Neuropediatrics 2021; 52(S 01): S1-S53
DOI: 10.1055/s-0041-1739697
Freier Vortrag

Mitochondrial Transporter Defects: Successful Treatment with Ketogenic Diet Therapy

Bigna K. Bölsterli
1   Department of Neuropediatrics, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
2   Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
,
Eugen Boltshauser
1   Department of Neuropediatrics, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
2   Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
,
Felix Distelmaier
3   Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
,
Tobias Geis
4   Department of Pediatric Neurology, Klinik St. Hedwig, University Children's Hospital Regensburg (KUNO), Regensburg, Germany
,
Annick Klabunde-Cherwon
5   Division of Paediatric Epileptology, Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany
,
Raimund Kottke
2   Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
6   Department of Diagnostic Imaging, University Children's Hospital Zurich, University of Zurich, Switzerland
,
Christine Makowski
7   Department for Paediatric Adolescent Medicine and Neonatology, Munich Clinic, Schwabing Hospital and Technical University of Munich, School of Medicine, Munich, Germany
,
Johannes A. Mayr
8   University Children's Hospital, Paracelsus Medical University, Salzburg, Austria
,
Ruth L. O’Gorman Tuura
2   Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
9   Center for MR Research, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
,
Holger Prokisch
10   Institute of Human Genetics, Technical University of Munich, Munich, Germany
11   Institute of Human Genetics, Helmholtz Zentrum München, Munich, Germany
,
Katja Steinbruecker
8   University Children's Hospital, Paracelsus Medical University, Salzburg, Austria
,
Robert Steinfeld
1   Department of Neuropediatrics, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
2   Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
,
Steffen Syrbe
5   Division of Paediatric Epileptology, Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany
,
Matias Wagner
10   Institute of Human Genetics, Technical University of Munich, Munich, Germany
12   Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany
,
Andreas Ziegler
13   Division of Pediatric Neurology and Metabolic Medicine, Centre for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany
,
Saskia Wortmann
8   University Children's Hospital, Paracelsus Medical University, Salzburg, Austria
14   Radboud Centre for Mitochondrial Medicine (RCMM), Amalia Children's Hospital, Radboudumc, Nijmegen, The Netherlands
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    Background/Purpose: No causal treatment for mitochondrial disease exists. Exome sequencing allows to identify specific mitochondrial defects (theoretically) amenable to dietary intervention. The mitochondrial transporters aspartate glutamate carrier 1 (AGC1) and mitochondrial pyruvate carrier 1 (MPC1) are tightly linked to glucose catabolism. Successful pathomechanism-based treatment of such defects with ketogenic diet (KD) was reported in two patients with AGC1-deficiency and a MPC1-deficient mouse model.

    Methods: The Munich exome database was queried for AGC1- and MPC1-deficient patients. Clinical and neuroradiological details were collected and literature cases reviewed.

    Results: Six MPC1-deficient individuals (4 reported, 2 novel) were identified and outcome on KD reported in 2 (1 novel). The phenotype beside developmental impairment (6/6) and elevated serum lactate (6/6) was variable with epilepsy (3/6), microcephaly (3/6), and the first report of one patient with splenomegaly, diabetes mellitus and bone fractures. In contrast to the previously reported infant, our severely affected patient improved distinctly on KD, with seizure freedom and developmental progress.

    Thirteen AGC1-deficient individuals (8 reported, 5 novel) were identified. Seven of 13 received KD. All had infantile-onset epilepsy, severe developmental impairment and muscular hypotonia. MRI revealed brain atrophy (9/9) and reduced myelination (7/9), MRS showed reduced n-acetyl-aspartate (5/6). Elevated serum lactate was found in 8 of 13. In six of seven patients, KD showed impressive improvement on seizure frequency, development, and neuroradiological features.

    Conclusion: Treatment with KD is beneficial in patients with AGC1 and MPC1 deficiency. This underlines the importance for early genetic diagnostics in patients with epilepsy especially with additional markers raising suspicion of mitochondrial disease.


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    Die Autoren geben an, dass kein Interessenkonflikt besteht.

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    Artikel online veröffentlicht:
    28. Oktober 2021

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