Table 1 Qualitative and quantitative articles included in this review

Hoffmann et al. [58]

2021

Germany

Cross-sectional

To offer parents specific effective day-today coping measures:

In cooperation with the German MPS Society, a convenience sample of all registered families of children with MPS I, -II & -III & neurological involvement (n = 268) were invited to participate by mail in the summer of 2017

N = 37 (4 males & 33 females)

children were male in 52.9% (n = 18)

M = 8.7 (SD = 4.23) years of age

MPS I, -II or -III

Semi-structured questionnaires. Impact on interfamilial relationships used two-sided VAS-scales (range − 2.50 to + 2.50). Advice for ‘recently diagnosed’ families was collected through free text investigation

Yazdani et al. [47]

2022

Canada

Cross-sectional

To explore the extent to which parents think modifications of healthcare services have affected their families

Parents were identified through the Leukodystrophies &

Neurometabolic Disorders Clinic at the Montreal Children’s

Hospital of the McGill University Health Centre. Sampling was purposeful, & not r&om. Eligible parents were contacted until data saturation was reached

N = 13 (4 males & 9 females)

36–54 years

3–23 years

Genetically Determined Leukoencephalopathies

Semi-structured interviews & sociodemographic form

Eichler et al. [50]

2016

USA

Cross-sectional

To identify relevant clinical/quality-of-life outcomes for patients/parents

Participants were identified via patient support groups: in the United States, France, Germany & Colombia

N = 23 (14 males & 9 females)

Metachromatic leukodystrophies

Semi-structured qualitative interviews & 1 focus group

Needham et al. [55]

2014

USA

Cross-sectional

To describe a population of patients with MPS II in the domain of adaptive functioning, & to examine the impact of MPS II on family functioning & relationships

Patients were recruited through national MPS societies in English-speaking countries, the hunterpatients.com website, the MPSforum.com website, & through contacting geneticists in the United States

N = 73

not reported

12.52 years (SD = 8.88). all patients were male

MPS II (Hunter syndrome)

Questionnaire including stadardised measures (Vinel&-II & PedsQL Family Impact Module) & purpose designed measures (demographics % supplementary Qs for qualitative analysis)

Krantz et al. [51]

2021

Sweden

Cross-sectional

To investigate parents' experience of having a child with CLN3 & how these experiences can be related to family resilience

Parents of children diagnosed with CLN3 disease attending or who had attended Queen Silvia's Hospital in Gothenburg, Sweden were contacted by the research team in February/March 2021

N = 8 (3 males aged 40–51 years & 5 females aged 41–51)

11–24 years, (N = 5 & one patient deceased)

CLN3 disease

Semi-structured interviews

Porter et al. [52]

2021

USA

Cross-sectional

To explore parent-reported impact of Sanfilippo syndrome symptoms on the patient & family, which symptoms were most important to be addressed by future treatments, & what degree of treatment benefit would be considered meaningful

Cure Sanfilippo Foundation recruited participants using email & social media, through the ConnectMPS Registry communication, & by snowball recruitment through existing formal informal parent support networks

N = 25 (6 males & 19 females)

29 to 65 years, with a median age of 38 years

4–36 years with a median age of 8yrs

MPSIII subtype A (17), subtype B (6), or subtype C (2)

Focus groups (× 3) & a questionnaire

Grant et al. [56]

2013

UK

Cross-sectional

To examine the psychological impact of parenting a child with MPS III using valid & reliable measures, with a control group of parents of children with ID, to examine syndrome specific effects of parenting a child with MPS III

Families with a child with MPS III were recruited from the UK MPS Society & the outpatient clinic of Metabolic Medicine at Manchester, as part of a large-scale investigation into the sleep & circadian rhythms of children with MPS III

N = 23 (7 males & 16 females) (& 23 parents of children with ID; 3 M & 20 F)

M = 35.8 (23–49 years)

M = 8.63 (2–15 years)

