Possible clinical somatic symptoms, although rare, include coarse facial features with broad eyebrows, dark eyelashes, dry and rough hair, and skeletal pathology that affects growth.
However, patients start to become increasingly immobile and unresponsive, as individuals with Sanfilippo syndrome will gradually lose their motor skills, often require wheelchairs, and develop swallowing difficulties and seizures.
[8] The most common symptoms seen in individuals with Sanfilippo syndrome are neurological and may include intellectual disabilities, impaired language development, abnormal movements, and trouble sleeping; however, other symptoms commonly seen are excessive hair growth, chronic ear infections, respiratory infections, and poor nutrient absorption.
[12] Growth velocity decelerates dramatically after the age of 5, and by the time children with Sanfilippo syndrome reach 17, all individuals are significantly shorter than their reference groups.
[13] Type C is considered the least aggressive form of Sanfilippo syndrome, with patients' average life expectancy between 19 and 34 years of age, depending on the study.
People with one working copy are genetic carriers of Sanfilippo syndrome and do not show symptoms, but they may pass down the affected gene to their children.
[5] Symptoms due to Sanfilippo Syndrome arise because the body cannot break down a type of sugar chain called heparan sulfate.
[20] The build up of these sugar molecules can occur in the brain, spinal cord, and connective tissue of various organ systems which are what led to the range of symptoms associated with Sanfilippo syndrome.
HSPGs are key players in various signaling pathways, controls neural progenitor proliferation, and other essential processes within the CNS.
[13] Sanfilippo syndrome types A, B, C, and D are considered to be clinically indistinguishable, although mutations in different genes are responsible for each disease.
[26] Diagnosing individuals with Sanfilippo syndrome can be challenging because of the rarity of the disease and variability of the presentation in early symptoms and an accurate diagnosis may take years.
[27] Moreover, other medical conditions that present with physical symptoms such as juvenile idiopathic arthritis or behavioral issues such as Landau — Kleffner syndrome can be mistaken for the disease and prevent early diagnosis of Sanfilippo.
[22] Once a diagnosis has been made, it is important that children are monitored and seen regularly by their healthcare provider to assess the progression of disease, decline of normal function, and to identify other health issues associated with Sanfilippo syndrome such as cardiac, musculoskeletal, and gastrointestinal problems.
[8] While treatment remains largely supportive, research advancements are being made in the fields of pharmacology, stem cell, and genetics to address the disease.
Staying up to date with vaccines against pneumococcal disease is also recommended due to the increased risk of contracting respiratory infections.
Due to the disease's impact on different organs and systems, healthcare professionals from various fields are involved and integral in managing the child's symptoms.
[8] Pharmacological interventions for the management of symptoms associated with Sanfilippo syndrome vary depending on the affected organ system.
[22] However, medication usage can still be pursued to treat an individual's symptoms instead of managing Sanfilippo syndrome to improve their quality of life.
[22] Gene therapy in particular is under Phase I/II clinical trial in France since October 2011 under the leadership of Paris-based biotechnology company Lysogene.
[33] However, a challenge of this treatment option is that the enzymes being replaced do not have the ability to cross the blood-brain barrier, one of the places sulfate heparan accumulates.
[15] In studies, injection of the enzyme sulfamidase into the brain or cerebrospinal fluid of mice has been shown to reduce symptoms of the Sanfilippo Syndrome.
[41] In severe cases of Sanfilippo syndrome, less than twenty percent of people survive past 20 years of age.
[42] Sanfilippo syndrome varies geographically, with approximately 1 case per 280,000 live births in Northern Ireland,[43] 1 per 66,000 in Australia,[44] and 1 per 50,000 in the Netherlands.
[13] Studies were performed across several countries assessing the mean age of diagnosis for each type of Sanfilippo syndrome.
[4][25][47] The economic burden of Sanfilippo syndrome worldwide has not been studied; however new research shows the disease's impact in monetary and disability-adjusted life year (DALYs) terms in the United States.
[48] Caregivers for children with Sanfilippo syndrome face a unique set of challenges because of the disease's complex nature.
The burden and impact on caregivers' quality of life is poorly defined and best-practice guidance for clinicians is lacking;[10] however, quantitative data revealed that parents of children with Sanfilippo syndrome have reported they would like to see therapies that target both behavioral issues such as lack of communication, hyperactivity, and frustration, as well as physical symptoms such as motor and sleep issues.
Parents also specified their willingness to try experimental treatments, but were disappointed that most clinical trials limited access to younger children with less disease progression.
[49] A best-practice guidance to help clinicians understand the challenges caregivers face was published July 2019 in the Orphanet Journal of Rare Diseases by a group of international clinical advisors with expertise in the care of pediatric patients with Sanfilippo, lysosomal storage disorders, and life as a caregiver to a child with Sanfilippo.
"[10] Additionally, the authors call for changing the narrative associated with Sanfilippo: "The panel agreed that the perceived aggressive behavior of the child may be better described as 'physical impulsiveness' and is often misunderstood by the general public.