Table 1 Characteristics of included studies reporting prevalence data

KOL Australia [27]

Case series

NR

33

National Referral Laboratory and QLD laboratory Australian Bureau of Statistics

Enzyme assay performed on fibroblasts and/or leukocytes and/or molecular genetic testing

NR

Meikle 1999 Australia [31]

Retrospective case study

Public

16

National Referral Laboratory, Dept. Chemical Pathology, Women's and Children's Hospital (Adelaide) and the Division of Chemical Pathology, Royal Brisbane Hospitals (Brisbane).

Enzymatic analyses.

NR

Nelson 2003 Australia (W) [18]

Epidemiological study

NR

27

Genetic and hospital files: Princess Margaret Hospital for Children & King Edward Memorial Hospital for Women, Perth. Medical files: Disability Services Commission of W. Australia, Perth. Laboratory records: Dept. Chemical Pathology, Women's and Children's Hospital, Adelaide. The Dept. Clinical Biochemistry, Princess Margaret Hospital for Children, Perth. Membership list of the Society for MPS Diseases (W. Australian Parents Support Group). Records of the Birth Defects Registry of W. Australia.

Diagnosis was confirmed by one dimensional electrophoresis of urinary GAG and/or by enzyme assay on leucocytes or fibroblasts.

NR

KOL Brazil [36]

Retrospective case series

NR

9

Diagnoses recorded by MPS Brazil Network from 2004 until 2014

NR

NR

Applegarth 2000 Canada [30]

Case series

NR

28

Diagnoses made at the Biochemical Diseases Laboratory, Children's Hospital, Vancouver. Birth records from the British Columbia Vital Statistics Agency.

Specific enzyme assays.

NR

Lowry 1971 Canada (BC) [40]

NR

NR

16

Multiple sources of ascertainment: discharge diagnoses from all inpatients in the hospitals in BC, children's outpatient's clinics, public health units, residential institutions for the mentally retarded, the physician's notice of birth, private physicians and special treatment centres.

NR

NR

Lowry 1990 Canada (BC) [41]

Case series

Public

34

The Biochemical Diseases Laboratory (BDL) of the Department of Pathology, B.C.'s Children's Hospital, Vancouver and The B.C. Health Surveillance Registry.

NR

NR

Gomez 2012 Colombia (B&C) [39]

Retrospective case series

Public

9

Record histories: Genetics Laboratory The Victoria Hospital, Bogota (Cundinamarca), District Department of Health, El Salvador, of Ubaté (Cundinamarca), Genetics Outpatient Clinic, and patient care area of municipalities (Fúquene, Simijaca Sutatausa, Susa, Carmen de Carupa, Cucunubá, Lenguazaque, Guachetá Tausa, Boyaca. Medical records of the Institute of Human Genetics at the Pontificia Universidad Javeriana, Bogota, and the databases of patient records affiliates to ACOPEL (Colombian Association of Patients with Lysosomsal Disease). Data for live births were obtained from the Dept. National Statistics (DANE).

All clinical assessment was by a specialist in clinical genetics. The diagnosis was confirmed by electrophoresis GAG in urine test determining enzyme levels in leukocytes performed in specialized laboratories or by both techniques widely used in practice clinical diagnosis of mucopolysaccharidosis.

NR

Malm 2008 Denmark [33]

Retrospective case series

NR

30

In Denmark; until 2003: the Kennedy Institute in Glostrup and the Dept. Clinical Genetics at Rigshospitalet, Copenhagen. Today all diagnostics is performed at Rigshospitalet.

Analysis of GAGs in urine (heparan-, dermatan- and keratansulphate) in persons with a clinically suspected MPS. When urinary levels of GAGs are increased, the findings of a low or deficient enzyme level in lymphocytes or fibroblasts confirm the diagnosis of MPS I-MPS VII

NR

Baehner 2005 Germany [32]

Retrospective epidemiological study

NR

15

The identification of affected patients was attained using the following ascertainment sources: 1. Membership list of the German Society for MPS. 2. Patient records from (a) Children's Hospital, University of Mainz (b) Dept. Pediatrics, and University of Hamburg. 3. Laboratory records from (a) University of Gottingen, (b) University of Munster, (c) University of Heidelberg, (d) University of Greifswald, (e) University of Mainz.

