Download PDF
Neuropediatrics 2019; 50(05): 318-321
DOI: 10.1055/s-0039-1692646
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

Saposin B–Deficient Metachromatic Leukodystrophy Mimicking Acute Flaccid Paralysis

Priyanka Madaan
1   Department of Pediatrics, Child Neurology Division, All India Institute of Medical Sciences, New Delhi, India
,
Prashant Jauhari
1   Department of Pediatrics, Child Neurology Division, All India Institute of Medical Sciences, New Delhi, India
,
Biswaroop Chakrabarty
1   Department of Pediatrics, Child Neurology Division, All India Institute of Medical Sciences, New Delhi, India
,
Atin Kumar
2   Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
,
Sheffali Gulati
1   Department of Pediatrics, Child Neurology Division, All India Institute of Medical Sciences, New Delhi, India
› Author Affiliations Source of funding None.
Further Information

Publication History

04 January 2019

03 May 2019

Publication Date:
18 July 2019 (online)

Also available at
    Permissions and Reprints

Abstract

Metachromatic leukodystrophy (MLD) is a rare sphingolipid storage disorder caused by arylsulfatase A (ARSA) deficiency, resulting in central and peripheral demyelination. However, an uncommon form of MLD caused by saposin B deficiency is also described (around 10 mutations reported till date). MLD is a systemic disorder affecting the central and peripheral nervous system, gall bladder, and kidneys. Acute flaccid paralysis as the initial clinical presentation is previously known in ARSA-deficient MLD. Hereby, we report a child with acute flaccid paralysis with brain magnetic resonance imaging showing nonspecific periventricular leukodystrophy. He had progressive cognitive decline with gall bladder polyposis. ARSA levels were within normal limits. Leukodystrophy gene panel revealed a homozygous pathogenic deletion (Lys227del variant) in prosaposin (PSAP) gene. Hence, a final diagnosis of saposin B–deficient MLD was established. The index case highlights the importance of clinical and electrophysiological clues in the diagnosis of such atypical presentations of MLD.

Keywords

metachromatic leukodystrophy - saposin B - peripheral neuropathy - acute flaccid paralysis - gall bladder polyposis
 

  • References

  • 1 von Figura K, Gieselmann V, Jaeken J. Metachromatic leukodystrophy. In: Scriver CR, Beaudet AL, Sly WS, Valle D. , eds. The metabolic and molecular bases of inherited diseases. New York, NY: McGraw Hill; 2001: 3695-3724
    Search in Google Scholar
  • 2 Kolnikova M, Jungova P, Skopkova M. , et al. Late infantile metachromatic leukodystrophy due to novel pathogenic variants in the PSAP gene. J Mol Neurosci 2019; 67 (04) 559-563
    CrossrefPubMedSearch in Google Scholar
  • 3 Richards S, Aziz N, Bale S. , et al; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (05) 405-424
    Search in Google Scholar
  • 4 Cesani M, Lorioli L, Grossi S. , et al. Mutation update of ARSA and PSAP genes causing metachromatic leukodystrophy. Hum Mutat 2016; 37 (01) 16-27
    CrossrefPubMedSearch in Google Scholar
  • 5 Rorman EG, Scheinker V, Grabowski GA. Structure and evolution of the human prosaposin chromosomal gene. Genomics 1992; 13 (02) 312-318
    CrossrefPubMedSearch in Google Scholar
  • 6 Sandhoff K, Kolter T, Harzer K. Sphingolipid activator proteins. In: Scriver CR, Beaudet AL, Valle D, Sly WS. , eds. The Metabolic and Molecular Bases of Inherited Diseases. New York, NY: McGraw-Hill; 2001: 3371-3388
    Search in Google Scholar
  • 7 Lorioli L, Cesani M, Regis S. , et al. Critical issues for the proper diagnosis of Metachromatic Leukodystrophy. Gene 2014; 537 (02) 348-351
    CrossrefPubMedSearch in Google Scholar
  • 8 Martinez AC, Ferrer MT, Fueyo E, Galdos L. Peripheral neuropathy detected on electrophysiological study as first manifestation of metachromatic leucodystrophy in infancy. J Neurol Neurosurg Psychiatry 1975; 38 (02) 169-174
    CrossrefPubMedSearch in Google Scholar
  • 9 Bindu PS, Mahadevan A, Taly AB, Christopher R, Gayathri N, Shankar SK. Peripheral neuropathy in metachromatic leucodystrophy. A study of 40 cases from south India. J Neurol Neurosurg Psychiatry 2005; 76 (12) 1698-1701
    CrossrefPubMedSearch in Google Scholar
  • 10 Dubey R, Chakrabarty B, Gulati S. , et al. Leukodystrophy presenting as acute-onset polyradiculoneuropathy. Pediatr Neurol 2014; 50 (06) 616-618
    CrossrefPubMedSearch in Google Scholar
  • 11 Deeg KH, Reif R, Stehr K, Hümmer KP, Harzer K. [Chronic hemorrhagic pancreatitis in gallbladder polyposis as an initial symptom of metachromatic leukodystrophy]. Monatsschr Kinderheilkd 1986; 134 (05) 272-275
    PubMedSearch in Google Scholar
  • 12 Ries M, Deeg KH. Polyposis of the gallbladder associated with metachromatic leukodystrophy. Eur J Pediatr 1993; 152 (05) 450-451
    CrossrefPubMedSearch in Google Scholar
  • 13 van Rappard DF, Bugiani M, Boelens JJ. , et al. Gallbladder and the risk of polyps and carcinoma in metachromatic leukodystrophy. Neurology 2016; 87 (01) 103-111
    CrossrefPubMedSearch in Google Scholar
  • 14 van Egmond ME, Pouwels PJ, Boelens JJ. , et al. Improvement of white matter changes on neuroimaging modalities after stem cell transplant in metachromatic leukodystrophy. JAMA Neurol 2013; 70 (06) 779-782
    CrossrefPubMedSearch in Google Scholar
  • 15 Boucher AA, Miller W, Shanley R. , et al. Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report. Orphanet J Rare Dis 2015; 10: 94
    CrossrefPubMedSearch in Google Scholar