DOI: 10.1212/WNL.0000000000010367 Neurology Publish Ahead … · 2020-07-17 · Pantaleoni, MD1, Anna Ardissone , MD5, Cinzia Gellera, PhD 4, Laura Farina, MD2, 3 1 Developmental

Neurology Publish Ahead of PrintDOI: 10.1212/WNL.0000000000010367

Symmetrical abnormalities of the globi pallidi in Succinic Semialdehyde Dehydrogenase Deficiency

Silvia Esposito, MD, PhD1, Marco Moscatelli, MD2, Claudio Caccia, PhD4, Elisa Granocchio, MD1, Chiara

Pantaleoni, MD1, Anna Ardissone , MD5 , Cinzia Gellera, PhD 4, Laura Farina, MD2, 3

1 Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11,

20131 Milan, Italy

2 Neuroradiology Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20131

Milan, Italy

3Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Via Ardeatina, 306/354, 00142 Rome, Italy

4Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via

Celoria 11, 20131 Milan, Italy

5Unit of Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20131

Milan, Italy

Corresponding author:

Silvia Esposito ([email protected])

Neurology® Published Ahead of Print articles have been peer reviewed and accepted for

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Published Ahead of Print on July 17, 2020 as 10.1212/WNL.0000000000010367

Title character count: 96 (including spaces and punctuation)

Word count of paper: 100

Number of Figures: 1

Word Count of Legend: 49

Key Words: Succinic semialdehyde dehydrogenase deficiency – SSADHD, metabolic disorder, MRI, Globi

Pallidi, GABA

Study funding: No targeted funding reported.

Disclosure: The authors report no disclosures relevant to the manuscript.

A 4‐year‐old boy born full term after an uneventful pregnancy and with normal early developmental

milestones achievement, presented hypotonia, motor coordination disorder, childhood apraxia of speech.

Brain MRI revealed globi pallidi T2 symmetrical signal abnormalities (Figure 1). An extensive diagnostic

workup panel was performed to excluded metabolic and acquired conditions.1,2 Urine organic acid profile

showed marked γ-hydroxybutyrate aciduria (222 µg/mg creatinine, n.v.<5). Genetic analysis revealed two

compound heterozygous pathogenic mutations in ALDH5A1 gene (p.Pro81Ser, maternal origin;

p.Arg527Ter, paternal origin) consistent with SSADHD suspicion. This rare entity must be suspected in

case of T2-weighted MRI symmetrical abnormalities of the globi pallidi.1,2

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Appendix 1: Authors

Name Location Contribution

Silvia Esposito, MD, PhD

Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

study design and manuscript writing, cared for the patient

Marco Moscatelli, MD

Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

interpretation of radiological images, and manuscript revision for intellectual content

Claudio Caccia, PhD

Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

manuscript revision for intellectual content and interpretation of metabolic and genetic findings

Elisa Granocchio, MD Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

manuscript revision for intellectual content and interpretation of neuropsychological assessment

Chiara Pantaleoni, MD Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

manuscript revision for intellectual content

Anna Ardissone, MD Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

manuscript revision for intellectual content, cared for the patient

Cinzia Gellera, PhD Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

manuscript revision for intellectual content and interpretation of metabolic and genetic findings

Laura Farina, MD Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy Fondazione IRCCS Fondazione Santa Lucia, Rome, Italy

interpretation of radiological images and manuscript revision for intellectual content

Teaching Slides-http://links.lww.com/WNL/B174

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References

1: Barkovich AJ. An approach to MRI of metabolic disorders in children. J Neuroradiol. 2007 May;34(2):75-

88. Review. PubMed PMID: 17459477.

2: Zuccoli G, Yannes MP, Nardone R, Bailey A, Goldstein A. Bilateral symmetrical basal ganglia and

thalamic lesions in children: an update (2015). Neuroradiology. 2015 Oct;57(10):973-89. doi:

10.1007/s00234-015-1568-7. PubMed PMID: 26227169.

Figure Title

Globi Pallidi T2 symmetrical hyperintensity

Figure Legend

Figure1: Axial (A) and coronal T2-wi (B-C) show symmetrical hyperintensity of the globi pallidi (arrows).

Note that both pallidal components (internal and external pallidus) are well discernible. No dentate

involvement nor cerebellar atrophy is seen. D) DWI images show pallidal diffusion restriction at high b-

values confirmed by ADC map (E).

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DOI 10.1212/WNL.0000000000010367 published online July 17, 2020Neurology 

Silvia Esposito, Marco Moscatelli, Claudio Caccia, et al. Semialdehyde Dehydrogenase Deficiency

Teaching NeuroImages: Symmetrical abnormalities of the globi pallidi in Succinic

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