a thorough assessment of Alice. By this time Alice has undergone 3 MRI scans which were all normal. Alice was now 21 months old and Professor Scheffer thought there was a genetic basis to Alice’s disorder. Rett Syndrome features were identified, although Alice did not have all the typical features.
It was discovered that testing for CDKL5 could be sourced through the United States. Epilepsy genetic researchers helped facilitate this investigation. Further exploration of the possibility of surgery was discussed but seemed extremely unlikely as numerous EEG, MRI studies, and PET scans showed no focal features to suggest a lesion in the brain that could be resected.
The Ketogenic Diet was adhered to thoroughly by Nicole; however there was no improvement, in Alice’s condition, on the diet. By May 2008 Alice had commenced on a wheat and dairy free diet, with ongoing supplements, and was becoming more alert and interactive.
At age 2 ½ yrs Alice was having 1 seizure a week. At that stage there were no bowel problems and Alice was on a number of specifically selected supplements. At 2 yrs 8mths Alice was on a diet excluding yeast, soy, gluten and dairy, and avoiding artificial colours and flavours. Her well being was improved with rare vomiting. Alice looked happier and healthier and her weight was 13kg. Supplements Alice was taking included Calcium, Multi Flora, multi-vitamins and 5HTP. Alice’s emergency medication was midazolam, given by intranasal or buccal administration only for clusters of seizures or seizures with breath holding or of increased duration.
At this time a laboratory result from Paris showed Alice had a likely mutation of the gene CDKL5. This gene has only been found in the last 4 to 5 years; therefore the future of Alice’s condition is unknown. The risk of death with this type of epilepsy is understood to be at least 25% mortality by age 20 but the figures specifically are unknown as there are only 60-70 children diagnosed worldwide.
I received correspondence from Professor Ingrid Scheffer in April 2009. Alice is now 3yrs 2 mths old. She is making definite developmental progress and had an amazing 211 days without seizures until March 2009. Her seizures have reoccurred which Nicole attributes to a slight change in Alice’s diet. Alice was having almond meal, wheat and dairy and had 5 seizures in the week beginning 23 March 2009. Since then these allergens have been removed from her diet and Alice has had one or two mild seizures per week. Alice’s bowels are not yet as regular as in her seizure free period.
Alice remains on no anti-epileptic therapy. She is on a variety of treatments including Calcium, Multi-flora, multi-vitamins, 5HTP, doses of pure fish oils and amino acids.
Alice has a de novo change as neither Mike nor Nicole carry the gene mutation found in Alice.
Nicole will attend a conference in Milan in June 2009 on CDKL5 disorders. Nicole has found that generally all the children suffering from CDKL5 disorder have gastrointestinal difficulties.
Alice now weighs over 14kg, is crawling and is nearly able to stand. Alice is also starting to use her hands more functionally.
I look forward to watching and assisting beautiful Alice’s progress through life.
Dr Sally Chapman
MBBS, FRACGP, MACNEM
7 May 2009
Currently Alice's diet is: Dairy free, gluten and soy free, free of artificial colours and flavours and... we have to be careful with just about everything else she eats. Red meat makes Alice vomit, peas turn her bowel motions to liquid acid and apricots send her seizures out of control (to list a few). Testing has highlighted dairy as a food Alice will probably never tolerate (it's like giving her arsenic) but, hopefully, as Alice's gut health improves she will be able to tolerate a wider range of foods.
