Logan Paci, a teen with Sanfilippo syndrome.
Image source: SWINDALL, ANDREA. “Teen Battling Sanfilippo Syndrome, AKA ‘Childhood Alzheimer’s,” Inside Edition, 16 Nov. 2023, www.insideedition.com/sites/default/files/images/202311/110923_san_filippo_disease_web.jpg.
In the quiet corners of medical research, there exists a complex and often misunderstood condition known as Sanfilippo syndrome. This rare genetic disorder presents profound challenges for both those affected and their families. Understanding Sanfilippo syndrome is not just a matter of medical expertise, but also one of empathy and perseverance.
Overview of Sanfilippo Syndrome
Sanfilippo Syndrome, also referred to as Mucopolysaccharidosis type III or MPS III is a rare, terminal neurodegenerative disease. It results in the loss of acquired skills in children, accompanied by seizures, movement disorders, and considerable pain and distress, resulting in premature death before reaching the second decade of life. Due to its progressive neurological decline and broad impact on various bodily systems, Sanfilippo Syndrome is frequently compared to "childhood Alzheimer's" or "childhood dementia."
Causes and Subtypes of Sanfilippo Syndrome
The human body makes lengthy chains of sugar molecules known as glycosaminoglycans (GAGs), also known as mucopolysaccharides. These molecules serve several vital functions:
Contributing to the construction of cartilage, connective tissue, nerve tissue, and skin.
Facilitating blood clotting.
Participating in cellular communication processes.
The body keeps making GAGs, and when they finish their work, it breaks them down during metabolism.
In Sanfilippo syndrome, a child is born with a problem in one of the genes responsible for producing enzymes necessary to break down a sugar molecule called heparan sulfate. Because of this gene defect, the body cannot properly break down the used heparan sulfate, causing it to accumulate in cells. This buildup prevents the cells from functioning correctly, potentially leading to organ damage and impacting growth, mental development, and behavior.
There are four subtypes of Sanfilippo, also known as Mucopolysaccharidosis type III: Types A, B, C, and D. They can also be labeled as MPS IIIA, MPS IIIB, MPS IIIC, and MPS IIID, or Sanfilippo A, Sanfilippo B, Sanfilippo C, and Sanfilippo D. Each subtype is linked to a specific enzyme that is either deficient or malfunctioning in the body's breakdown of heparan sulfate.
Subtypes
Type A is generally regarded as the most severe subtype of Sanfilippo syndrome. This implies that individuals with Type A typically experience a rapidly progressing form of the condition, resulting in earlier loss of abilities such as speaking and walking, and ultimately, an earlier death.
On average, Type B may exhibit a somewhat slower progression.
Types C and D of Sanfilippo syndrome typically display more variable rates of progression compared to Types A and B. However, individuals with Types C and D often retain their skills for a longer period compared to those with Types A and B.
Symptoms, Signs, and Progression
Children with Sanfilippo Syndrome usually seem healthy when they are born, and they usually don't show signs of the disease right away. However, some common childhood issues, like developmental delays or behavior problems, might show up early in kids with Sanfilippo. These signs might be easy to ignore, and families might be told that the child will eventually outgrow them.
Early Symptoms:
Fast Breathing After Birth: Some babies breathe quickly right after they're born.
Distinctive Facial Features: Some kids have noticeable features like a big forehead, full lips and nose, and thick eyebrows.
Excessive Body Hair: Some children have more body hair than usual.
Large Head Size: Some kids have heads that are bigger than usual.
Delays in Speech & Learning: Some children might take longer to start talking or learning new things.
Hearing Problems: Some kids might have trouble hearing certain sounds, especially high-pitched ones.
Frequent Ear and Sinus Infections: Some children get a lot of infections in their ears or sinuses.
Persistent Nasal Congestion: Some kids always seem to have stuffy noses.
Difficult Behaviors: Some children might be very active, impulsive, or have trouble behaving well.
Signs Like Autism: Some kids might show signs similar to autism, like losing speech skills, repeating actions, or not being interested in social activities.
Sleep Problems: Some children might have trouble falling asleep, wake up often during the night, or have trouble getting back to sleep.
Digestive Issues: Some kids might have diarrhea or loose stools often.
Belly Button or Groin Hernias: Some children might have hernias in their belly button or groin area.
Larger-Than-Usual Liver or Spleen: Some kids might have bigger-than-normal liver or spleen.
Facial Characteristics in Sanfilippo
Kids with Sanfilippo Syndrome often have certain facial traits. These features tend to become more pronounced as the child gets older.
Prominent Forehead: A forehead that sticks out more than usual, sometimes with a heavier brow ridge.
Thick Eyebrows: Eyebrows that are bigger and have more hair than usual. As the child gets older, the eyebrows become even thicker and might come together.