In all cases the diagnosis was confirmed by enzyme assay in serum, leukocytes and/or fibroblasts.

NR

POR Japan [35]

NR

NR

20

Japanese MPS Society

The diagnoses have been performed generally based on enzyme analysis.

NR

KOL Malaysia [28]

Retrospective case series

NR

1

Data collected from 4 major hospitals in Malaysia with clinical genetics service (Hospital Kuala Lumpur, Hospital Pulau Pinang, Hospital Universiti Sains Malaysia, University Malaya Medical Centre).

Reduced GALNS enzyme activity in leukocytes

NR

Poorthuis 1999 Netherlands [37]

Case series

NR

26

The records from the laboratories of the clinical genetic centres involved in the post- and prenatal diagnosis of LSD. The main referral laboratories for the diagnosis of LSD, viz. the clinical genetics centres of Leiden, Nijmegen and Rotterdam, contributed 95% of all cases. Additional information was obtained from the other contributing laboratories.

Cases were enzymatically confirmed, but no details were given.

NR

Moammar 2010 Saudi Arabia (EP) [34]

Retrospective case series

NR

25

Main medical centre in Dhahran, Eastern Province of Saudi Arabia. Birth Statistics from Mortality and Morbidity Reports 1983-2008, Epidemiology Services Unit, Preventive Medicine Services Division, Saudi Aramco Medical Services Organization (SAMSO).

Diagnosis of all glycogen and lysosomal storage disorders was confirmed by enzyme activity estimation on cultured skin fibroblasts, liver biopsy, or leukocytes.

PCR of mithochondrial DNA, oligonucleotide probes to evaluate deletions/rearrangements.

Lin 2009 Taiwan [38]

Retrospective case series

Public

21

Data obtained from: (1) Membership list of Taiwan MPS Society (2) Medical records from (a) Mackay Memorial Hospital, Taipei, Taiwan (b) Taipei Veterans General Hospital, Taipei, Taiwan (c) China Medical University Hospital, Taichung, Taiwan (d) Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan (e) Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (f) National Cheng Kung University Hospital, Tainan, Taiwan (g) Buddhist Tzu Chi General Hospital, Hualien, Taiwan (h) Chang Gung Children's Hospital, Taoyuan, Taiwan (i) Tri-Service General Hospital, Taipei, Taiwan (j) National Taiwan University Hospital, Taipei, Taiwan (3) Laboratory records from Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan (4) Records of Taiwan Foundation for Rare Disorders (5) Records of Bureau of Health Promotion, Department of Health, R.O.C. (Taiwan).

The diagnosis of all patients was confirmed by two-dimensional electrophoresis of urinary GAGs and/or enzyme assay in serum, leukocytes and/or fibroblasts.

NR

Al-Jasmi 2010 UAE [25]

Case series

NR

15

Two metabolic referral centres in UAE, Latifa Hospital (Dubai), Tawam Hospital (Abu Dhabi).

Clinical presentation and biochemical analysis.

Direct genomic sequencing of GALNS gene for MPS IVA.

Nelson 1997 UK (NI) [17]

Case series

NR

27

These were hospital consultants' records; records of the screening laboratory for urinary mucopolysaccharides; the diagnostic indices of the Dept. Medical Genetics; The Queens University of Belfast, The Royal Victoria Hospital, Belfast and The Royal Belfast Hospital for Sick Children; and files of the Hospital activity analysis (Nelson 1986).

Urinary GAGs were examined by 2D electrophoresis. In all cases where the patient was alive at the time of the study, the diagnosis was confirmed by he appropriate enzyme assay.

NR

KOL UK [29]

Case series

NR

38

Whole of the UK including devolved nations Wales, Scotland and Northern Ireland. Data provided by KOL.

Diagnosis will have been made by laboratory on urine GAGS and enzyme analysis. Some will also have mutational analysis.

NR