Disease Heterogeneity in Na+/Citrate Cotransporter Deficiency

  • Irina Anselm
  • Morgan MacCuaig
  • Sanjay B. Prabhu
  • Gerard T. Berry
Case Report
Part of the JIMD Reports book series (JIMD, volume 31)

Abstract

We report a novel mutation found in two siblings, a male and a female aged 8 and 5 years, respectively. Both patients presented with developmental delay and intractable seizures consistent with previous reports of SLC13A5 transporter deficiency. Both had two mutations in the SLC13A5 gene, c.655G>A (G219R) and the novel mutation c.245A>G (Y82C). However, the phenotypes were not identical as the female had focal cortical dysplasia that led to brain surgery. This is another example of the heterogeneity in disease expression even when the genotype is identical in the affected individuals.

References

  1. Edvardson S, Porcelli V, Jalas C et al (2013) Agenesis of corpus callosum and optic nerve hypoplasia due to mutations in SLC25A1 encoding the mitochondrial citrate transporter. J Med Genet 50:240–245CrossRefPubMedGoogle Scholar
  2. Hardies K, de Kovel CG, Weckhuysen S et al (2015) Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain 138(Pt 11):3238–3250Google Scholar
  3. Inoue K, Zhuang L, Ganapathy V (2002) Human Na+ -coupled citrate transporter: primary structure, genomic organization, and transport function. Biochem Biophys Res Commun 299:465–471CrossRefPubMedGoogle Scholar
  4. Mroch AR, Laudenschlager M, Flanagan JD (2012) Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency. Am J Med Genet A 158A:155–158CrossRefPubMedGoogle Scholar
  5. Shevell MI, Matthews PM, Scriver CR et al (1994) Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency. Pediatr Neurol 11:224–229CrossRefPubMedGoogle Scholar
  6. Siu VM, Ratko S, Prasad AN, Prasad C, Rupar CA (2010) Amish microcephaly: long-term survival and biochemical characterization. Am J Med Genet A 152A:1747–1751CrossRefPubMedGoogle Scholar
  7. Thevenon J, Milh M, Feillet F et al (2014) Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life. Am J Hum Genet 95:113–120CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Irina Anselm
    • 1
  • Morgan MacCuaig
    • 2
  • Sanjay B. Prabhu
    • 3
  • Gerard T. Berry
    • 4
  1. 1.Department of Neurology, Harvard Medical SchoolBoston Children’s HospitalBostonUSA
  2. 2.Department of NeurologyBoston Children’s HospitalBostonUSA
  3. 3.Department of Radiology, Harvard Medical SchoolBoston Children’s HospitalBostonUSA
  4. 4.Division of Genetics and Genomics, Department of Pediatrics, Harvard Medical SchoolBoston Children’s HospitalBostonUSA

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