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Open Access Green as soon as Postprint is submitted to ZB.
Mitochondrial transporter defects: Successful treatment with ketogenic diet therapy
Vortrag: (2021)
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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Publication type
Other: Lecture
ISSN (print) / ISBN
0174-304X
e-ISSN
1439-1899
Journal
Neuropediatrics
Quellenangaben
Pages: S1-S53
Publisher
Thieme
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Human Genetics (IHG)