Table 1.
Main characteristics of the reviewed studies
| Author, year (origin) | Metabolic disease | N * | Reviewed sample vs. originally reported sample | Mean age in years (range) | Group of comparison | Assessment instrument (report) | Selected results** (IT-IEM related to group of comparison) |
|---|---|---|---|---|---|---|---|
| Beauchamp et al., 2009 (Australia) [25] | GA I | 4 | Same | 5.8 (5 to 7) | Population norms | • CBCL (proxy-mother) | • Psychological adjustment (CBCL): No sign. group difference, except for CBCL total scale, where IT-IEM patients show less behavioural problems than the norm population (doubt about reliability of this result) |
| • ABAS (proxy-mother) | • Adaptive functioning (ABAS): No sign. group difference | ||||||
| Cazzorla et al., 2012 (Italy) [22] | OTCD, HHH Syndrome, ASA, GA I, MMA, MSUD | 15 | Reviewed sample: only IT-IEM Orig. sample: IT-IEM mixed with other diseases (N = 82) | 25.6 (17 to 44) | Population norms, other IEM-groups: PKU, Morbus Fabry, pharmacological treatment | • WHOQOL-100 (self) | • QoL (WHOQOL-100): Compared to population norms: sign. higher QoL for physical domain, lower for environmental domain, no sign. group difference for all other domains |
| • QoL (WHOQOL-100): Compared to other IEM: no sign. group difference compared to PKU for all domains, sign. higher compared to Morbus Fabry and pharmacologically treated patients in most domains (no sign. group difference for social and environmental domains) | |||||||
| Eminoglu et al., 2013 (Turkey) [23] | MA, PA, MSUD (group includes n = 3 patients with a disease not being an IT-IEM) | 14 | Reviewed sample: separately reported subgroup, mainly IT-IEM, 3 other IEM Orig. sample: IT-IEM mixed with other IEM (N = 68) | 4.7 (n.a., SD = 4.3) | Population norms, other IEM-groups: CMD and AMD | • Questionnaire constructed by authors: QoL Scale for Metabolic Diseases (proxy-parent) | • HrQoL (QoL Scale for Metabolic Diseases): Sign. lower compared to CMD and AMD for school status and health perception domains, sign. lower in physical function domain compared to AMD, similar for other domains |
| • Kiddy-, Kid- Kiddo-KINDL (proxy-parent, self if > = 4 years) | • HrQoL (KINDL): No sign. group difference compared to CMD and AMD for emotional wellbeing domain | ||||||
| Gramer et al., 2013 (Germany) [19] | ASLD, GA I, IVA, PA, MSUD | 34 | Reviewed sample: only IT-IEM Orig. sample: IT-IEM mixed with other IEM (N = 187) | 4 (1.2 to 9.7) | None | Questionnaire constructed by authors, assessing: | |
| • Perceived burden for the child (proxy-parent) | • Psychological adjustment (Perceived burden for the child): Rated as low for the majority (50%) | ||||||
| • Social behavior (proxy-parent) | • Psychological adjustment (Social behaviour): Rated average for the majority (82%) | ||||||
| Grünert et al., 2013 (Germany) [26] | PA | 48 | Same | 5 (5 days to 19) | Population norms | • Kid-KINDL (self): n = 18 | • HrQoL (KINDL): Sign. lower HrQoL for psychological and friends domain, sign. higher for school domain, no group difference for other domains |
| • For Kid-Kindl: 11 (5 to 18) | • SDQ (proxy-parent): n = 48 | • Psychological adjustment (SDQ): More problems in all scales except conduct problems | |||||
| • For SDQ: 4 (1 to 18) | n according to age or degree of mental retardation | ||||||
| Krivitzky et al., 2009 (USA) [27] | UCD | 92 | Same | 7.2 (0.4 to 16.75) | Population norms | • ABAS (proxy-parent): all ages | • Adaptive functioning (ABAS): General score was sign. lower for all IT-IEM groups (neonatal onset, late onset, patients with/without hyperammonemic history) in the age group of 3-16 years |
| • Adaptive functioning (ABAS): General score was sign. lower for the IT-IEM patients with a hyperammonemic history, not for the other subgroups, in the age group of < 3 years. | |||||||
| • CBCL (proxy-parent): for ages 3-16 | • Psychological adjustment (CBCL): No sign. group difference in internalising and externalising problems | ||||||
| Mazariegos et al., 2012 (USA) [20] | MSUD | 31 | Reviewed sample: Patients with results for adaptive functioning Orig. sample: Patients with and without results for adaptive functioning (N = 35) | 9.9 (1.7 to 32.1) (for N = 35) | Population norms | • ABAS (self) or Vineland (self) (for this review: only pre-transplantation assessment) | • Adaptive functioning (ABAS or Vineland): Sign. lower score for adaptive functioning |
| • Risk factor assessment: Sign positive correlation between IQ and adaptive functioning | |||||||
| • Risk factor assessment: No sign. correlation between adaptive test scores and age at diagnosis, number of preceding metabolic crises, number of hospitalizations, age at transplantation | |||||||