MPS III

The learning disability casemix scale, ECBI, RSA, MSPSS, Brief COPE, PIP, GHQ-12

Somanadhan et al. [49]

2016

Irel&

Longitudinal

To underst& parents’ experience of living & caring for a child with MPS (1). To examine the knowledge & underst&ing of MPS from the perspective of parents (2). To explore the impact of regular hospitalisation of children living with MPS on family life (3)

Families were recruited from the outpatient clinic of the National Centre for Inherited Metabolic Disorders (NCIMD), Irel& where access to this specialist cohort group was more readily available

N = 8

not collected

6 months-22 years

MPS I Hurler syndrome, MPS II (Hunter syndrome), MPS III (Sanfilippo syndrome)

Interviews

Kuratsubo et al. [60]

2008

Japan

Cross-sectional

To assess mental health in parents of patients with the childhood cerebral form of X-linked adrenoleukodystrophy (CCALD) & to investigate factors relating to psychological problems in order to improve clinical management & quality of life

Mental health examinations & a questionnaire were sent to 40 ALD families who were members of the Japanese

Association of ALD families

N = 37 parents (43% males)

M = 47 years (32–60)

M = 16.8 years (8–24), Years from disease onset 8.7 years (2–16)

X-linked adrenoleukodystrophy (CCALD)

Questionnaire & psychological examinations (BDI-II, GHQ60, STAI)

Varvogli et al. [61]

1999

USA

Cross-sectional

To investigate the psychological profile of mothers whose children carry a mitochondrial disorder

Participants were mothers of children followed by the Mitochondrial Clinic at Children’s Hospital

N = 42

M = 35 (range 23–49 years)

mean age 6 years (N = 50) (range 8 months-22 years)

MELAS, Kearns-Sayre syndrome, PDH deficient, NARP syndrome, Cytochrome oxidase deficiency, Complex I deficiency, Complex III deficiency, Leigh disease, Barth syndrome, Multiple complex deficiency

Phone interview & multiple-choice questionnaire (MMPI-2) to assess personality & psychopathology

Conjin et al.

2018

Netherl&s

Cross-sectional

To assess depression, & parental distress, as well as posttraumatic stress symptoms, in mothers & fathers of MPS III patients compared to Dutch reference groups

Parents of all living MPS III patients under care at the Academic Medical Center (AMC), Amsterdam, were invited by letter to participate in this cross-sectional study

Parents who gave permission to participate received an e-mail with a personal link to online questionnaires

N = 57 (19 males & 26 females)

M = 20, age range 5–38 years

MPS III

scales (HADS, DT-P, SRS-PTSD)

Dermer et al. [57]

2020

Canada

Cross-sectional

To characterize stress experienced by parents of children affected by genetically determined leukoencephalopathies, along with demographic & clinical factors correlating with higher parental stress & demonstrate the feasibility of the Parenting Stress Index–4th Edition

Parents were eligible to complete the questionnaire if their child was between 1 month & 12 years of age. All patients were followed at the Montreal Children’s Hospital of the McGill University Health Center in Montreal, Quebec, Canada. Patients were included if they had a molecular diagnosis of genetically determined leukoencephalopathy or evidence of genetically determined leukoencephalopathy based on the brain MRI pattern

N = 55 (21 males & 34 females)

Between 1 & 12 months old (11%), 1–4 years (33%), 5–7 years (17%), 8–12 years (39%)

Genetically Determined Leukoencephalopathies

PSI-4 (3 domains of parenting stress), Electronic & paper charts were reviewed for each patient & clinical features were recorded & Clinical notes were also used to evaluate the degree of the child’s disability, using validated measures

Ammann-Schnell et al. [62]

2021

Germany

Cross-sectional

To investigate the impact of these diseases on the affected families, e.g. mothers, fathers & non-affected siblings

Families recruited within the nationwide Leukonet natural history study, patient support groups in Germany [ELAGermany, MLD support group “Weisse Wolke” & PCH- Familie e.V.])

