Congenital lacticacidemia caused by lipoamide dehydrogenase deficiency with favorable outcome,☆☆,

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Abstract

A 5-year-old boy had recurrent vomiting and lethargy with lacticacidemia and ketoacidemia since birth. Lipoamide dehydrogenase deficiency was found in muscle and fibroblasts. Therapy with sodium dichloroacetate, thiamine, and carnitine was associated with reduction of the severity and frequency of the decompensation episodes and near normal plasma lactate levels. At 5 years of age, the patient has normal cognitive function and moderate motor impairment. (J PEDIATR 1995;126:72-4)

Section snippets

CASE REPORT

A 7-month-old boy was admitted because of refusal to eat and recurrent vomiting for 24 hours. He was the third child of nonconsanguineous Ashkenazi-Jewish parents. Two older sisters were healthy. He was born in another hospital after an uneventful pregnancy and delivery; birth weight was 4000 gm. He had an episode of tachypnea and vomiting 12 hours after birth, with a plasma lactate concentration of 7.0 mmol/L (normal, < 2.4 mmol/L) and total ketone bodies of 1.27 mmol/L (normal, < 0.24

METHODS

Plasma lactate levels were determined in 15 samples before therapy was started and in 66 samples during therapy. Urinary organic acids were identified with a Hewlett-Packard 5970 mass selective detector as previously described.6

In muscle homogenate, the activities of rotenone-sensitive NADH:ubiquinone oxidoreductase, antimycine-sensitive succinate:cytochrome c oxidoreductase, cytochrome c oxidase, citrate synthase, PDHC, the E1 subunit, LAD, and α-ketoglutarate dehydrogenase complex were

RESULTS

Mean plasma lactate concentrations were significantly lower after therapy (2.4 ± 0.9 mmol/L) than before (4.8 ± 2.1 mmol/L) (Figure).

On admission, urinary organic acid analysis revealed elevated lactic, β-hydroxybutyric, α-ketoglutaric, and α-ketoadipic acid levels (11.63, 1.47, 4.14, and 0.27 mol/mol creatinine, respectively). After introduction of therapy, only mild organic aciduria was found (0.18, 0.04, 0.94, and 0.15 mol/mol creatinine, respectively).

In muscle, PDHC activity was 0.51 mU/gm

DISCUSSION

Lipoamide dehydrogenase is one of the three catalytic proteins of the PDHC that converts pyruvate to acetyl-coenzyme A. LAD is also a component of two other α-keto acid dehydrogenase complexes: α-ketoglutarate dehy drogenase complex and branched-chain keto acid dehydrogenase complex. Thus a deficiency of LAD results in extensive metabolic disturbances, including lacticacidemia, Krebs cycle dysfunction with decreased NADH production, and impaired degradation of branched-chain amino acids.

Five

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From the Metabolic and Neuropediatric Units, Shaare-Zedek Medical Center, Jerusalem, Israel; the Department of Pediatrics, University Hospital, Nijmegen, The Netherlands; the Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands; the Department of Clinical Biochemistry, Hadassah Medical Center, Jerusalem, Israel; and the Department of Neurology, Columbia Presbyterian Medical Center, New York, New York.

☆☆

Reprint requests: Orly N. Elpeleg, MD, Metabolic Unit, Shaare-Zedek Medical Center, Jerusalem 91031, Israel.

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