Neuropediatrics 2019; 50(05): 313-317
DOI: 10.1055/s-0039-1693148
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

Bilateral Striatal Necrosis with Polyneuropathy with a Novel SLC25A19 (Mitochondrial Thiamine Pyrophosphate Carrier OMIMI*606521) Mutation: Treatable Thiamine Metabolic Disorder—A Report of Two Indian Cases

Vykuntaraju K. Gowda
1   Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India
,
Varunvenkat M. Srinivasan
1   Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India
,
Kapil Jehta
1   Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India
,
Maya D. Bhat
2   Department of Neuroradiology, National Institute of Mental Health and Neurosciences, Bangalore, India
› Author Affiliations
Funding None.
Further Information

Publication History

02 October 2018

17 May 2019

Publication Date:
11 July 2019 (online)

Abstract

BackgroundSLC25A19 gene mutations cause Amish congenital lethal microcephaly and bilateral striatal necrosis with polyneuropathy. We are reporting two cases of bilateral striatal necrosis with polyneuropathy due to SLC25A19 gene mutations.

Methods A 36-month-old boy and a 5-year-old girl, unrelated, presented with recurrent episodes of flaccid paralysis and encephalopathy following nonspecific febrile illness. Examination showed dystonia and absent deep tendon reflexes.

Results Nerve conduction studies showed an axonal polyneuropathy. Magnetic resonance imaging (MRI) of the brain in both cases showed signal changes in the basal ganglia. Next-generation sequencing revealed a novel homozygous missense variation c.910G>A (p.Glu304Lys) in the SLC25A19 gene in the boy and a homozygous mutation c.869T > A (p. Leu290Gln) in the SLC25A19 gene in the girl. Mutations were validated by Sanger sequencing, and carrier statuses of parents of both children were confirmed. Both children improved with thiamine supplementation.

Conclusion If any child presents with recurrent encephalopathy with flaccid paralysis, dystonia, and neuropathy, a diagnosis of bilateral striatal necrosis with polyneuropathy due to SLC25A19 mutations should be considered and thiamine should be initiated.

Contributions

V. R. revised and approved the manuscript for important intellectual content and guarantor of the paper. V. S. contributed to the diagnosis, management, and writing of the manuscript. K. J. conducted laboratory tests and analyzed the data. M. B. contributed to the drafting of the manuscript, supervision of the work, and revision of the manuscript.


 
  • References

  • 1 Goutières F, Aicardi J. Acute neurological dysfunction associated with destructive lesions of the basal ganglia in children. Ann Neurol 1982; 12 (04) 328-332
  • 2 Zevit N, Steinmetz A, Kornreich L, Straussberg R. Acute infantile bilateral striatal necrosis: single-photon emission computed tomography (SPECT) imaging and review. J Child Neurol 2007; 22 (10) 1222-1226
  • 3 Strauss KA, Morton DH. Type I glutaric aciduria, part 2: a model of acute striatal necrosis. Am J Med Genet C Semin Med Genet 2003; 121C (01) 53-70
  • 4 Ozand PT, Gascon GG, Al Essa M. , et al. Biotin-responsive basal ganglia disease: a novel entity. Brain 1998; 121 (Pt 7): 1267-1279
  • 5 Basel-Vanagaite L, Muncher L, Straussberg R. , et al. Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis. Ann Neurol 2006; 60 (02) 214-222
  • 6 Spiegel R, Shaag A, Edvardson S. , et al. SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis. Ann Neurol 2009; 66 (03) 419-424
  • 7 Ortigoza-Escobar JD, Alfadhel M, Molero-Luis M, Darin N, Spiegel R. , et al. Thiamine deficiency in childhood with attention to genetic causes: survival and outcome predictors. Ann Nerol 2017; 82: 317-30
  • 8 Gowda V RKN, Shivananda GM, Sankyan N. Thiamine responsive megaloblastic anemia in three Indian children. Indian J Pediatr 2011; 78: 888-889
  • 9 Gowda VK, Srinivasan VM, Bhat M, Benakappa N. Biotin thiamine responsive basal ganglia disease in siblings- treatable cause of generalized dystonia. Indian J Pediatr 2018; 85 (02) 155-157
  • 10 Foulon V, Antonenkov VD, Croes K. , et al. Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids. Proc Natl Acad Sci U S A 1999; 96 (18) 10039-10044
  • 11 Kelley RI, Robinson D, Puffenberger EG, Strauss KA, Morton DH. Amish lethal microcephaly: a new metabolic disorder with severe congenital microcephaly and 2-ketoglutaric aciduria. Am J Med Genet 2002; 112 (04) 318-326