Every parent celebrates the milestones and the developmental skills acquired by their child while they are growing, but what if the child starts losing all acquired skills progressively and fails to recognize their loved ones?
Harley Bond, UK, forgot about his mother and father at the age of three, after which he was diagnosed with a rare form of childhood dementia.
Childhood dementia is a progressive neurodegenerative disorder of childhood. It is defined as a loss of developmental skills with a decline in neurocognition following a period of developmental progress.
Childhood dementia is progressive. (1) The child progressively loses skills already developed as the brain damage increases. The ability to read, write, communicate, and walk is lost progressively with the progression of the disease.
The estimated incidence of childhood dementia is one in every 2900 babies. It is caused by over 145 rare genetic disorders. The life expectancy for childhood dementia is estimated to be 28 years; however, half of all children with dementia die by the age of 10. (2)
Childhood dementia is caused by rare genetic disorders, including Niemann-Pick type C, Batten disease, Sanfilippo syndrome, Lafora disease, Hurler syndrome 72, and Alexander disease.
Broadly, it includes:
Inborn errors of metabolism
Lysosomal disorders
Mucopolysaccharidoses (Sanfilippo syndrome)
Peroxisomal disease
Neurodegeneration with brain iron accumulation (NBIA)
Leukodystrophy (3)
Loss of memory
Confusion
Disturbed sleep
Change in behavior
Emotional issues
Change in personality.
Trouble communicating, concentrating, and learning. (3)
"Childhood dementia is never normal in children. There has to be a specific reason for it. Childhood dementia disorders are uncommon. The causes could be chromosomal, metabolic, or genetic. There is a myth in the western world of 'anti-vaccinators', but vaccination as a cause of childhood dementia has not been scientifically proven," said the founder and CEO of MedBound, Dr. Munish Kumar, MD, an attending neonatologist.
On an Instagram social media account run by the name of @savingsadierae, Ashley and her sister are raising awareness about childhood dementia, Sanfilippo syndrome.
Ashley Haywood, from North Carolina, US, is the mother of Sadie Rae, who suffers from childhood dementia. Sadie Rae was diagnosed with Sanfilippo syndrome after undergoing multiple brain surgeries, including a shunt in her brain.
The Story of Sadie Rae: A 7-year-old childhood dementia (Sanfilippo syndrome) fighter who is starting to forget how to talk.
Sadie Rae was born in March 2016. Due to respiratory distress syndrome, she had a breathing issue and was airlifted to Levine Children's Hospital in Charlotte. She was put on a ventilator.
Sadie developed a grade III intraventricular hemorrhage.
The first 72 days of Sadie's life were spent in the hospital, undergoing numerous tests and several surgeries, including having a brain shunt placed. Later, she tested positive for Sanfilippo syndrome.
By the age of two, she was saying ABC, counting to ten, and even spelling her name, but at three, her speech began to get affected. She has also forgotten how to eat. Her parents have to remind her to swallow.
Sadie's distant relative happens to be dealing with the same condition.
At the age of three, she was enrolled in one clinical trial, which improved her health, but the trial ended in April 2021, shattering all hopes.
Her mother is now sharing the journey to raise awareness for other parents and raise funds for further research on cures.
In one of her latest posts, she said that recently, the Sanfilippo community has been dealing with the temporary or permanent loss of numerous clinical trials, including Sadie’s treatment.
Sadie's family hopes to find a cure and hopes that this disease never steals Sadie's joy.
Sanfilippo is named after Dr. Sylvester Sanfilippo, a Minnesota pediatrician and researcher. He first described the enzyme defect that causes the disorder.
Children with Sanfilippo syndrome are born with a single genetic defect that causes their bodies to lack an enzyme. This lack of an enzyme makes their bodies unable to break down heparan sulfate (HS), which causes a series of ill effects and death.
Sanfilippo syndrome is also known as mucopolysaccharidosis type III (MPS III) and is classified as a lysosomal storage disorder (LSD).
