[Clinical features of pyruvate dehydrogenase complex deficiency and gene testing in one case]
Moling Wu1, Li Liu1, Yanna Cai1
1Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center of Guangzhou Medical University, Guangzhou 510623, China.
Insights
Pyruvate dehydrogenase complex deficiency in a child was diagnosed via PDHA1 gene analysis, revealing an R263Q mutation. Early genetic testing and appropriate treatment, including a ketogenic diet, can improve patient outcomes.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Neurology
Background:
- Pyruvate dehydrogenase complex (PDC) deficiency is a rare inherited metabolic disorder.
- It primarily affects the brain, leading to neurological dysfunction.
- Genetic mutations in PDHA1 are a common cause of PDC deficiency.
Observation:
- A 2-year-old boy presented with progressive muscle hypotonia, weakness, and unstable head control.
- Biochemical tests showed persistent hyperlactacidemia with an elevated lactate/pyruvate ratio.
- Brain MRI revealed characteristic bilateral basal ganglia hyperintensities.
Findings:
- Genetic analysis identified a novel G>A point mutation at nucleotide 778 in the PDHA1 gene, resulting in an R263Q substitution.
- This mutation confirmed the diagnosis of pyruvate dehydrogenase complex deficiency.
- The patient's condition stabilized with a ketogenic diet, vitamin B1, coenzyme Q10, and L-carnitine therapy.
Implications:
- This case highlights the variability in clinical presentation and severity of PDC deficiency.
- PDHA1 gene sequencing is crucial for accurate diagnosis in children with unexplained hypotonia and hyperlactacidemia.
- Early diagnosis and targeted treatment can significantly improve the quality of life for affected individuals.
Objective:
To analyze the clinical characteristics and genetype of one children who had been diagnosed with pyruvate dehydrogenase complex deficiency.
Method:
Comprehensive analyses of this case were performed, including clinical symptoms, signs, biochemical examinations and therapeutic effects. The eleven exons and splicing areas of PDHA1 were amplified with genomic DNA from whole blood. And variations were investigated by sequencing the PCR product. The patient was diagnosed with pyruvate dehydrogenase complex deficiency by sequence analysis of PDHA1 gene.
Result:
The patient was a 2 years and 4 monthes old boy. He presented with muscle hypotonia and weakness for one year, and experienced recurrent episodes of unstable head control, unable to sit by himself or stand without support, with persistently hyperlactacidemia. Metabolic testing revealed blood lactate 5.37 mmol/L, pyruvate 0.44 mmol/L, and lactate/pyruvate ratio was 12.23. MRI of the brain showed hyperintense signals on the T2 and T2 Flair weighted images in the basal ganglia bilaterally. Sequence analysis of PDHA1 gene showed a G>A point mutation at nucleotide 778, resulting in a substitution of glutarnine for arginine at position 263 (R263Q). And the diagnosis of pyruvate dehydrogenase complex deficiency was identified. By giving the therapy with ketogenic diet, vitamin B(1), coenzyme Q(10) and L-carnitine , the boy was in a stable condition.
Conclusion:
The severity and the clinical phenotypes of pyruvate dehydrogenase complex deficiency varied. Sequence analysis of PDHA1 gene revealed a 788G>A (R263Q) mutation. Patients who presented with unexplained muscle hypotonia, weakness and hyperlactacidemia could be diveded by gene analysis. And appropriate treatment can improve the quality of life.
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