Patients with Sanfilippo syndrome type A function below a two-year-old level in terms of communication, daily living skills and socialization, according to a small follow-up study of the later stages of the disorder. Motor skills were slightly more preserved.
The study also revealed that parent burden shifts from behavioral control to physical management and care as disease progresses.
The study, “Observing the advanced disease course in mucopolysaccharidosis, type IIIA; a case series,” was published in Molecular Genetics and Metabolism.
Three stages of developmental delays have been proposed for patients with Sanfilippo syndrome type A: a first stage, between 1 and 4 years of age, characterized by developmental delays and slowing in cognitive development; a second stage, from 3 to 4 years, characterized by behavioral difficulties, sleep impairment and cognitive decline; and a third stage, at a variable age, with feeding and aspiration (breathing) problems, loss of ambulation, and seizures.
Researchers at University of Minnesota previously conducted a natural history study (NCT01047306) in which they characterized the early- and mid-stage disease process. Now, they intended to follow-up these same 24 participants to assess the course of the end of the second, and the third and most advanced disease stage.
Better understanding of later disease stages could improve palliative care and psychological support for families, the scientists believe.
Specifically, patient follow-up was done by telephone starting two years after completion of the natural history study. Of the 24 patients, 19 had rapid progressing (RP) and five slowly progressing (SP) disease.
Two calls were made to each family. The first was an interview exploring their current psychological status as well as patients’ adaptive behavior — assessed with the Vineland Adaptive Behavior Scales II (VABS-II) that evaluates communication, daily living skills, socialization, and motor skills. All had already been assessed during the natural history study.
The second was an interview on medical and treatment history, which included data of current medications, behavioral problems, surgeries, hospitalizations.
Three of the patients with RP disease had died before the study began. Two more one with RP and another with SP disease — died during data collection. The phone interviews only enabled data collection from 11 patients: four SP (one subsequently died) and seven RP patients, age range 8 to 24 years.
Of the remaining patients, the team learned from social media that one developed seizures, one had pneumonia and a tracheostomy, and another was hospitalized for feeding problems.
Of the RP patients, methicillin-resistant Staphylococcus aureus (MRSA) infection was found in two patients, chronic cough in three, swallowing impairment in two, spells of crying out in one, and sleep problems in another. One patient had two episodes of seizures, but no epilepsy diagnosis was made.
Also, two male patients were hyperactive and two were on the antipsychotic medication risperidone. A gastrostomy tube (G-tube) for feeding was needed in two patients, inguinal hernia repair in one, dental work in three, and gabapentin was being prescribed for four patients for pain.
The only male patient of the three with SP disease that were alive and with full data, had hearing loss with later decline in communication ability, increasingly aggressive behavior, short attention span, and sleep disturbances treated with melatonin.
One of the female patients (age 24) required a mobile G-tube, but was able to eat and drink. She was on daily 300 mg of Zavesca (miglustat, by Actelion) — a medication for Gaucher disease but experimental for Sanfilippo syndrome type A — high-dose genistein, and supplements. The other SP female was 17 years old, did not require medication. Neither had further medical complications in two years.
VABS-II data showed that, among RP patients, losses in age equivalent scores ranged from four to eight months per year, with the youngest patient showing an eight month yearly decline. No differences in communication, daily living skills or socialization were evident. Motor skills were the most preserved with the youngest patients remaining at a two-year-old mobility level.
Conversely, SP patients were highly variable. Two females, aged 17 and 21, were notably stable, although the 21-year-old was at a very low level except for motor function. The 17-year-old was the highest functioning patient and had not lost function in three years. In contrast, her 15 year-old SP male sibling showed an eight-month decline in age equivalency over two years.
Overall, the team noted a low incidence of surgeries, epilepsy, new behavior difficulties, and hospitalizations. The reduced number of new behavior problems is in agreement with the literature, the scientists observed.
However, adaptive levels were very low in all RP patients and in all but one SP patient, with children functioning at below a two-year level in all functions, with motor skills slightly more intact, they noted.
“Delineating the prognosis in SP from RP patients can help parents and caretakers prepare for future challenges,” the investigators wrote. They also cautioned that drawing definitive conclusions is hampered by a full dataset of only 11 patients.
The findings also revealed that parent burden was focused on patients’ physical management, but indicated habituation to the stress found in the natural history study during earlier disease stages.