Table 2.
Studies reporting estimates of birth prevalence of MLD
| Reference/study design (qualitya) | Country | Sample size | MLD case identification method/diagnostic criteria | Birth prevalence (per 100,000 live births) |
|---|---|---|---|---|
| Europe | ||||
| Ługowska et al. [41]/retrospective cohort (moderate) | Poland | 60 | • 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 | 125 |
• 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 | 25 |
• 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 | 103 | • 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 | 47 |
• 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 | 21 |
• 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 | 76 | • Not specified | 0.58 |
| North America | ||||
| Applegarth et al. [30]/cross-sectional (good) | Canada | 6 |
• 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 | 24 |
• 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 | 38 |
• 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 | 46 | • 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 | 150 |
• 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 | 3 |
• Clinical presentation • Biochemical analysis performed at two referral centers |
1.5 |
| Ozkara et al. [43]/retrospective cohort (pediatric population) (moderate) | Turkey | 93 |
• Enzyme deficiency – Postnatal diagnosis: leukocytes sample – Prenatal diagnosis: chorionic villus, amnion cell culture and cord blood samples |
1.43 |
ARSA arylsulfatase A gene; ASA arylsulfatase A; CI confidence interval; CSF cerebrospinal fluid; CT computed tomography; MLD metachromatic leukodystrophy; MRI magnetic resonance imaging
aBased on the JBI checklist. Good methodological quality: 7–9 items met on the JBI checklist; moderate methodological quality: 4–6 items met on the JBI checklist; low methodological quality: 0–3 items met on the JBI checklist
bPercentages represent the proportion of patients who received a diagnosis with each method