N = 43 families, (35 males & 41 females)

11.6

MLD = 30

Semi-structured questionnaire, consisting of a general part & the Pediatric Quality of Life Inventory (PedsQL™) Version 2.0 Family Impact Module (FIM)

Bose et al. [48]

2019

USA

Cross-sectional

To characterize the ZSD caregiver emotional experience in order to develop a comprehensive picture of the specific influences & interactions within a caregiver's daily life

All participants for this study were members of the Global Foundation for Peroxisomal Disorders (GFPD; https://www.thegfpd.org/)., study recruitment fliers were posted on the GFPD website & Facebook page to solicit enrolment. Individuals self-selected to participate

N = 37 (12 males, 25 females)

25–64 years

30 children with ZSD & 7 children with D-bifunctional protein deficiency (DBPD), a clinically-similar peroxisome disorder, participated in the study

Killian et al. [63]

2022

USA

Longitudinal

To characterize relationships between child & caretaker characteristics & caretaker quality of life

N = 727 & N = 220 (30%) had 5 years of follow-up

M = 38 years

M = 9

Rett syndrome

Semi-structured focus group(s)(× 3) & demographic questionnaire

Rozensztrauch et al. [54]

2021

Pol&

Cross-sectional

To underst& the clinical presentation of RTT in relation to QoL & family functioning

Eligible parents were contacted & mailed traditional pencil-&-paper questionnaires together with a stamped, self-addressed envelope in which they were to return the completed survey to the research team. The invitation to participate in the study included a letter & an information packet explaining the study & the questionnaires to complete

N = 23

M = 7 (2–12 years)

Rett syndrome

An author-designed questionnaire (ADQ), the Pediatric Quality of Life Inventory 4.0 generic core scales; PedsQL 4.0), & the PedsQL Family Impact Module (PedsQL-FIM)

Lamb et al. [64]

2016

USA

Cross-sectional

To investigate factors related to family functioning & adaptation in caregivers of individuals with Rett syndrome (RS)

Participants were recruited from 4 clinics across the eastern & south-eastern United States, the 25th Annual Education & Awareness Conference for Rett Syndrome, & various RS organizations & websites. All interested individuals were invited to complete the paper surveys that were mailed to their homes or to visit the online version available on a SurveyMonkey1 platform

N = 396 (90% females)

M = 43, range 22–74 years

M = 13, range 1-50yrs 98% females

Rett syndrome

Quantitative survey (available paper & electronic form) with validated measures of parental self-efficacy, coping methods, family functioning, & adaptation

Palacios-Ceña et al. [27]

2019

Spain

Multi-perspective cohort study

To explore the experiences of a group of caregivers of children with Rett syndrome with regards to living & caring for their children

The researchers explained the purpose & design of the study to the individuals who met the inclusion criteria during an initial face-to-face contact session. A one-week period was then allowed for patients to decide whether or not they wished to participate & they were given a copy of the informed consent for them to review. In a second face-to-face session, they were asked to provide written informed consent & permission to tape the interviews

N = 31; (14 males, 17 females)

M = 45

M = 12 years, range 3–38 years

Rett syndrome

In-depth interviews, focus groups, researchers’ field notes & caregivers’ personal documents

Mori et al. [65]

2019

Australia

Longitudinal

to examine the trajectory of parental well-being among Australian families caring for a child with Rett syndrome over a period of 9 years

Data were sourced from the Australian Rett Syndrome Database (ARSD), housed at the Telethon Kids Institute in Perth, Western Australia.. Data on a comprehensive range of family & child characteristics have been collected via family questionnaires in 1996, 2000, 2002, 2004, 2006, 2009 & 2011, developed in accordance with the specific aims of each wave of data collection in collaboration with a family reference group

N = 198; (92% females)

M = BL: 41 (27-64yrs range) to M = 48 years at end timepoint (30-72trs range)

Rett syndrome

Purpose designed questionnaires including McMaster Family Assessment Device

(FAD) to assess family functioning & parental wellbeing using the short Form 12 Health Survey (SF-12)