The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.
BACKGROUND
Pyruvate dehydrogenase complex (PDC) deficiency is a genetic mitochondrial disorder commonly associated with lactic acidosis, progressive neurological and neuromuscular degeneration and, usually, death during childhood. There has been no recent comprehensive analysis of the natural history and clinical course of this disease.


OBJECTIVE
We reviewed 371 cases of PDC deficiency, published between 1970 and 2010, that involved defects in subunits E1α and E1β and components E1, E2, E3 and the E3 binding protein of the complex.


METHODS
English language peer-reviewed publications were identified, primarily by using PubMed and Google Scholar search engines.


RESULTS
Neurodevelopmental delay and hypotonia were the commonest clinical signs of PDC deficiency. Structural brain abnormalities frequently included ventriculomegaly, dysgenesis of the corpus callosum and neuroimaging findings typical of Leigh syndrome. Neither gender nor any clinical or neuroimaging feature differentiated the various biochemical etiologies of the disease. Patients who died were younger, presented clinically earlier and had higher blood lactate levels and lower residual enzyme activities than subjects who were still alive at the time of reporting. Survival bore no relationship to the underlying biochemical or genetic abnormality or to gender.


CONCLUSIONS
Although the clinical spectrum of PDC deficiency is broad, the dominant clinical phenotype includes presentation during the first year of life; neurological and neuromuscular degeneration; structural lesions revealed by neuroimaging; lactic acidosis and a blood lactate:pyruvate ratio ≤ 20.
Department of Medicine (Division of Endocrinology, Metabolism and Diabetes), College of Medicine, University of Florida, Gainesville, FL 32611, USA.
Kavi P
KP
Patel
Thomas W
TW
O'Brien
Sankarasubramon H
SH
Subramony
Jonathan
J
Shuster
Peter W
PW
Stacpoole
D005260:Female; D006801:Humans; D008297:Male; D039781:PubMed; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics / Q000378:metabolism; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D011768:Pyruvate Dehydrogenase Complex