Pyruvate dehydrogenase deficiency: clinical and biochemical diagnosis.
A female neonate with pyruvate dehydrogenase (PDH) deficiency is presented with clinical, radiologic, biochemical, neuropathologic, and molecular genetic data. She was dysmorphic, with a high forehead, lowset ears, thin upper lip, upturned nose, and rhizomelic limbs. Cranial MRI revealed severe cortical atrophy, ventricular dilatation, and corpus callosum agenesis. Pyruvate and lactate levels were increased in CSF and blood. Urinary organic acid profile was compatible with PDH deficiency. PDH activity was normal in fibroblasts, lymphocytes, and muscle. The PDH E1-alpha gene was sequenced and a single base mutation was found within the regulatory phosphorylation site in exon 10. It is postulated that this mutation causes a cerebral form of PDH deficiency. Tissue-specific expression of the disease could be explained by differential X chromosome inactivation because the PDH E1-alpha gene is located on this chromosome. Dysmorphism with severe cerebral malformations in female patients merits a metabolic evaluation, including determination of lactate and pyruvate levels in CSF.
De Meirleir
L
L
Department of Pediatrics, Academic Hospital, Free University Brussels, Belgium.
Lissens
W
W
Denis
R
R
Wayenberg
J L
JL
Michotte
A
A
Brucher
J M
JM
Vamos
E
E
Gerlo
E
E
Liebaers
I
I
D001921:Brain / Q000002:abnormalities* / Q000201:enzymology / Q000473:pathology; D002874:Chromosome Mapping; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007773:Lactates / Q000134:cerebrospinal fluid; D019344:Lactic Acid; D008099:Liver / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008830:Microbodies / Q000648:ultrastructure; D008854:Microscopy, Electron; D009132:Muscles / Q000473:pathology; D009460:Neurologic Examination; D030481:Pyruvate Dehydrogenase (Lipoamide); D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011773:Pyruvates / Q000134:cerebrospinal fluid; D019289:Pyruvic Acid
D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D019344:Lactic Acid; D019289:Pyruvic Acid; D030481:Pyruvate Dehydrogenase (Lipoamide)