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July 4, 2016
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Teaching NeuroImages: White matter hypomyelination and progressive calcifications in cerebral folate deficiency

Joost Nicolai, MD, PhD, Marjan J.A. van Kempen, PhD, and Alida A. Postma, MD, PhDAuthors Info & Affiliations
July 5, 2016 issue
87 (1) e4-e5
https://doi.org/10.1212/WNL.0000000000002805
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Cerebral folate transport deficiency is caused by homozygous or compound heterozygous mutations of the FOLR1 gene.1 Recently, we found a homozygous FOLR1 mutation (NM_016725.2: c.562C>G p.[Leu188Val]) in a 2.5-year-old boy with febrile and nonfebrile status epilepticus, progressive ataxia, and progressive MRI abnormalities. Until the diagnosis was made, serial MRI had been performed (figure). CSF analysis (5-methyltetrahydrofolate <2 nmol/L, normal >40 nmol/L) and magnetic resonance spectroscopy showing a low choline peak validated the pathogenicity of our findings.2
Figure MRI
MRI at age 1 year, 8 months (upper row) and at age 2 years, 9 months (lower row). White matter hyperintensity (*) at T2-weighted (left-sided) imaging is prominent but does not change evidently over time. An increase in the number of calcifications (arrows) at the gradient-echo images (right-sided) is mainly seen in the lentiform nuclei and peripheral white matter.
Nonprogressive hypomyelination is considered part of FOLR1,1,2 although no author has published serial MRI. Our data show that cerebral folate transport deficiency must be considered in hypomyelination and progressive calcifications.

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REFERENCES

1.
Grapp M, Just IA, Linnankivi T, et al. Molecular characterization of folate receptor 1 mutations delineates cerebral folate transport deficiency. Brain 2012;135:2022–2031.
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2.
Steinfeld R, Grapp M, Kraetzner R, et al. Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism. Am J Hum Genet 2009;85:354–363.
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PubMed
Google Scholar

Information & Authors

Information

Published In

Neurology®
Volume 87 • Number 1 • July 5, 2016
Pages: e4-e5
PubMed: 27378809

Copyright

© 2016 American Academy of Neurology.

Publication History

Published online: July 4, 2016
Published in print: July 5, 2016

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Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Study Funding

No targeted funding reported.

Authors

Affiliations & Disclosures

Joost Nicolai, MD, PhD
From the Departments of Neurology (J.N.) and Radiology (A.A.P.), Maastricht University Medical Center; and Department of Medical Genetics (M.J.A.v.K.), University Medical Center Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Dr Nicolai has received funding for congress visits from UCB Pharma and Actelion.
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
I participate as a speaker in a epilepsy course held by a non-profit organisation. I do receive honorarium for those lessons.
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
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Marjan J.A. van Kempen, PhD
From the Departments of Neurology (J.N.) and Radiology (A.A.P.), Maastricht University Medical Center; and Department of Medical Genetics (M.J.A.v.K.), University Medical Center Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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Alida A. Postma, MD, PhD
From the Departments of Neurology (J.N.) and Radiology (A.A.P.), Maastricht University Medical Center; and Department of Medical Genetics (M.J.A.v.K.), University Medical Center Utrecht, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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Notes

Correspondence to Dr. Nicolai: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Joost Nicolai: study concept and design, acquisition of data. Marjan J.A. van Kempen: analysis and interpretation of genetic data. Alida A. Postma: analysis and interpretation of MRI and MRS data.

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