Quality of life in hereditary haemochromatosis: Scoping review of symptoms and initial ranking of symptoms by a special interest group

Table 1 Characteristics of included studies

Ref.	Study design	Year published	Country	Sample size	Duration of follow up	QoL tool/or other measure
Acevedo et al[16]	Longitudinal	2022	Brazil	65	About 3 years	SF-36
Adams et al[17]	Cross-sectional	1996	Canada	50	NA	MOS-SF36
Adams et al[18]	Longitudinal	2021	Canada	527 C282Y homozygotes and 12879 controls	Median 17.7 years	Linked health administrative database
de Graaff et al[19]	Cross-sectional	2016	Australia	221	NA	AQOL-4D, HSUV
Meiser et al[20]	Longitudinal	2005	Australia	101	12 months	SF-36 (mental health component scores)
Hicken et al[21]	Cross-sectional	2004	United States	118 younger adults, 50 older adults	NA	Self-reported attitudes towards genetic testing
Hicken et al[22]	Cross-sectional	2004	United States	87 patients, 50 controls	NA	Structured interviews and self-reported psychosocial outcomes
Adams et al[23]	Decision analysis	1995	Canada	170 hemochromatosis homozygotes	NA	NA
Gallego et al[24]	Longitudinal	2015	United States	98 homozygotes, 397 compound heterozygotes	NA	NA
Sherrington et al[25]	Population-based study	2006	Australia	1372 hereditary haemochromatosis patients	NA	Questionnaire and physical examination
Ryan et al[26]	Observational study	2002	Ireland	109 (79 C282Y homozygotes, 30 hereditary haemochromatosis probands)	Not provided	Not specified
Ellervik et al[27]	Meta-analysis	2007	Denmark	202 studies, 66263 cases, 226515 controls	NA	Not specified
Sahinbegovic et al[28]	Cross-sectional observational study	2010	Germany	199 hereditary haemochromatosis patients	Not provided	Not specified
Beutler et al[29]	Cross-sectional observational study	2002	United States	41038 individuals	Not provided	Not specified
Allen et al[30]	Cohort study	2008	Australia	31192 participants	12 years	Not specified
Pilling et al[1]	Cohort study	2019	United Kingdom	451243 participants	7 years	Not specified
McCune et al[31]	Observational study	2006	South Wales	239 first-degree relatives of 116 index cases	Not provided	SF-36 version 2
McDonnell et al[32]	Cross-sectional study	1999	United States	2851 respondents	Not provided	Not specified
McNeil et al[33]	Observational study	1983	United States	10 hereditary haemochromatosis patients	Not provided	Not specified
Milman et al[34]	Nationwide survey	2001	Denmark	179 hereditary haemochromatosis patients	Median 8.5 years	Not specified
Shaheen et al[35]	Survey	2003	United States	126 subjects with hereditary haemochromatosis and 46 sibling controls	Not provided	SF-36 and SCL-90-R
Ong et al[36]	Prospective, multicentre, randomised patient-blinded trial	2015	Australia	Not provided	Not specified	MFIS, HADS, SF36v2, AIMS2-SF
Ong et al[37]	Multicentre, participant-blinded, randomised controlled trial	2017	Australia	104	Not specified	MFIS
Adams et al[38]	Retrospective analysis	1991	Canada	93	Not specified	Not specified
Adams et al[39]	Retrospective analysis	1991	Canada	85	Mean 8.1 years (range 0-31)	Not specified
Adams et al[40]	Retrospective analysis	1997	Canada, France	410	Not specified	Not specified
Adams et al[41]	Cross-sectional study	2005	Canada, France	99711	Not specified	Not specified
Fonseca et al[42]	Observational study	2018	Brazil	79	Not specified	SF-36
Brissot et al[15]	Cross-sectional study (online survey)	2011	United States, France, Ireland, United Kingdom	210	Not specified	Not specified
Pilling et al[43]	Cohort study	2022	United Kingdom	2890 (1294 males, 1596 females)	Up to 14 years	Polygenic scores
Moirand et al[44]	Cross-sectional study	1997	France and Canada	352 (176 women, 176 men)	Not specified	Not specified
Rossi et al[45]	Cross-sectional study	2001	Australia	3010 (1488 females, 1522 males)	Not specified	Not specified
Sánchez-Luna et al[46]	Retrospective cohort study	2017	United States	162 (118 C282Y homozygotes, 44 compound heterozygotes)	10 years	Not specified
van der Plas et al[47]	Cross-sectional study	2007	Netherlands	Not provided	Not specified	Liver Disease Symptom Index, Short Form-36, Multidimensional Fatigue Index-20
Smith et al[48]	Cross-sectional survey	2018	International (predominantly United Kingdom)	About 2000	Not specified	Survey (self-reported symptoms and experiences)
Tamosauskaite et al[49]	Cross-sectional study	2019	United Kingdom	200975	Not specified	Not specified
Dallos et al[50]	Cross-sectional study	2010	European Union	170	Not specified	Radiographic scoring system
Wenzel et al[51]	Cohort study	2007	United States and Canada	1478	Approximately 1 week after screening results	Health-related QoL assessments and health worries survey
Adams et al[52]	Cross-sectional study	1992	Canada	57 families	Not specified	Not specified
Altes et al[53]	Cross-sectional study	2007	Spain	100 C282Y homozygous probands	Not specified	Not specified
Bomford et al[6]	Observational study	1976	Canada	85 treated patients, 26 untreated patients	Not specified	Not specified
Cheng et al[54]	Observational study	2009	United States	182 hereditary haemochromatosis patients	Not specified	Not specified
Dar et al[55]	Retrospective review	2009	United Kingdom	22 hereditary haemochromatosis patients post liver transplant	46 months	Not specified
Fargion et al[56]	Retrospective cohort study	1992	Italy	212 patients (181 men, mean age 50 +/- 11 year; 31 women, mean age 49 +/- 10 year)	44 months	Not specified
Hamilton et al[57]	Longitudinal study	1981	Not specified	18 hereditary haemochromatosis patients	10 years	Not specified
Mohammad et al[58]	Cross-sectional study	2013	Ireland	395 patients	1 year	Not specified
Waalen et al[59]	Observational study	2002	United States	41599 subjects screened; 124 filled out questionnaire; 17 completed physician interview	2 years	Not specified

