Analysis of the caregiver burden associated with Sanfilippo syndrome type B: panel recommendations based on qualitative and quantitative data

Caregiver burden remains high throughout the life of the affected child but changes as symptoms progress (Fig. 1a). The average time from the appearance of initial symptoms to a confirmed diagnosis was 3 years (range, 1–9 years), with an average age at diagnosis of 4.8 years (range, 1.5–12 years). The major sources of impact on caregiver burden were the emotional impact of coping with the disease on a daily basis, associated behavioral factors (especially ‘aggressiveness’, hyperactivity, impulsiveness, and sleep disturbances), and communication difficulties with the child. Clinicians recognized physical symptoms such as loss of mobility and sleep disturbances in patients about 7 and 2 years earlier, respectively, than parents. Behavioral symptoms such as ‘aggressiveness’, hyperactivity, and lack of fear were recognized by clinicians about 1 to 2 years earlier than parents. In contrast, parents recognized the onset of speech deficits in their child before clinicians (Fig. 1b). Other important sources of caregiver burden were impact on the ability to work and financial stability, physical demands of providing care, QoL of caregivers, and impact on the family.

The psychological stress and physical exhaustion experienced by parents due to the continual caregiver burden leads to feelings of isolation and depression that are reinforced by the child’s progressive loss of acquired skills as the disease progresses.

The disease progression and burden timelines identified during the secondary research were more protracted compared with the panel’s experience. In the panel’s experience, diagnosis of Sanfilippo B is rarely made at infancy rather characteristic clinical features are generally recognized between age 1 and 8 years, hyperactivity peaks at 3.5 to 4 years, and key skills tend to stop developing at an earlier age (ie, from 3 years onward).

An early diagnosis can help reduce the initial caregiver burden; however, the rarity of the disease and associated subtle phenotypes mean that patients often encounter multiple physicians before being diagnosed. Overlooked screening triggers identified by the panel that should be recognized in correctly diagnosing Sanfilippo B include a slowing in and halting of development; the loss of acquired skills; and physical symptoms including subtle features of dysmorphia (including macrocephaly), joint stiffness, and hirsutism (especially in eyebrows). In addition, tests such as enzymatic testing, urine tests for glycosaminoglycans, and genetic testing are also important in enabling a correct diagnosis.

A broader awareness of Sanfilippo B within the global medical community is needed to lessen the major sources of caregiver burden, particularly with regard to the behavioral and functional symptoms of Sanfilippo B. Age and disease stage of the patient, in particular, determine the severity and impact on QoL of caregivers and the family. 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. Importantly, the lack of intentionality of the child’s behavior is recognized and shared by parents and panel members. Parents may seek to protect their child from public scrutiny and avoid situations that many engender criticism of their parenting skills.

Overall, the panel agreed that the following are important in lessening the burden of behavioral and functional symptoms on caregivers: ability of the child to communicate broadly and functionally with parents, clearly defined criteria for measuring treatment effects, and availability of treatment.

The daily responsibilities of the caregiver leave little time to focus on anything else (Table 2). The impact of Sanfilippo B on the overall QoL of caregivers is influenced by emotional, social, and professional elements. The emotional impact on caregivers is driven by psychological stressors (eg, anxiety, depression) and cumulative physical exhaustion associated with caring for the patient. Families are often restricted in doing normal activities, which leads to feelings of social isolation. Career development and professional aspirations are often halted or limited, and financial concerns may become an issue. The level of impact on the QoL of the child and family will differ depending on the age, symptoms, and behavior of the patient (Fig. 2).

There is a continuum of symptoms and behaviors that have a cumulative impact on caregiver burden and the QoL of families. The changing care needs of the patient lead to a “stress cycle” associated with the emergence and evolution of symptoms and associated needs of the patient as the disease progresses (Fig. 3).

Caregiver burden can fluctuate depending on day-to-day circumstances, such as poor sleeping patterns or stressful environments that exacerbate behaviors. For example, recognition of sleep disturbances may be due to differences in definition and may be noted by parents before clinicians. Because the child’s sleeping pattern cannot be broken, parents may normalize this behavior and often sleep with their child, as this may lead to decreased stress.

