Abstract
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 involvement of globus pallidus were present in 12, while leukoencephalopathy was present in 6 and stroke-like lesions in 3 individuals. A combination of prenatal developmental and clastic lesions was present in 15 individuals. In addition, one male with PDHA1 also had postnatal clastic lesions. The most common lesions found in our study were agenesis or hypoplasia of corpus callosum, ventriculomegaly, or Leigh-like lesions. Furthermore, we describe a broad spectrum of other MRI changes that include leukoencephalopathy and stroke-like lesions. We argue that a novel important clue, suggesting the possibility of PDHc deficiency on MRI scans, is the simultaneous presence of multiple lesions on MRI that have occurred during different phases of brain development.
Highlights
The pyruvate dehydrogenase complex (PDHc) is a multienzyme complex in the mitochondria that converts pyruvate, the end product of glycolysis to acetyl-CoA which in turn enters the Krebs cycle, and enables aerobic energy production.[1]
We argue that a novel important clue, suggesting the possibility of PDHc deficiency on MRI scans, is the simultaneous presence of multiple lesions on MRI that have occurred during different phases of brain development
An important clue from our study that should suggest the possibility of PDHc deficiency is the simultaneous presence of multiple lesions on MRI that have occurred during different phases of brain development
Summary
The pyruvate dehydrogenase complex (PDHc) is a multienzyme complex in the mitochondria that converts pyruvate, the end product of glycolysis to acetyl-CoA which in turn enters the Krebs cycle, and enables aerobic energy production.[1]. PDHc deficiency has a large phenotypical variation ranging from neonatal encephalopathy with lactic acidosis to nonprogressive infantile encephalopathy, Leigh syndrome, and relapsing ataxia.[6] The brain lesions have been attributed to two main mechanisms: (a) low energy supply during embryonic development resulting in agenesis or hypoplasia of the corpus callosum or abnormalities of cortical gyration and (b) acute energy failure either prenatally resulting in ventriculomegaly and periventricular cysts or postnatally causing acute basal ganglia or brainstem lesions.[6,10]. Prompt diagnosis is important to enable early initiation of treatment The aim of this nationwide population-based study was to delineate the neuroradiological spectrum of PDHc deficiency and its evolvement over time
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