Pyruvate dehydrogenase phosphatase deficiency: a cause of congenital chronic lactic acidosis in infancy.

Abstract:

:A male child presented on the first day of life with metabolic acidosis with elevated blood lactate (15 mM), pyruvate (0.4 mM), and free fatty acid (1.3 mM) levels and a blood pH of 7.16. The severity of the acidosis was diminished by intravenous administration of glucose in large doses and by bicarbonate. On two occasions, when the acidosis was particularly severe, peritoneal dialysis using an acetate buffer was required. Restriction of the dietary intake of saturated fatty acids or treatment with nicotinic acid also appeared to diminish the severity of acidosis. No improvement was achieved by the administration of thiamine or biotin. Tissues taken at postmortem showed normal activity of gluconeogenic enzymes and pyruvate dehydrogenase. The activity of pyruvate dehydrogenase in tissue homogenates preincubated with ATP was reduced by 60-75% both in liver of the patient and of the controls because of the inactivation of the enzyme by pyruvate dehydrogenase kinase. Addition of Ca++ and Mg++ to the inactivated enzyme caused a prompt return of the activity to normal in controls but not in the patient. This defect, which was apparent in muscle and liver but not in brain, we attribute to a markedly reduced activity of pyruvate dehydrogenase phosphatase in the patient.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Robinson BH,Sherwood WG

doi

10.1203/00006450-197512000-00015

subject

Has Abstract

pub_date

1975-12-01 00:00:00

pages

935-9

issue

12

eissn

0031-3998

issn

1530-0447

journal_volume

9

pub_type

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