Table 2 Summary of design and parameters measured in natural history studies in MPS III
From: Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III
Reference | Geographical region(s) | Subtype(s) (n) | Design | Parameters measured |
|---|---|---|---|---|
Meyer et al. (2007) [29] | Germany | MPS IIIA (71) MPS IIIB (14) MPS IIIC (4) | Retrospectively collected data based on family interviews using a questionnaire and FPSS | Questionnaire: Family history, onset of symptoms, diagnostic tests, physical symptoms, developmental delay, behavioural problems, sleep disturbance, neurological symptoms, physical development/puberty, therapies and medications, social care, developmental regression, death FPSS: motor function, speech abilities, cognitive function; assessed retrospectively over course of disease at 3–6 month intervals |
Ruijter et al. (2008) [28] | Netherlands | MPS IIIC (29) | Retrospectively collected data based on paediatrician and geneticist interview with family using a questionnaire, or case note review for deceased patients | Questionnaire: pregnancy, first clinical signs and symptoms, mental and motor milestones, behavioural and sleep problems, medical history DNA sequencing HGSNAT activity in fibroblasts |
Malm et al. (2010) [2] | Sweden | MPS IIIA (15) MPS IIIB (1) MPS IIIC (5) | Retrospective case notes review with completion of missing data by interview with families | Motor function and loss of ability, speech development and loss of ability, mental development using IQ measures from locally applied neuropsychological tests (not specified), clinical symptoms and somatic features including behavioural problems, sleep, epilepsy, umbilical or inguinal hernia, orthopaedic problems Enzyme assay in leukocytes or fibroblasts |
Valstar et al. (2010) [64] | Netherlands | MPS IIIB (52) (majority with attenuated phenotype) | Retrospectively collected data based on clinician interview with family using a questionnaire, or case note review for deceased patients | Questionnaire: pregnancy and delivery, first clinical signs and symptoms, mental and motor milestones, behavioural problems, sleeping problems, medical history Clinical examination DNA sequencing |
Valstar et al. (2010) [30] | Netherlands | MPS IIIA (110) | Retrospectively collected data based on clinician interview with family using a questionnaire, or case note review for deceased patients | Questionnaire: pregnancy, first clinical signs and symptoms, mental and motor milestones, behavioural problems, sleeping problems, medical history FPSS as used in Meyer et al. (2007) Clinical examination DNA sequencing |
Heron et al. (2011) [5] | France, UK, Greece | France - MPS IIIA (76) - MPS IIIB (16) - MPS IIIC (13) - MPS IIID (6) UK - MPS IIIA (89) - MPS IIIB (22) - MPS IIIC (7) - MPS IIID (2) Greece - MPS IIIB (16) - MPS IIIC (3) | France, Greece: retrospectively collected data from participating physicians without direct contact with families using pre-established form UK: retrospectively collected data from telephone interview with families conducted by UK MPS Society using pre-established form | Pre-established form: Presence of specified clinical features at diagnosis and occurrence during follow up, e.g. early language, loss of walking, cognitive delay, abnormal behaviours, school level Enzyme activity in leukocytes or fibroblasts DNA sequencing |
Grant et al. (2013) [81] | UK | Parents (23) of children with MPS III (19) Parents (23) of children with ID (20) | Child behaviour and parental psychological functioning. Questionnaire packs sent out to families and completed at a single time point. | Behaviour: LDCMS, ECBI Parental psychological functioning: Resilience Scale for Adults, Multidimensional Scale of Perceived Social Support, coping techniques (Brief COPE questionnaire), Paediatric Inventory for Parents, parental anxiety and depression (General Health Questionnaire, GHQ-12) |
Delgadillo et al. (2013) [24] | Spain | MPS IIIA (34) MPS IIIB (11) MPS IIIC (10) | Retrospectively collected data using a questionnaire answered by physicians and parents | Questionnaire: early psychomotor development, age at diagnosis, first clinical symptoms, somatic features, speech, behavioural and sleep disturbance, evolution of neurodegenerative symptoms, age at regression of acquired skills and loss of functional abilities, feeding, cognitive failure through the disease, orthopaedic complications, death Details of previously conducted enzyme assays and mutation analysis |
Mahon et al. (2014) [76] | UK | MPS IIIA (4) MPS IIIB (4) | Prospective study over 7Â days of eight children with MPS III and eight age-matched typically developing controls | Actigraphy Salivary melatonin concentrations Sleep questionnaire and daily sleep diary |
Cross et al. 2014 [108] | UK | MPS III (20) ID (24) | Assessment of behaviour and adaptive skills. Questionnaire packs sent out to families and completed at a single time point. | Behaviour: LDCMS, ECBI, Aberrant Behaviour Checklist, SBRS Adaptive skills: VABS-II |
Buhrman et al. (2014) [60] | USA | MPS IIIA (46) | Retrospectively collected data using a standardised protocol of assessments conducted at a single visit by an MDT (neurodevelopmental pediatricians, speech and language pathologists, developmental specialists, psychologists, audiologists, physical therapists) | Age at diagnosis and initial symptoms, Audiology assessments Cognitive function, adaptive behaviour, expressive and receptive language, motor development (neuropsychological instruments not specified) Behavioural symptoms Somatic symptoms Growth parameters (height, weight, BMI, head circumference) Survival |
Mumford et al. (2015) [77] | UK | MPS IIIA (4) MPS IIIB (4) | Prospective study of children with MPS III and age-matched typically developing controls over 7–10 days | Actigraphy |
Shapiro et al. (2016) [58] | USA | MPS IIIA (25) | Longitudinal data collected prospectively over a 2Â year follow up period with evaluations at baseline, 6Â months, 12Â months and 2Â years | Cognitive assessments (KABC-II or BSID-III), reported as age equivalent scores and DQs Adaptive behaviour (VABS-II), age equivalent scores and DQs Disability (FPSS four-point scoring system) Sleep Habits Questionnaire Volumetric MRI of brain (cortical grey matter volume, white matter volume, ventricular volume) Volumetric MRI liver and spleen Total uGAG by DMB assay CSF biomarkers (HS by LC-MS/MS; T-tau, p-tau by immunoassay) |
Truxal et al. (2016) [57] | USA | MPSÂ IIIA (15) MPSÂ IIIB (10) | Longitudinal data collected prospectively over a 1Â year follow up period with evaluations at baseline, 6Â months and 12Â months | Medical history, physical examinations conducted by a physician trained in neurology or genetics Cognitive assessments (Leiter-3 or Leiter-R, reported as age-normed standard scores; later amended to Mullen Scales of Early Learning reported as age equivalent scores) Adaptive behaviour (Achenbach Child Behaviour Checklist, reported as age and gender-normed T-scores; or Adaptive Behaviour System, but removed in favour of VABS-II, reported as age-normed composite standard scores) Pediatric Evaluation of Disability Inventory (PEDI), timed motor function tests (timed 10Â min walk, 6MWT, timed ascent/descent of 4 stairs) MRI volumetric measurements of liver and spleen MR/MR spectroscopy of brain (no longitudinal volumetric studies of brain regions) Echocardiography SGSH or NAGLU enzyme activity in CSF SGSH enzyme activity in leukocytes or NAGLU enzyme activity in plasma uGAG by DMB assay Complete blood count, coagulation studies, liver enzyme tests in blood CSF glucose, protein and cell count Routine urinalysis |