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Neuropediatrics 2023; 54(03): 211-216
DOI: 10.1055/a-2018-4845
Short Communication

Recurrent Sensory-Motor Neuropathy Mimicking CIDP as Predominant Presentation of PDH Deficiency

Carolina Croci 
1   Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy
,
Matteo Cataldi
2   Department of Child Neuropsychiatry, IRCCS Istituto Giannina Gaslini, Genova, Italy
,
Serena Baratto
3   Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genova, Italy
,
Claudio Bruno
1   Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy
3   Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genova, Italy
,
Federica Trucco
4   Department of Neurorehabilitation, University of Milan, Milan, Italy
,
Stefano Doccini
5   Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, Pisa, Italy
,
Alessandro Romano
6   Experimental Neuropathology Unit, Division of Neuroscience, Institute of Experimental Neurology, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy
,
Claudia Nesti
5   Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, Pisa, Italy
,
Filippo Maria Santorelli
5   Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, Pisa, Italy
,
Chiara Fiorillo
1   Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy
2   Department of Child Neuropsychiatry, IRCCS Istituto Giannina Gaslini, Genova, Italy
› Author Affiliations Funding This work received partial support from AFM grant 22431 to CF and from Italian Ministry of Health “Ricerca Corrente.” F.M.S., S.D., and C.N. are supported in part by a grant from the Italian Ministry of Health, Ricerca Corrente 2021 5 × 1000.
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Abstract

Introduction Pyruvate dehydrogenase complex (PDH) deficiency (Online Mendelian Inheritance in Man # 312170) is a relatively common mitochondrial disorder, caused by mutations in the X-linked PDHA1 gene and presenting with a variable phenotypic spectrum, ranging from severe infantile encephalopathy to milder chronic neurological disorders.

Isolated peripheral neuropathy as predominant clinical presentation is uncommon.

Results We report on a patient, now 21 years old, presenting at the age of 2 years with recurrent symmetric weakness as first symptom of a PDH deficiency. Neurophysiological evaluation proving a sensory-motor polyneuropathy with conduction blocks and presence of elevated cerebrospinal fluid proteins, suggested a chronic inflammatory demyelinating polyneuropathy. The evidence of high serum lactate and the alterations in oxidative metabolism in muscle biopsy pointed toward the final diagnosis. After starting nutritional supplements, no further episodes occurred. A hemizygous mutation in PDHA1 (p.Arg88Cys) was identified. This mutation has been previously described in five patients with a similar phenotype. A three-dimensional reconstruction demonstrated that mutations affecting this arginine destabilize the interactions between the subunits of the E1 complex.

Conclusion We summarize the clinical and genetic characteristics of one patient with PDH deficiency presenting isolated peripheral nervous system involvement. This study highlights that the diagnosis of PDH deficiency should be considered in children with unexplained peripheral neuropathy, even with features suggestive of acquired forms, especially in case of early onset and limited response to treatment. A simple analysis of lactic acid could help to target the diagnosis.

In addition, we suggest that the residue Arg88 is the most frequently involved in this specific phenotype of PDH deficiency.

Keywords

PDHA1 mutation - PDH deficiency - peripheral neuropathy - episodic weakness - mitochondrial disorder

Ethical Consideration

Patient and family signed informed consent for research use of clinical data and publication of photographic material.


Authors' Contributions

C.C.: acquisition and analysis of data, drafting the manuscript.


M.C.: acquisition and analysis of neurophysiological data.


S.B.: acquisition and analysis of muscle biopsy data.


C.B.: acquisition and analysis of clinical data.


C.N.: acquisition and analysis of genetic data, drafting the manuscript.


F.M.S.: acquisition and analysis of genetic data, drafting the manuscript.


S.D.: acquisition and analysis of biochemical data.


A.R.: Three-dimensional modeling and bioinformatics data.


C.F.: conception and design of the study, drafting the manuscript.


Supplementary Material



Publication History

Accepted Manuscript online:
24 January 2023

Article published online:
07 March 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
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