Pyruvate Dehydrogenase-E1α Deficiency Presenting as Recurrent Demyelination: An Unusual Presentation and a Novel Mutation

Abstract

The nucleus-encoded mitochondrial pyruvate dehydrogenase enzyme complex plays key roles in cellular energy metabolism and acid-base equilibrium. Pyruvate dehydrogenase complex deficiency is due to loss-of-function mutation in one of the five component enzymes, most commonly E1α-subunit. The common clinical presentation ranges from fatal infantile lactic acidosis in newborns to chronic neurological dysfunction. We describe here an unusual presentation of E1α-subunit deficiency presenting as recurrent demyelination, Guillain-Barré syndrome-like demyelinating polyneuropathy at the onset, and ophthalmoplegia in a young infant. The clinical phenotype of the mutation in the patient was unique as compared to the previous reported cases of pyruvate dehydrogenase deficiency. The mother was found to be a mosaic carrier of the mutation. This phenotypic variability of pyruvate dehydrogenase complex deficiency and early suspicion of its unusual neurological manifestations is highlighted. Thiamine and ketogenic diet can be helpful.

Genome sequence variation in two subspecies of western honeybee, A.m.carnica and A.m.ligustica

“…Since the activity of the E1 component affects the activity of whole PDH complex, the different genetic variants of the E1 component may play a role in adaptive traits related to energy metabolism. In some cases the deficiency of E1 subunit can cause the demyelination, resulting in neurological symptoms (Singhi et al, 2013).…”

Quantitative Proteomic and Network Analysis of Differentially Expressed Proteins in PBMC of Friedreich’s Ataxia (FRDA) Patients

“…Protein interacting with C kinase (PICK1) was included in the network by default (STRING) due to its interaction with one of the query proteins, MYL12A. A strong interaction observed between PDHE1 and FXN in the PPI network indicates the role of PDHE1 in connection with the reported brain anomalies like cerebral cortex atrophy and demyelination (Singhi et al, 2013), weak muscle tone and poor coordination (Debray et al, 2008), and cardiac complications (Gopal et al, 2018) in FRDA patients. The other interactions among ACTC1, ACTN1, MYL12A, and SORBS1 further suggest their correlation in several cellular pathways like insulin signaling and cross bridge cycling kinetics of skeletal and cardiac muscles, which are indeed compromised in FRDA (Figure 4).…”

The Role of Thiamine in Wilson′s Disease: Possible Genetic and Cellular Signaling Mechanisms

“…Thiamine deficiency reduces the activity of the thiamine dependent-enzymes KGDHC and PDH and also induces regional selective neurodegeneration [17][18][19]. Thiamine and TPP have been used in patients with PDH deficiency [20][21][22][23][24] and KGDH deficiency diseases [25][26][27]. Taken together, these findings suggest that there is a relationship between thiamine and Wilson's disease.…”