Pyruvate dehydrogenase-E1α deficiency presenting as recurrent acute proximal muscle weakness of upper and lower extremities in an 8-year-old boy

Kara, Bülent; Genç, Hülya Maraş; Uyur-Yalçın, Emek; Sakarya-Güneş, Ayfer; Topçu, Uğur; Mülayim, Serap; Ceylaner, Serdar

doi:10.1016/j.nmd.2016.11.001

Cited by 11 publications

(7 citation statements)

References 9 publications

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“…The catalytic domains consist of E1, is a heterotetramer of two alpha and two beta subunits, E2 and E3 domains [2]. The structural domain is identified as the E3-binding protein [3, 4]. Thus, in PDCD, decrease in the availability of acetyl CoA reduces the production of cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide, whose primary function is to provide the respiratory chain with electrons for oxidative phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Pyruvate Dehydrogenase Complex Deficiency: An Unusual Cause of Recurrent Lactic Acidosis in a Paediatric Critical Care Unit

Gupta

Rutledge

2018

The Journal of Critical Care Medicine

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Pyruvate dehydrogenase complex deficiency (PDCD) is a rare neurodegenerative disorder associated with abnormal mitochondrial metabolism. Structural brain abnormalities are common in PDCD. A case of a patient with PDCD with an unusual presentation is described. A 20-month-old boy with hypotonia and developmental delay, presented with hypoxia and respiratory distress due to bronchiolitis. During hospitalisation, he was prescribed PediaSure® feeds. Two days after starting these feeds, he developed respiratory arrest requiring intubation. His blood gas before arrest revealed lactate of 8.9 mmol/L despite normal haemodynamics. After stabilisation and a period of compulsory fasting, subsequent feeding with PediaSure® resulted in the recurrence of lactic acidosis. A metabolic workup revealed an elevated serum pyruvate level. Brain MRI was normal. Skeletal muscle biopsy confirmed PDCD. The most common cause of PDCD is a mutation in the X-linked PDHA1 gene. The severity of PDCD can range from neonatal death to more delayed onset of symptoms as in our index case. Normal brain MRI is reported in only 2% of patients with PDCD. There is no effective treatment for PDCD. In patients with proximal muscle weakness and feeding intolerance with glucose-containing feeds, the presence of lactic acidosis should raise the suspicion of PDCD irrespective of the patient's age and normal MRI.

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Section: Discussionmentioning

confidence: 99%

Pyruvate Dehydrogenase Complex Deficiency: An Unusual Cause of Recurrent Lactic Acidosis in a Paediatric Critical Care Unit

Gupta

Rutledge

2018

The Journal of Critical Care Medicine

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“…Kara et al describes a case of PDHA1 deficiency in a 8 year old boy who presented with acute proximal weakness after respiratory infection and MRI showed symmetrical bilateral globus pallidal hyperintensities [3]. Another mutation at same codon was reported by Naito et al [7] in a patient with PDHC deficiency and West syndrome.…”

Section: Discussionmentioning

confidence: 94%

“…Slowly progressive Leigh syndrome in girls and ataxia in males are the least severe clinical phenotypes of PDHC [2]. Rarely, paroxysmal neurologic problems such as intermittent ataxia, episodic weakness, exerciseinduced dystonia, and recurrent demyelination may be seen [3,4].…”

Section: Discussionmentioning

confidence: 99%

Pyruvate Dehydrogenase Deficiency with Cerebral Vasculitis

Joseph¹

2020

AJBSR

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gastrointestinal illness. Exam was notable for flaccid quadriparesis, hyporeflexia without encephalopathy. He received IVIG for presumed Guillain Barre syndrome. Initial CSF analysis and MRI Brain/spine were unremarkable except high CSF lactate of 2.9. A week later, he became less responsive, had autonomic fluctuations, lost gag reflex, and got intubated. Repeat MRI Brain showed new bilateral (L>R) cortical, subcortical and brainstem lesions as seen in Figures 1A, 1B & 1C. Serial MRI brain showed fast developing multiple lesions involving the white and gray brain matter with areas of restricted diffusion. Repeat CSF analysis including encephalopathy/ multiple sclerosis panel were unremarkable. Biopsy of left frontal lesion showed vasculitis with lymphocytic infiltration and areas of small hemorrhage with no necrosis as shown in Figures 2A & 2B. He had no response to 7 days of IV steroids or IVIG. Cyclophosphamide therapy was started for presumed CNS vasculitis and mitochondrial cocktail for high serum/CSF lactate though rest of the mitochondrial labs returned negative. Infectious work up for Aspergillus, hepatitis B&C, Bartonellosis, Lyme, Tuberculosis and HIV were negative.

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“…3,4 To date, few documented cases have reported an isolated peripheral neuropathy mimicking either a Guillain-Barre syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) as predominant clinical presentation. 3,[5][6][7][8][9][10][11] Here, we report a case with PDH deficiency related to a PDHA1 mutation, presenting at the onset with episodic weakness and neurophysiological features resembling CIDP.…”

Section: Introductionmentioning

confidence: 93%

“…To date, few documented cases have reported an isolated peripheral neuropathy mimicking either a Guillain-Barre syndrome (GBS) or Chronic Inflammatory Polyneuropathy (CIDP) as predominant clinical presentation 3,[5][6][7][8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Recurrent Sensory-Motor Neuropathy Mimicking CIDP as Predominant Presentation of PDH Deficiency

et al. 2023

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Introduction: PDH deficiency (OMIM # 312170) is a relatively common mitochondrial disorder, caused by mutations in the X-linked PDHA1 gene and presenting with a variable phenotypic spectrum, ranging from severe infantile encephalopathy to milder chronic neurological disorders. Isolated peripheral neuropathy as predominant clinical presentation is uncommon. Results: We report on a patient, now 21 years old, presenting at the age of 2 years with recurrent symmetric weakness as first symptom of a PDH deficiency. Neurophysiological evaluation proving a sensory-motor polyneuropathy with conduction blocks and presence of elevated CSF proteins, suggested a chronic inflammatory polyneuropathy (CIDP). The evidence of high serum lactate and the alterations in oxidative metabolism in muscle biopsy pointed toward the final diagnosis. After starting nutritional supplements, no further episodes occurred. A hemizygous mutation in PDHA1 (p.Arg88Cys) was identified. This mutation has been previously described in 5 patients with a similar phenotype. A 3D-reconstruction demonstrated that mutations affecting this Arg88 destabilize the interactions between the subunits of the E1 complex. Conclusion: We summarize the clinical and genetic characteristics of one patient with PDH deficiency presenting isolated peripheral nervous system involvement. This study highlights that the diagnosis of PDH deficiency should be considered in children with unexplained peripheral neuropathy, even with features suggestive of acquired forms, especially in case of early onset and limited response to treatment. A simple analysis of lactic acid could help to target the diagnosis. In addition, we suggest that the residue Arg88 is the most frequently involved in this specific phenotype of PDH deficiency.

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Pyruvate dehydrogenase-E1α deficiency presenting as recurrent acute proximal muscle weakness of upper and lower extremities in an 8-year-old boy

Cited by 11 publications

References 9 publications

Pyruvate Dehydrogenase Complex Deficiency: An Unusual Cause of Recurrent Lactic Acidosis in a Paediatric Critical Care Unit

Pyruvate Dehydrogenase Complex Deficiency: An Unusual Cause of Recurrent Lactic Acidosis in a Paediatric Critical Care Unit

Pyruvate Dehydrogenase Deficiency with Cerebral Vasculitis

Recurrent Sensory-Motor Neuropathy Mimicking CIDP as Predominant Presentation of PDH Deficiency

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