?Cerebral? lactic acidosis: defects in pyruvate metabolism with profound brain damage and minimal systemic acidosis

Abstract

Six patients are described with a combination of early onset of neurological symptoms, gross cerebral changes and elevated concentrations of pyruvate and lactate in cerebrospinal fluid. Although at least five of the six patients appear to have a generalised defect in pyruvate metabolism, reflected in deficient pyruvate dehydrogenase activity in cultured fibroblasts, systemic acidosis was not a problem clinically and blood pyruvate and lactate concentrations were only slightly raised. The localisation of significant clinical and biochemical problems to the central nervous system, coupled with the difficulties in making the diagnosis if analysis of cerebrospinal fluid (CSF) is not performed, lead us to term this condition "cerebral" lactic acidosis.

Disorders of mitochondrial function

“…In children with elevated lactate, but otherwise at low clinical risk for mitochondrial disease, we sample on several occasions, if possible before and after meals and through an indwelling catheter, permitting blood sampling at rest and determination of other energy substrates (pyruvate, glucose, amino acids including alanine, ketone bodies). Cerebrospinal fluid (CSF) lactate level is a more reliable diagnostic marker for mitochondrial disease than is blood, especially in patients with brain involvement [23,24]; proton magnetic resonance spectroscopy [25 ] allows noninvasive detection of elevated cerebral lactate and other relevant compounds.…”

Thiamine-Responsive and Non-responsive Patients with PDHC-E1 Deficiency: A Retrospective Assessment

“…Four main neurological presentations have been reported: neonatal encephalopathy with lactic acidosis, non-progressive infantile encephalopathy, Leigh syndrome and relapsing ataxia (Robinson et al 1987;Brown et al 1988Brown et al , 1989aBarnerias et al 2010;Patel et al 2012). The majority of patients have a mutation located in the PDHA1 gene encoding the E1a subunit, which is located on the X chromosome (Robinson and Sherwood 1984;McKay et al 1986;Wicking et al 1986;Brown et al 1989b;Lissens et al 2000).…”

X‐linked pyruvate dehydrogenase E1α subunit deficiency in heterozygous females: Variable manifestation of the same mutation

“…The clinical presentation of this condition is highly variable with the recognized clinical spectrum ranging from severe lactic acidosis in the newborn period to a chronic neurodegenerative disorder with major structural abnormalities in the brain and minimal systemic acidosis (Brown et al 1988;Ho et al 1989;Robinson et at 1989;. Neuropathological findings include both degenerative changes (cerebral atrophy, cystic lesions in the brainstem and basal ganglia) and developmental anomalies (including agenesis of the corpus callosum and absence of the medullary pyramids) (Chow et al 1987).…”