Neurologic abnormalities present additional challenges such as mood problems (eg, episodes of distress triggered by specific incidents), but these are often time-limited, differ by the phase of the disease, and may be viewed as more intense at onset by siblings and other relatives. Communication between the parent and child can also be challenging. Although other forms of communication beyond speech are available, parents may not be aware of these services or be able to justify the child’s need for such interventions to therapists or insurance providers.

Disease progression can be rapid, and parent expectations can change; thus, physicians must provide realistic expectations regarding the impact on the patient and family. In general, caregiver burden shifts over time from managing behavioral issues to the provision of physical and medical care as the skills acquired by the child are lost. The impact this has on families is often overlooked and may be displayed via compensatory coping mechanisms (eg, carrying the child or limiting social engagements). Siblings may receive less attention from their parents, resulting in less communication with parents and a feeling of social isolation. The long-term effects on siblings is unclear. Overall, the panel agreed that given the burden placed on caregivers and families, early counseling, mental health screening of parents and family members, and a support network are vital.

A number of supportive measures could be put in place to mitigate caregiver burden (Table 3). The panel agreed that many of these supportive measures should be introduced early to set realistic expectations and minimize the emotional and physical burden associated with the disorder.

Although generic caregiver and patient questionnaires have been used to assess various forms of mucopolysaccharidosis [9, 19‐21], a Sanfilippo-specific QoL questionnaire is needed to help better align caregiver and clinician assessments of caregiver burden. This could be a generic Sanfilippo-specific QoL questionnaire as Sanfilippo B differs little from type A. Specific QoL questionnaires have been developed for other degenerative neurologic disorders in adults such as Alzheimer disease [22, 23] and Huntington disease [24, 25]. Additionally, the direct and indirect economic impact of conditions such as Dravet syndrome [26] or tuberous sclerosis [27] may be useful in guiding the development of a Sanfilippo-specific QoL question, given that these conditions are associated with similar issues (eg, multiple comorbidities, reduced QoL for patient and caregiver, reduced work productivity for caregiver). The questionnaire would allow clinicians to better understand the effects on caregivers in terms of their emotional, physical, mental, and social well-being and the impact that care has on the financial status of the caregiver. Development of a questionnaire presents an opportunity to properly define the aspects of the disease that most affect QoL. A phase-dependent series of questions broken down by age and phenotype is desirable. Furthermore, qualitative and quantitative measurements could be ascribed to particular symptoms or behaviors, such that patient symptoms and response to treatment can be assessed. Although capturing normative data and validation would be challenging, information obtained from such a questionnaire would help guide treatment decisions as the disease progresses.

Clinicians should develop good relationships with the families of Sanfilippo B patients through direct, regular personal contact. Such interaction should include counseling and a full explanation of the patient’s journey at initial diagnosis; management of caregiver expectations regarding diagnosis, symptoms, caregiver burden, and disease progression; and early introduction of quality palliative and respite care. Although management of patients with Sanfilippo B varies by country, the development of an interdisciplinary clinical network that promotes integration of care should be the standard of care. The clinical network can assist in streamlining hospital visits and laboratory investigations, promoting early engagement with support organizations to assist families, and actively monitoring QoL of patients and caregivers, with the ability to initiate referrals for depression screenings where appropriate. Ultimately, treatment guidelines are needed.

Curative treatment is the preferred solution; however, this is not currently a viable option. Although there are a number of different treatments currently under development, the panel believes that treatments that slow disease progression are equally as valuable as treatments that maintain function. As with other progressive neurologic diseases for which no curative treatment is currently available, treatment goals for Sanfilippo B should be focused on the following 3 areas: (1) slowing disease progression and cognitive decline, as reversal of symptoms are not expected, (2) improving the QoL for patients and caregivers, and (3) treating physical and behavioral symptoms. Palliative support is vital, regardless of whether treatment halts disease progression.