Children with MPS III begin to show signs and symptoms in early childhood.
Early signs and symptoms are:
Developmental delay or delayed speech
Frequent ear and throat infections
Behavioral problems (restless, hyperactive, destructive, anxious, impulsive, fearless, or aggressive)
May display features of autism spectrum disorder.
An increased tendency to chew on objects or put things in their mouth.
Sleep disturbances
Coarse hair
Excess hair growth (hirsutism)
Slightly coarse facial features
In the later stages of the disorder, children with MPS III may develop seizures, loss of mobility, and movement disorders.
Mutations in the GNS, HGSNAT, NAGLU, and SGSH genes cause MPS III. Currently, there is no FDA-approved treatment or cure. (4)
As per the literature review conducted by Dr. Kristina Elvidge, Head of Research at the Childhood Dementia Initiative, et al., published in the international medical journal Brain (vol. 146, July 20, 2023), the mean age of onset of the disease is 2.5 years, and the age of diagnosis is 4 years.
A diagnosis is found through biochemical testing or genetic testing.
The limited awareness of childhood dementia, even among healthcare providers, can leave the child undiagnosed for many years.
Childhood dementia is believed to have an average age of onset of around two years. Many children with the condition do not begin available treatments and interventions on time, as the diagnosis is often delayed or missed. (4)
Early diagnosis plays an important role in delivering quality care and timely therapeutic intervention for children with dementia. Before the onset of irreversible neuropathology, an early diagnosis gives better chances of successful treatment. (5)
Treatment for 145 disorders is only symptoms management, as there is a scarcity of effective and available treatments. Currently, many clinical trials for childhood dementia are limited to early-symptomatic children.
The average age of diagnosis of Sanfilippo syndrome type A (MPS IIIA) is 4 years, but recruitment for gene therapy clinical trials was limited to those under 2 years of age (NCT02716246, NCT04201405). (6)
Multiple-gene therapies have shown promising results for childhood dementia treatment. Currently, 28 clinical trials of gene therapies for childhood dementia disorders are active (from June 2021, clinicaltrials.gov).
Two gene therapies have received regulatory authorization. Skysona (Bluebird Bio) for cerebral X-ALD (approved in the USA and EU) and Libmeldy (Orchard Therapeutics) for metachromatic leukodystrophy (approved in the EU). (2)
References:
1. Nunn K, Williams K, Ouvrier R. The Australian Childhood Dementia Study. Eur Child Adolesc Psychiatry. 2002 Apr;11(2):63-70. doi: 10.1007/s007870200012. PMID: 12033746.
2. Kristina L Elvidge, John Christodoulou, Michelle A Farrar, Dominic Tilden, Megan Maack, Madeline Valeri, Magda Ellis, Nicholas J C Smith, the Childhood Dementia Working Group, The collective burden of childhood dementia: a scoping review, Brain, Volume 146, Issue 11, November 2023, Pages 4446–4455, https://doi.org/10.1093/brain/awad242
3.Childhood Dementia Initiative. Childhood dementia in Australia: quantifying the burden on patients, carers, the healthcare system and our society. https://www.childhooddementia.org/burdenstudy. Accessed April 4, 2022; 2020.
4. Source: Cure Sanfilippo Foundation, Columbia
5. Sevin C, Deiva K. Clinical Trials for Gene Therapy in Lysosomal Diseases With CNS Involvement. Front Mol Biosci. 2021 Sep 16; 8:624988. doi: 10.3389/fmolb.2021.624988. PMID: 34604300; PMCID: PMC8481654.
6. Chin SJ, Fuller M. Prevalence of lysosomal storage disorders in Australia from 2009 to 2020. Lancet Reg Health West Pac. 2021 Dec 12;19:100344. doi: 10.1016/j.lanwpc.2021.100344. PMID: 35024668; PMCID: PMC8671750.
