Table 4 HRQoL studies outcomes

Eom and Lee [12]

Paediatric patients with mitochondrial diseases and with the results of a neuropsychological evaluation

Patients’ perspective

Eligible patients within the clinical range (IQ less than 80 and social quotient less than 70)

99 item K-CBCL for children aged 1.5–5 years and 118-item K-CBCL for children and adolescents aged 6–18 years

Scores range from 0 to 100. The higher the score the more severe the disease. The clinical cut off for displaying a significant level of issues is 63

K-CBCL—total behavioural problems: 62.9 (17.1)

K-CBCL—internalizing problems: 61.3 (16.9)

K-CBCL—externalising problems: 57.5 (13.1)

K-CBCL—externalising problems—withdrawn: 70.1 (17.1)

K-CBCL—externalising problems—somatization: 56.9 (12.7)

K-CBCL—externalising problems—anxiety/depression: 61.8 (16.7)

K-CBCL—externalising problems—social problem: 67.8 (9.9)

K-CBCL—externalising problems—thought problem: 58.8 (11.1)

K-CBCL—externalising problems—attention problems: 66.0 (12.9)

K-CBCL—externalising problems—delinquent behaviour: 55.4 (7.9)

K-CBCL—externalising problems—aggressive behaviour: 57.9 (11.8)

K-CBCL—externalising problems—emotional response: 63.3 (16.1)

K-CBCL—externalising problems—sleep problems: 65.7 (15.1)

K-CBCL—externalising problems—other problems: 59.8 (10.4)

Parents’ perspective

A questionnaire that provides a total stress score and a score for 13 subscales across two broad domains: stress related to characteristics of the child (Child Domain) and stress related to characteristics of the parent (Parent Domain)

Scores range from 0 to 100. The higher the score the more severe the disease. The clinical cut off for displaying a significant level of issues is 84

K-PSI—total parenting stress: 88.6 (9.4)

K-PSI—child total stress: 90.1 (16.5)

K-PSI—child stress—distractibility/hyperactivity: 68.1 (30.9)

K-PSI—child stress—adaptability: 78.6 (31.4)

K-PSI—child stress—reinforcement: 82.9 (17.1)

K-PSI—child stress—demandingness: 93.2 (12.8)

K-PSI—child stress—mood: 77.2 (28.1)

K-PSI—child stress—acceptability: 91.4 (21.5)

K-PSI—parent total stress: 84.1 (24.9)

K-PSI—parent stress—competence: 87.8 (15.5)

K-PSI—parent stress—isolation: 74.9 (28.3)

K-PSI—parent stress—attachment: 88.0 (9.5)

K-PSI—parent stress—health: 79.6 (20.5)

K-PSI—parent stress—role restriction: 68.9 (29.8)

K-PSI—parent stress—depression: 69.9 (30.3)

K-PSI—parent stress—spouse: 65.8 (27.7)

Mothers’ perspective

A 21-item measure of depression was used to evaluate the negative emotions experienced by the mothers

Scores range from 0 to 63. The higher the score the more severe the disease. The clinical cut off for displaying a significant level of issues is 11

BDI (maternal depression): 14.6 (9.1)

Subgroup of paediatric patients with mitochondrial diseases and intractable epilepsy

As above

As above

K-CBCL—total behavioural problems: 66.8 (16.8)

K-CBCL—internalizing problems: 61.1 (16.4)

K-CBCL—externalising problems: 62.6 (12.2)

As above

As above

K-PSI—parent stress—total: 93.9 (9.5)

K-PSI—parent stress—child total: 92.6 (10.6)

K-PSI—parent stress—parent total: 90.1 (14.4)

As above

As above

BDI (maternal depression): 14.7 (9.1)

Hendrix et al. [18]

Patients with mitochondrial diseases

Patients’ perspective

All 17 eligible patients had MERRF

The NMDAS is a measure of disease severity. It is semi-quantitative clinical rating scale designed specifically for all forms of mitochondrial disease

The NMDAS comprises four sections: current function (Section 1), system specific involvement ( Section 2), current clinical assessment ( Section 3), and QoL ( Section 4)

An overall score was calculated for Sections  1–3 (maximum score 145). Section 4 is scored separately and was not reported in this study

Participants were divided in subgroups based on total NMDAS: mild clinical manifestation (≤ 10), moderate disease severity (11 to 20), and severe disease severity (≥ 21)

NMDAS total: 20 (IQR: 12 to 34)

Koene et al. [15]

Patients with Leigh syndrome

Patients’ perspective

Patient 1, 2 and 3 with epilepsy

The NPMDS is a semi-quantitative clinical rating scale designed specifically for all forms of mitochondrial disease

The higher the score the more severe the disease (maximum score of 107 from Sections 1–3; total scores of 0 14 represent mild disease, 15–25 represent moderate disease, and > 25 represent severe disease)

