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. 2024 Feb 21;19(1):80.
doi: 10.1186/s13023-024-03044-w.

A systematic review on the birth prevalence of metachromatic leukodystrophy

Shun-Chiao Chang  1 , Aurore Bergamasco  2 , Mélanie Bonnin  2 , Teigna Arredondo Bisonó  2 , Yola Moride  3
Affiliations

A systematic review on the birth prevalence of metachromatic leukodystrophy

Shun-Chiao Chang et al. Orphanet J Rare Dis. .

Abstract

Background: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency in arylsulfatase A (ASA) activity arising primarily from ASA gene (ARSA) variants. Late-infantile, juvenile and adult clinical subtypes are defined by symptom onset at ≤ 2.5, > 2.5 to < 16 and ≥ 16 years, respectively. Epidemiological data were sought to address knowledge gaps and to inform decisions regarding the clinical development of an investigational drug.

Methods: To synthesize all available estimates of MLD incidence and birth prevalence worldwide and in selected countries, Ovid MEDLINE and Embase were searched systematically (March 11, 2022) using a population, intervention, comparator, outcome, time and setting framework, complemented by pragmatic searching to reduce publication bias. Where possible, results were stratified by clinical subtype. Data were extracted from non-interventional studies (clinical trials, non-clinical studies and case reports were excluded; reviews were used for snowballing only).

Results: Of the 31 studies included, 14 reported birth prevalence (13 countries in Asia-Pacific, Europe, the Middle East, North America and South America), one reported prevalence and none reported incidence. Birth prevalence per 100,000 live births ranged from 0.16 (Japan) to 1.85 (Portugal). In the three European studies with estimates stratified by clinical subtypes, birth prevalence was highest for late-infantile cases (0.31-1.12 per 100,000 live births). The distribution of clinical subtypes reported in cases diagnosed over various time periods in 17 studies varied substantially, but late-infantile and juvenile MLD accounted for at least two-thirds of cases in most studies.

Conclusions: This review provides a foundation for further analysis of the regional epidemiology of MLD. Data gaps indicate the need for better global coverage, increased use of epidemiological measures (e.g. prevalence estimates) and more stratification of outcomes by clinical and genetic disease subtype.

Keywords: Arylsulfatase A; Birth prevalence; Epidemiology; Lysosomal storage disease; Metachromatic leukodystrophy; Systematic review.

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Conflict of interest statement

S-CC is an employee of Takeda Development Center Americas, Inc. and is a stockholder of Takeda Pharmaceutical Company Limited. AB, MB, TAB and YM have participated in advisory boards or are consultants for Takeda and are employees of YOLARX Consultants.

Figures

Fig. 1
Fig. 1
PRISMA flow chart of the systematic review process. DEF data extraction form; PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analysis
Fig. 2
Fig. 2
Regional birth prevalence of MLD. Birth prevalence refers to the number of new MLD diagnoses (prenatal and postnatal) divided by the number of live births over a specified period. aOnly postnatal diagnoses were considered; prenatal diagnoses were excluded owing to a lack of complete data. MLD metachromatic leukodystrophy
Fig. 3
Fig. 3
Distribution of MLD diagnoses according to clinical subtype. MLD metachromatic leukodystrophy
See this image and copyright information in PMC

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