M.T. was a full-term male infant (birth weight 2,778 g).

shortly after birth

was lethargic and had difficulty feeding. At two weeks of life, he was found
to be pale, lethargic and hypothermic, with irregular respiration. Blood
lactate was 16mmol/l (normal control <2.4mmol/L ) any pyruvate was 770
umol/L (normal control 34 to 102 umol/L). muscle biopsy did not reveal any
anormality of muscle fiber or mitochondrial architecture. He was treated
with bicarbonate and peritoneal dialysis. His course was complicated by
seizures.
Fibroblasts from skin were cultured and the total pyruvate dehydrogenase
(PDH) activity was measured using (14C-1) pyruvate as a substrate. The
total PDH activity was reduced to < 5% of the activity in a normal control
fibroblast. Further biochemical studies demonstrated that the apparent rate
of degradation of E1(alpha) polypeptide was two to threefold higher in
patient cell line relative to that in normal control fibroblast. After diagnosis
of PDH deficiency by this assay, he was started on a diet with the following
energy distribution: fat 80%, carbohydrate 17% and protein 3%. This was
later changed to 71 to 75% of energy as fat. After starting the ketogenic
diet blood lastate was 4,2 mmoles/L and pyruvate was 360 umol/L. he
continued to have profound developmental delay, hypotonia and
hyperreflexia. He was found dead in bed at age of 13 months. Autopsy
revealed decreased CNS myelination and moderade brain atrophy.

M.T. era un beb varn a trmino (peso al nacer 2778 g). poco despus del
nacimiento era letrgico y tena dificultad para alimentarse. A las dos
semanas de vida, se encontr que era plido, aletargado y con hipotermia,
con la respiracin irregular. Lactato en sangre era 16 mmol / l (control
normal <2,4 mmol / L) cualquier piruvato fue de 770 umol / L (control
normal de 34 a 102 umol / L). biopsia muscular no revel ninguna
anormalidad de la fibra muscular o la arquitectura mitocondrial. Fue tratado
con dilisis con bicarbonato y peritoneal. Su curso se complic por las
convulsiones.
Los fibroblastos de la piel se cultivaron y la actividad total de la
deshidrogenasa de piruvato (PDH) se midi utilizando (1-14C) piruvato
como sustrato. La actividad total de PDH se redujo a <5% de la actividad en
un control normal de fibroblastos. Otros estudios bioqumicos demostraron
que la tasa aparente de la degradacin de E1 (alfa) polipptido era de dos a
tres veces mayor en la lnea celular paciente con respecto a la de
fibroblastos de control normal. Despus del diagnstico de la deficiencia de
PDH en este ensayo, que se inici en una dieta con la siguiente distribucin
de energa: 80% de grasa, 17% de carbohidratos y protenas 3%. Esto fue
cambiado ms adelante a 71 a 75% de la energa en forma de grasa.

Despus de iniciar la dieta cetognica lastate sangre fue 4,2 mmol / L y

piruvato fue 360 mol / L. continu teniendo un profundo retraso en el
desarrollo, hipotona e hiperreflexia. Fue encontrado muerto en la cama a la
edad de 13 meses. La autopsia revel disminucin de la mielinizacin del
SNC y la atrofia cerebral moderada.