Saposin B–Deficient Metachromatic Leukodystrophy Mimicking Acute Flaccid Paralysis

Madaan, Priyanka; Jauhari, Prashant; Chakrabarty, Biswaroop; Kumar, Atin; Gulati, Sheffali

doi:10.1055/s-0039-1692646

Cited by 8 publications

(6 citation statements)

References 13 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There have been two previous reports of MLD due to Sap‐B deficiency from India. In both cases, the variant c.679_681delAAG in exon 6 of the PSAP gene was identified 8,9 . Both these patients presented with the late‐infantile form.…”

Section: Discussionmentioning

confidence: 87%

“…To date, a total of 12 variants in the PSAP gene have been reported in 30 MLD patients worldwide 1 . In India, two cases of MLD due to Sap‐B deficiency have been reported 8,9 . Both were late infantile forms and showed the presence of the variant c.679_681delAAG in exon 6 of the PSAP gene.…”

Section: Introductionmentioning

confidence: 99%

“… 1 In India, two cases of MLD due to Sap‐B deficiency have been reported. 8 , 9 Both were late infantile forms and showed the presence of the variant c.679_681delAAG in exon 6 of the PSAP gene. The severity of the condition is governed by the type of variant.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Late infantile and adult‐onset metachromatic leukodystrophy due to novel missense variants in the PSAP gene: Case report from India

et al. 2023

View full text Add to dashboard Cite

Metachromatic leukodystrophy (MLD) due to Sap-B deficiency is a rare autosomal recessive disorder caused due to biallelic variants in the PSAP gene. The PSAP gene encodes a precursor protein prosaposin, which is subsequently cleaved to form four active glycoproteins: Sap-A, Sap-B, Sap-C, and Sap-D. In case of deficiency of the sphingolipid activator protein Sap-B, there is a gradual accumulation of cerebroside-3-sulfate in the myelin of the nervous system resulting in progressive demyelination. Only 12 variants have been reported in the PSAP gene causing Sap-B deficiency to date. Here, we report two cases of MLD due to Sap-B deficiency (late-infantile and adult-onset form) harboring two novel missense variants c.688T > G and c.593G > A in the PSAP gene respectively. This study reports the third case of adult-onset MLD due to Sap-B deficiency in the world. The proband, a 3-year-old male child presented with complaints of hypotonia, lower limb tremors and global developmental delay. His MRI showed hyperintense signals in the bilateral cerebellar white matter. Overall, the findings were suggestive of metachromatic leukodystrophy. The second case was a 19-year-old male child with clinical features of regression of speech, gait ataxia and bilateral tremors referred to our clinic. MRI data suggested metachromatic leukodystrophy. Normal enzyme activity of arylsulfatase-A led to a suspicion of saposin B deficiency. For both cases, targeted sequencing was performed. This identified homozygous variant c.688T > G (p.Cys230Gly) and c.593G > A (p.Cys198Tyr) in exon 6 of the PSAP gene, respectively.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Late infantile and adult‐onset metachromatic leukodystrophy due to novel missense variants in the PSAP gene: Case report from India

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Other variants, such as the missense variants c.1283C > T (the most common variant in adult MLD), result in ASA that retains some residual activity. Atypical MLD due to saposin B deficiency is caused by pathogenic variants in the prosaposin gene [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

A systematic review on the birth prevalence of metachromatic leukodystrophy

Chang,

Bergamasco,

Bonnin

et al. 2024

Orphanet J Rare Dis

View full text Add to dashboard Cite

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.

show abstract

“…6,7 Besides, there have been studies on use of KD in infants with DRE and in children with refractory status epilepticus. [8][9][10] Various dietary therapies for DRE encompass different KDs, including classic KD, KD with lower ketogenic ratios, and medium-chain triglyceride KD (MCT-KD) and less restrictive diets such as MAD, and LGIT. 11,12 The classic KD, with a ketogenic ratio of 4:1, derives 80% of total energy intake from fat (mostly long-chain triglycerides; mediumchain triglycerides in MCT-KD) and the rest from carbohydrate and protein combined.…”

mentioning

confidence: 99%

Efficacy and Safety of Dietary Therapies for Childhood Drug-Resistant Epilepsy

et al. 2023

View full text Add to dashboard Cite

ImportanceDespite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions.ObjectiveTo evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy.Data SourcesSystematic review and network meta-analysis (frequentist) of studies in PubMed, Embase, Cochrane, and Ovid published from inception to April 2022 using the search terms ketogenic diet, medium chain triglyceride diet, modified Atkins diet, low glycemic index therapy, and refractory epilepsy.Study SelectionRandomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) with each other or care as usual in childhood drug-resistant epilepsy were included. Abstract, title, and full text were screened independently by 2 reviewers.Data Extraction and SynthesisData extraction was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Cochrane risk-of-bias tool was used to assess the study quality. Effect sizes were calculated as odds ratio with 95% CI using random-effects model. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve.Main Outcomes and MeasuresShort-term (≤3 months) 50% or higher and 90% or higher reduction in seizure frequency and treatment withdrawal due to adverse events were the primary efficacy and safety outcomes.ResultsOf 2158 citations, 12 randomized clinical trials (907 patients) qualified for inclusion. In the short term, all dietary interventions were more efficacious than care as usual for 50% or higher seizure reduction (low glycemic index therapy: odds ratio [OR], 24.7 [95% CI, 5.3-115.4]; modified Atkins diet: OR, 11.3 [95% CI, 5.1-25.1]; ketogenic diet: OR, 8.6 [95% CI, 3.7-20.0]), while ketogenic diet (OR, 6.5 [95% CI, 2.3-18.0]) and modified Atkins diet (OR, 5.1 [95% CI, 2.2-12.0]) were better than care as usual for seizure reduction of 90% or higher. However, adverse event–related discontinuation rates were significantly higher for ketogenic diet (OR, 8.6 [95% CI, 1.8-40.6]) and modified Atkins diet (OR, 6.5 [95% CI, 1.4-31.2]) compared with care as usual. Indirectly, there was no significant difference between dietary therapies in efficacy and safety outcomes.Conclusions and RelevanceThis study found that all dietary therapies are effective in the short term. However, modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet. Direct head-to-head comparison studies are needed to confirm these findings.

show abstract

Saposin B–Deficient Metachromatic Leukodystrophy Mimicking Acute Flaccid Paralysis

Cited by 8 publications

References 13 publications

Late infantile and adult‐onset metachromatic leukodystrophy due to novel missense variants in the PSAP gene: Case report from India

Late infantile and adult‐onset metachromatic leukodystrophy due to novel missense variants in the PSAP gene: Case report from India

A systematic review on the birth prevalence of metachromatic leukodystrophy

Efficacy and Safety of Dietary Therapies for Childhood Drug-Resistant Epilepsy

Contact Info

Product

Resources

About