| Muelly et al., 2013 (USA) [24] | MSUD | 26 | Reviewed sample: IT-IEM patients on diet, not liver-transplanted Orig. sample: IT-IEM patients on diet and IT-IEM after liver transplantation (N = 37) | • For MSUD diet n = 26: n.a., Mdn = 19.5 (7 to 35) | Healthy control group (mostly siblings of MSUD-patients) | • SCID (adult or childhood version) for DSM-IV: depression, anxiety, ADHD, global, social, occupational and psychological functioning (self) | • Psychological adjustment (Severity of depression and Anxiety, BDI, BAI, BYI): No sign. group difference |
| • Psychological adjustment (Current and lifetime depression and anxiety, SCID for DSM-IV): Sign. more lifetime depression and anxiety | |||||||
| • For controls n = 26: n.a., Mdn = 15.9 (6 to 35) | • BDI and BAI or sub-scores of the BYI of emotional and social impairment (self) | • Risk factor assessment: Patients who remained asymptomatic throughout newborn period vs. patients who were encephalopathic at the time of diagnosis: Second group has higher risk to later suffer from anxiety (5x higher) and from depression (10x higher) | |||||
| • Risk factor assessment: Correlation of mood disturbances with some biochemical parameters. No strong correlation of depression and anxiety with indices of lifetime metabolic control | |||||||
| Packman et al., 2007 (USA) [28] | MSUD | 55 | Same | 11 (5 to 18) | Population norms | • PedsQL (self, proxy-parent) | • HrQoL (PedsQL): Total HrQoL score and domains are closer to cancer sample norms than to healthy sample norms |
| • BASC (proxy-parent, proxy-teacher) | • Psychological adjustment and adaptive functioning (BASC): Mostly no sign. group difference. Sign. more problems in some areas, sign. lower scores in adaptive skills (parent- and teacher-rating) | ||||||
| • Self- vs. proxy-rating: HrQoL self-report > proxy-report for physical, emotional, social domain, no difference for school function | |||||||
| • Self- vs. proxy-rating: Behavioural adjustment proxy parent- vs. proxy teacher-report: parent < teacher for internalising problems (somatization, anxiety) | |||||||
| Pohorecka et al., 2012 (Poland)[29] | TYR I | 8 | Same | 11 (6 to 15) | Population norms | • CBCL (proxy-parent) | • Psychological adjustment (CBCL): Sign. more problems in several scales |
| Simons et al., 2006 (Belgium) [21] | OTCD, GA III, MMA | 11 | Reviewed sample: only IT-IEM Orig. sample: IT-IEM mixed with other IEM (N = 53) | n.a. (0-2 to 16) (for N = 53) | Population norms | • CBCL, TRF, YSR (proxy-parent, proxy-teacher, self if child > 11 years old) | • Psychological adjustment (CBCL): No sign. group difference |
| • K-SADS for DSM-IV diagnosis (self) | • Psychological adjustment (K-SADS for DSM-IV): Psychiatric diagnoses in n = 2, but scale was not applied to the whole sample |
*The N reported corresponds to the highest number of participants for which HrQoL/psychological outcome is reported.
**Results are based on the statistic analysis done for this review. A “significant” outcome means that the calculated 95% CI of the effect size does not include the value of zero and is thus significant on a level of p <0.05 (continuous results) or that the χ2−test revealed a significant result on a level of p <0.05 or lower (dichotomous results). The statements refer to IT-IEM patients related to the respective group of comparison.
Abbreviations diseases: AMD (Amino Acid Metabolism Disorders), ASA (Arginosuccinic Aciduria), ASLD (Adenylosuccinate Lyase Deficiency), CMD (Carbohydrate Metabolism Disorders), GA I (Glutaric Aciduria type I), GA III (Glutaric Aciduria type III), HHH Syndrom (Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome), IEM (Inborn Errors of Metabolism), IVA (Isovaleric Aciduria), IT-IEM (Intoxication-type Inbron Errors of Metabolism), MMA (Methylmalonic Aciduria), MSUD (Maple Syrup Urine Disease), OTCD (Ornithintranscarbamylase Deficiency), PA (Propionic Aciduria), TYR I (Tyrosinemia type I), UCD (Urea Cycle Disorder).
Abbreviations assessment instruments: ABAS (Adaptive Behavior Assessment System), BAI (Beck Anxiety Inventory), BASC (Behavior Assessment System for Children), BDI (Beck Depression Inventory), BYI (Beck Youth Inventory), CBCL (Child Behaviour Check List) with YSF (Youth-report form) and TRF (Teacher-report form), DSM-IV (Diagnostic and Statistical Manual of Mental Disorders IV), Kiddy-, Kid-, Kiddo-KINDL (Revised questionnaire to assess health-related quality of life in children and adolescents), K-SADS (Schedule for Affective Disorders and Schizophrenia for School-Age Children), PedsQL (Pediatric Quality of Life Inventory), SDQ (Strengths and Difficulties Questionnaire), SCID (Structured clinical interview for DSM-IV), Vineland (Vineland Adaptive Behavior Scale), WHOQOL-100 (World Health Organisation Quality of Life assessment).