Serial Magnetic Resonance Imaging (MRI) in Pyruvate Dehydrogenase Complex Deficiency

Shelkowitz, Emily; Fıçıcıoğlu, Can; Stence, Nicholas; Hove, Johan Van; Larson, Austin

doi:10.1177/0883073819881940

Cited by 10 publications

(12 citation statements)

References 30 publications

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“…33 It is believed that female patients with prenatal onset PDHA1related disease, due to severe mutations and lack of residual enzyme activity, display a nonprogressive course and that interventions such as a ketogenic diet would not be effective given the lack of responsiveness on a cellular basis. 12 In our study, two of seven female patients with prenatal developmental and clastic lesions (#7,9) showed progression on repeated MRI-s with additional postnatal lesions. It's is therefore possible that the pathophysiological mechanism could be more of continuum and that a ketogenic diet might be effective also in girls with developmental lesions as has been previously suggested.…”

Section: Discussionsupporting

confidence: 51%

“…The basal ganglia involvement in our study, with predominant involvement of the globi pallidi , is similar to previous studies 30,31 and differs from what has been described in other mitochondrial diseases where the lesions more commonly involve the striatum. Early diagnosis is important as the deep gray‐matter lesions could be reversible after introducing a ketogenic diet 4,12 …”

Section: Discussionmentioning

confidence: 99%

“…Early diagnosis is important as the deep gray-matter lesions could be reversible after introducing a ketogenic diet. 4,12 PDHA1 deficiency is an X-linked disorder leading to different manifestations between the sexes. In our cohort, there were more than twice as many females than males.…”

Section: Discussionmentioning

confidence: 99%

“…There are few research studies exploring the MRI phenotypes in PDHc deficiency, 11,12 with the existing knowledge originating mainly from case reports and smaller case series. Ventriculomegaly is the most frequent MRI finding, ranging from 35% to 85% in different cohorts 2,3,5 .…”

Section: Introductionmentioning

confidence: 99%

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Novel imaging findings in pyruvate dehydrogenase complex (PDHc) deficiency—Results from a nationwide population‐based study

Savvidou

Ivarsson

Naess³

et al. 2021

J of Inher Metab Disea

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The vast clinical and radiological spectrum of pyruvate dehydrogenase complex (PDHc) deficiency continues to pose challenges both in diagnostics and disease monitoring. Prompt diagnosis is important to enable early initiation of ketogenic diet. The patients were recruited from an ongoing population-based study in Sweden. All patients with a genetically confirmed diagnosis who had been investigated with an MRI of the brain were included. Repeated investigations were assessed to study the evolution of the MRI changes. Sixty-two MRI investigations had been performed in 34 patients (23 females). The genetic cause was mutations in PDHA1 in 29, PDHX and DLAT in 2 each, and PDHB in 1. The lesions were prenatal developmental in 16, prenatal clastic in 18, and postnatal clastic in 15 individuals. Leigh-like lesions with predominant

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Novel imaging findings in pyruvate dehydrogenase complex (PDHc) deficiency—Results from a nationwide population‐based study

Savvidou

Ivarsson

Naess³

et al. 2021

J of Inher Metab Disea

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“…KD treatment is therefore considered a treatment of choice for PDHC syndrome, and it has already been shown to lead to general improvements in some PDHC‐related neurological conditions: childhood‐onset epilepsy and recurrent episodes of paroxysmal dystonia and ataxia using the classic 4:1 or <4:1 KD ratios 80‐82 . In a recent serial brain MRI study, 83 patients with PDHC syndrome also demonstrated reversible deep gray matter lesions (basal ganglia) and clinical improvement following the initiation of a KD (here, the reported sum of serum ketones 3‐hydroxybutyrate and acetoacetate was >3 mM). Interestingly, partial or total replacement of KD with ketone bodies (ie, 3‐hydroxybutyrate) was also shown to improve the clinical condition in a small PDHC cohort, indicating that ketone bodies might constitute a potential adjuvant treatment to the KD, 84 which could help to improve KD compliance, diminish side‐effects and improve quality of life.…”

Section: Metabolic Epilepsy Related To Dysfunctional Energy Utilization: Pdhc Deficiencymentioning

confidence: 99%

Metabolic epilepsies amenable to ketogenic therapies: Indications, contraindications, and underlying mechanisms

Gavrilovici

Rho

2020

J of Inher Metab Disea

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Metabolic epilepsies arise in the context of rare inborn errors of metabolism (IEM), notably glucose transporter type 1 deficiency syndrome, succinic semialdehyde dehydrogenase deficiency, pyruvate dehydrogenase complex deficiency, nonketotic hyperglycinemia, and mitochondrial cytopathies. A common feature of these disorders is impaired bioenergetics, which through incompletely defined mechanisms result in a wide spectrum of neurological symptoms, such as epileptic seizures, developmental delay, and movement disorders. The ketogenic diet (KD) has been successfully utilized to treat such conditions to varying degrees. While the mechanisms underlying the clinical efficacy of the KD in IEM remain unclear, it is likely that the proposed heterogeneous targets influenced by the KD work in concert to rectify or ameliorate the downstream negative consequences of genetic mutations affecting key metabolic enzymes and substrates—such as oxidative stress and cell death. These beneficial effects can be broadly grouped into restoration of impaired bioenergetics and synaptic dysfunction, improved redox homeostasis, anti‐inflammatory, and epigenetic activity. Hence, it is conceivable that the KD might prove useful in other metabolic disorders that present with epileptic seizures. At the same time, however, there are notable contraindications to KD use, such as fatty acid oxidation disorders. Clearly, more research is needed to better characterize those metabolic epilepsies that would be amenable to ketogenic therapies, both experimentally and clinically. In the end, the expanded knowledge base will be critical to designing metabolism‐based treatments that can afford greater clinical efficacy and tolerability compared to current KD approaches, and improved long‐term outcomes for patients.

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Prenatal molecular diagnosis of pyruvate dehydrogenase complex deficiency enables rapid initiation of ketogenic diet

Bowen,

Rapalino,

Jaimes

et al. 2024

American J of Med Genetics Pt A

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Pyruvate dehydrogenase complex deficiency (PDCD) is a mitochondrial disorder of carbohydrate oxidation characterized by lactic acidosis and central nervous system involvement. Knowledge of the affected metabolic pathways and clinical observations suggest that early initiation of the ketogenic diet may ameliorate the metabolic and neurologic course of the disease. We present a case in which first trimester ultrasound identified structural brain abnormalities prompting a prenatal molecular diagnosis of PDCD. Ketogenic diet, thiamine, and N‐acetylcysteine were initiated in the perinatal period with good response, including sustained developmental progress. This case highlights the importance of a robust neurometabolic differential diagnosis for prenatally diagnosed structural anomalies and the use of prenatal molecular testing to facilitate rapid, genetically tailored intervention.

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Serial Magnetic Resonance Imaging (MRI) in Pyruvate Dehydrogenase Complex Deficiency

Cited by 10 publications

References 30 publications

Novel imaging findings in pyruvate dehydrogenase complex (PDHc) deficiency—Results from a nationwide population‐based study

Novel imaging findings in pyruvate dehydrogenase complex (PDHc) deficiency—Results from a nationwide population‐based study

Metabolic epilepsies amenable to ketogenic therapies: Indications, contraindications, and underlying mechanisms

Prenatal molecular diagnosis of pyruvate dehydrogenase complex deficiency enables rapid initiation of ketogenic diet

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