Full Lips & Nose: Usually, the upper lip is narrow, and the lower lip is very full. The nose tends to be larger than average.
Later Features:
Increasing Coarseness of Facial Features
Emergence of Autism-like Traits
Gradual Decline in Intellectual Abilities
Reduction in Brain Size (brain tissue shrinkage due to nerve cell loss)
Episodes of Seizures or Movement Issues
Behavioral Challenges
Excessive Activity and Impulsiveness
Loss of Ability to Walk
Difficulty with Chewing and Swallowing
Enlarged Liver or Spleen
Hearing Difficulties (often trouble hearing high-frequency sounds)
Premature Passing
Progression
As Sanfilippo advances, children often experience intense hyperactivity and behavioral issues. Sleep disturbances can become severe, with some children staying awake for days or only sleeping a few hours each night. Over time, they progressively lose all the skills they once had, including speaking, walking, and the ability to eat orally.
Image source: Cure Sanfilippo Foundation. “Sanfilippo-Child-Progression-Chart,” Curesanfilippofoundation.org, 2019, curesanfilippofoundation.org/wp-content/uploads/2021/06/Sanfilippo-Child-Progression-Chart-2019-version.jpg.
Photo Array Source: Escolar C, Bradshaw J, Byers V, et. al, 2020, Development of a Clinical Algorithm for the Early Diagnosis of Mucopolysaccharidosis III. Journal of Inborn Errors of Metabolism & Screening. 2020, Volume 8: e20200002.
Diagnosis, Tests, and Treatment
Obtaining a proper diagnosis of Sanfilippo Syndrome can be a lengthy process, often spanning several years because of its rarity and many doctors are not familiar with it, a child's symptoms are often initially attributed to developmental delays or autism. It typically requires a comprehensive medical evaluation to uncover the true underlying cause.
Tests
Typically, the first screening test to detect Sanfilippo syndrome is the Urine MPS Screening (glycosaminoglycans) Analysis. This test identifies whether there is an abnormal level of heparan sulfate in a child's urine.
Another test is a genetic panel test that can be conducted by collecting samples of blood, a cheek swab, or saliva to examine the genes associated with Sanfilippo syndrome.
If there are still concerns following a negative urine test or if either the Urine MPS Test or Gene Panel Test has positive results, confirming the diagnosis should involve a blood enzyme panel.
A blood enzyme assay is deemed the most reliable diagnostic method for Sanfilippo Syndrome as it determines the presence or absence of specific enzymes involved in the cellular breakdown of heparan sulfate (the underlying cause of Sanfilippo Syndrome), offering a definitive diagnosis.
Treatment
Currently, there is no cure for Sanfilippo syndrome. Treatment primarily aims to alleviate symptoms and enhance the child's quality of life for as long as feasible.
Nevertheless, clinical trials for treatments, like enzyme replacement therapy and gene therapy, are underway, while other potential treatments are still in pre-clinical research stages, awaiting funding.
Image Source: any baby can. “Simon Banner,” Anybabycan.org, 13 May 2019, anybabycan.org/wp-content/uploads/2020/04/Simon-banner.jpg.
In conclusion, Sanfilippo syndrome presents numerous challenges for affected individuals and their families. From its elusive diagnosis to the absence of a cure, navigating the complexities of this condition can be daunting.
Ensuring these children have access to the highest possible quality of life, filled with love, support, and opportunities for joy, is important. While treatments like enzyme replacement therapy and gene therapy offer hope for the future, the present demands a focus on providing comprehensive care that addresses the unique needs of each child.
Every moment counts, and every child deserves to experience the fullest life possible, regardless of the challenges they face.
Citations:
“What Is Sanfilippo Syndrome | Cure Sanfilippo Foundation.” Cure Sanfilippo Foundation | Accelerating Discovery of a Cure for Sanfilippo Syndrome, 15 June 2023, curesanfilippofoundation.org/what-is-sanfilippo/#:~:text=Sanfilippo%20Syndrome%20%E2%80%94%20also%20known%20as.
“Sanfilippo Syndrome (for Parents) - Nemours KidsHealth.” Kidshealth.org, Sept. 2019, kidshealth.org/en/parents/sanfilippo-syndrome.html.
“The Early and Later Symptoms of Sanfilippo Syndrome.” Cure Sanfilippo Foundation | Accelerating Discovery of a Cure for Sanfilippo Syndrome, 23 May 2022, curesanfilippofoundation.org/what-is-sanfilippo/what-are-the-symptoms/.
“Testing for Sanfilippo (MPS III) | Cure Sanfilippo Foundation.” Cure Sanfilippo Foundation | Accelerating Discovery of a Cure for Sanfilippo Syndrome, 30 Apr. 2024, curesanfilippofoundation.org/what-is-sanfilippo/if-you-suspect-sanfilippo/testing-for-sanfilippo/.
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