Table 2 Studies reporting estimates of birth prevalence of MLD

Europe

Ługowska et al. [41]/retrospective cohort (moderate)

Poland

• Based on diagnosed cases, but diagnostic tests not reported

0.38

• Expected prevalence of conceived fetuses with two pathogenic ARSA variants based on population carrier rates

4.1 (95% CI: 1.8–9.4)

Heim et al. [38]/cross-sectional (moderate)

Germany

• Strongly reduced ASA activity in leukocytes or cultured skin fibroblasts (specific ASA activity level considered to be not specified)

• In the case of multiple sulfatase deficiency, presence of a deficiency of several different sulfatases in fibroblasts or urine

• Clinical characteristics

   – Typical age at onset, development of spastic tetraparesis, incontinence, optic atrophy and peripheral neuropathy in combination with CT- or MRI-proven white matter involvement

0.6

Poupětová et al. [46]/retrospective cohort (moderate)

Czech Republic

• Deficiency of the relevant enzyme

• Presence of the pathogenic variation

• Detection of undegraded substrate by loading tests in cell cultures

All MLD (N = 25): 0.69 (95% CI: 0.29–1.38)

 – Late-infantile (n = 13): 0.31

 – Juvenile (n = 5): 0.11

 – Adult (n = 6): 0.27

Poorthuis et al. [34]/retrospective cohort (good)

Netherlands

• Not specified

All MLD (N = 103): 1.42

 – Late-infantile (n = 28): 0.52

 – Juvenile (n = 41): 0.51

 – Adult (n = 23): 0.24

 – Unspecified (n = 11): 0.15

Hult et al. [32]/retrospective cohort (good)

Sweden

• Quantitative and qualitative determination of urinary glycosaminoglycans and oligosaccharides

• Determination of enzyme activities

1.73 (excluding prenatal diagnosis)

Pinto et al. [44]/retrospective cohort (moderate)

Portugal

• Enzymatic activity determined in a blood sample and subsequently confirmed in cultured skin fibroblasts

• Urinary excretion of substrates

• Genotype analysis

All MLD (N = 21): 1.85

 – Late-infantile (n = 11): 1.12

 – Juvenile (n = 2): 0.29

 – Adult (n = 7): 0.45

Stellitano et al. [48]/prospective cohort (pediatric population) (moderate)

UK

• Not specified

0.58

North America

Applegarth et al. [30]/cross-sectional (good)

Canada

• Appropriate criteria for diagnosis of a genetically inherited metabolic disease included appropriate family studies of the metabolic defect

• Laboratory tests

   – Quantitative plasma and CSF amino acid analyses

   – Urine organic acids by gas chromatography–mass spectrometry

   – Specific enzyme assays

   – Prenatal diagnosis

0.58

Asia–Pacific

Koto et al. [39]/cross-sectional (moderate)

Japan

• For late-infantile MLD (representing most part of sample size):

   – enzyme activity test (86.7%^b)

   – genetic testing (53.3%^b)

0.16

Chin et al. [31]/retrospective cohort (good)

Australia

• Biochemical assessments

   – Deficient enzyme

   – Elevated substrate biomarkers

• Molecular genetic testing that identified pathogenic variants

All MLD: 1.03

 – Postnatal: 1.00

Meikle et al. [33]/retrospective cohort (good)

Australia

• Enzymatic analysis

All MLD: 1.09 (equivalent to 1 per 92,000, as per publication)

 – Postnatal: 0.83 (equivalent to 1 per 121,000, as per publication)

South America

Giugliani et al. [37]/retrospective cohort (moderate)

Brazil

• Quantitation and electrophoresis of urinary glycosaminoglycans

• Specific fluorometric, colorimetric or radio isotopic enzyme assays and/or by identification of pathogenic variations in blood or fibroblasts cultivated from skin biopsies

0.21

Middle East

Al-Jasmi et al. [29]/retrospective cohort (good)

United Arab Emirates

• Clinical presentation

• Biochemical analysis performed at two referral centers

1.5

Ozkara et al. [43]/retrospective cohort (pediatric population) (moderate)

Turkey

• Enzyme deficiency

   – Postnatal diagnosis: leukocytes sample

   – Prenatal diagnosis: chorionic villus, amnion cell culture and cord blood samples

1.43