Peak Performance: Magnetic Resonance Spectroscopy in the Diagnosis of Pyruvate Dehydrogenase Complex Deficiency

A bstract A 10-month-old male with congenital hypotonia and failure to thrive was admitted owing to fever, lethargy, and progressive hypotonia following an influenza B infection. Brain magnetic resonance imaging (MRI) demonstrated T2 prolongation in the putamen and globus pallidus, reduced diffusivity in the globus pallidus, and parenchymal volume loss, concerning for a mitochondrial disorder with a Leigh-like phenotype, given the temporally disparate lesions in the lentiform nucleus. Proton magnetic resonance spectroscopy (H1-MRS) revealed elevated pyruvate (2.37 ppm), lactate (1.33 ppm), and alanine (1.48 ppm), forming a highly characteristic metabolic profile of pyruvate dehydrogenase complex deficiency (PDCD). Follow-up cerebrospinal fluid and plasma analysis corroborated these findings, demonstrating proportionally elevated lactate, pyruvate, alanine, and proline levels. A pathogenic variant in PDHA1 confirmed the diagnosis. PDCD is a rare mitochondrial disorder caused by defective pyruvate metabolism and impaired aerobic energy production. While genetic testing remains the diagnostic gold standard, early recognition of imaging patterns can expedite diagnosis and clinical management, particularly during periods of metabolic decompensation. This case illustrates the benefit of combining MRI and H1-MRS in the evaluation of suspected mitochondrial encephalopathy. While MRI findings such as temporally disparate basal ganglia lesions and cerebral volume loss may suggest mitochondrial disease, the addition of H1-MRS provides key metabolic information that increases diagnostic confidence. In our case, the concurrent elevation in pyruvate, lactate, and alanine levels is highly suggestive of PDCD and prompted confirmatory genetic testing. H1-MRS is a powerful adjunct to conventional MRI, enhancing the diagnostic accuracy of neuroimaging in mitochondrial disorders such as PDCD and enabling earlier, targeted intervention.