SF 36: 36 item short form health survey; MOS-SF36: Medical outcomes study 36-item short-form health survey; AQoL-4D: Assessment of quality of life-4 dimensions; HSUV: Health state utility value; SCL-90-R: Symptom checklist-90-revised; MFIS: Modified fatigue impact scale; HADS: Hospital anxiety and depression scale; SF-36v2: 36-item short form health survey, version 2; AIMS2-SF: Arthritis impact measurement scales 2- short form; NA: Not available.

Table 2 Frequency of symptoms reported in eligible studies

Symptom	Referenced articles	Frequency of references
Joint pain or stiffness	37	762
Abdominal pain	26	416
Fatigue, chronic fatigue, tiredness	24	314
Problems related to insurance or unemployment	11	111
Reduced psychological wellbeing (depression or low mood)	14	97
Sexual problems (decreased libido or impotence)	21	91
Skin darkening or pigmentation	18	74
Cognitive issues (confusion, memory loss, brain fog)	8	55
Early menopause/issues with menstruation, missing periods or irregular periods/fertility issues	4	25
Hair loss	3	23
Unexplained weight loss	7	22
Reduced physical functioning/ability to do daily tasks	8	20
Heart fluttering or arrhythmia	4	19
Issues with social functioning	6	18
Reduced vitality	6	17
Weakness	6	13
Itchiness	2	10
Breathing problems	3	7
Unexplained weight gain	1	1