NPMDS Sect. 1: 14 (NR)

NPMDS Sect. 2: 3 (NR)

NPMDS Sect. 3: 15 (NR)

NPMDS total: 32 (NR)

NPMDS Sect. 1: 6 (NR)

NPMDS Sect. 2: 4 (NR)

NPMDS Sect. 3: 9 (NR)

NPMDS total: 19 (NR)

NPMDS Sect. 1: 0 (NR)

NPMDS Sect. 2: 0 (NR)

NPMDS Sect. 3: 6 (NR)

NPMDS total: 6 (NR)

Koga et al. [14]

Patients with a diagnosis of mitochondrial disease involving a known genetic abnormality and a plasma lactate concentration of > 2.5 mmol/L at rest

Patients’ perspective

Of the 3 eligible patients: 1 had cardiomyopathy and 2 had end-stage MELAS

A Japanese version of the NMDAS a semi-quantitative clinical rating scale designed specifically for all forms of mitochondrial disease

The higher the score the more severe the disease (maximum score 80)

JMDRS (CM patient): 65 (NR)

JMDRS (MELAS patient 1): 70 (NR)

JMDRS (MELAS patient 2): 70 (NR)

Patients’ perspective

Of the 3 eligible patients: 1 had cardiomyopathy and 2 had end-stage MELAS

See above

Section 4 assesses QoL using the SF 12v2

Each question in the NMDAS has a possible score from 0 to 5. The higher the score the more severe the disease (maximum score 145)

NMDAS (CM patient): 108 (NR)

NMDAS (MELAS patient 1): 134 (NR)

NMDAS (MELAS patient 2): 141 (NR)

Li et al. [16]

Patients with primary mitochondrial disorders

Patients’ perspective

Both eligible patients had MERRF

The IPMDS was used to assess the severity and natural history of patients with PMDs on the day after admission

Higher scores indicate worse conditions (Koene et al., 2016)

The total score is expressed as a percentage of items which were feasible to perform; therefore, the possible maximum score changes accordingly and can vary between patients [25]

IPMDS domain 1 raw score (MERRF patient 1): 9/103 (8.74%) (NR)

IPMDS domain 2 raw score (MERRF patient 1): 4/61 (6.56%) (NR)

IPMDS domain 3 raw score (MERRF patient 1): 28/44 (63.64%) (NR)

IPMDS total score (MERRF patient 1): 41/208 (19.71%) (NR)

IPMDS domain 1 raw score (MERRF patient 2): 29/103 (28.16%) (NR)

IPMDS domain 2 raw score (MERRF patient 2): 14/63 (22.22%) (NR)

IPMDS domain 3 raw score (MERRF patient 2): 8/59 (13.56%) (NR)

IPMDS total score (MERRF patient 2): 51/225 (22.67%) (NR)

van Kempen et al. [17]

Patients with mitochondrial diseases

Patients’ perspective

All 17 eligible patients had MERRF

See above

Section 4 assess QoL using SF12v2 before 2012 and RAND SF-36 after 2012

The cognition tests performed were a Dutch equivalent of the reading test and a symbol test. The comprehension test was not used because of the absence of a Dutch equivalent

Sections 1 to 3 of the NMDAS contain a total of 29 items and were scored from 0 (no involvement) to 5 (severe involvement). Maximum score 145. Scores ranged from 0 to 70 for Section 4. The sum of all four sections resulted in one mean NMDAS score

Participants were divided into subgroups based on total NMDAS: mild (0–10), moderate (11–20), and severe (> 20)

Mild NMDAS score: 3 out of 15 patients (20%) (NR)

Moderate NMDAS score: 5 out of 15 patients (33.3%) (NR)

Severe NMDAS score: 7 out of 15 patients (46.7%) (NR)

Mean NMDAS score for all 15 patients: 22 (NR)

Wang et al. [13]

Patients with Leigh/Leigh-like syndrome and HIBCH mutations

Patients’ perspective

Of the 3 eligible patients: 1 had DD and 2 had encephalopathy

The NPMDS is a semi-quantitative clinical rating scale designed specifically for all forms of mitochondrial disease

The higher the score the more severe the disease (maximum score 107 from Sections 1–3; total scores of 0–14 represent mild disease, 15–25 represent moderate disease, and > 25 represent severe disease)

NPMDS (DD patient) at peak phase: 36.2 (NR)

NPMDS (DD patient) at last assessment: 53.1 (NR)

NPMDS (encephalopathy patient 1) at peak disease phase (before medication): 48.8 (NR)

NPMDS (encephalopathy patient 1) at last assessment (after medication): 38.7 (NR)

NPMDS (encephalopathy patient 2) at peak disease phase (before medication): 44.8 (NR)

NPMDS (encephalopathy patient 2) at last assessment (after medication): 48.4 (NR)