Congenital lacticacidemia caused by lipoamide dehydrogenase deficiency with favorable outcome☆,☆☆,★
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
References (11)
- et al.
Familial benign hypotonia of childhood due to isolated 3-methylcrotonyl-CoA carboxylase deficiency
J PEDIATR
(1992) - et al.
Studies on the mechanism of activation of adipose tissue pyruvate dehydrogenase by insulin
J Biol Chem
(1973) The pharmacology of dichloroacetate
Metabolism
(1989)- et al.
Lipoamide dehydrogenase deficiency with primary lactic acidosis: favorable response to treatment with oral lipoic acid
J PEDIATR
(1983) - et al.
Congenital lactic acidosis, α-ketoglutaric aciduria and variant form of maple syrup urine disease due to a single enzyme defect: dihydrolipoyl dehydrogenase deficiency
Acta Paediatr Scand
(1982)
Cited by (36)
The phenotypic spectrum of dihydrolipoamide dehydrogenase deficiency in Saudi Arabia
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2018, Volpe's Neurology of the NewbornDisorders of pyruvate metabolism
2013, Handbook of Clinical NeurologyCitation Excerpt :Progressively, hypotonia, psychomotor retardation, microcephaly, and spasticity occur. Some patients develop a typical picture of Leigh encephalopathy (Elpeleg et al., 1995, 1997; Grafakou et al., 2003; Hong et al., 2003). A clinical Reye-like picture with liver involvement and myopathy with myoglobinuria without mental retardation has been seen in Ashkenazi Jewish patients with an E3 deficiency (Shaag et al., 1999).
The spectrum of pyruvate dehydrogenase complex deficiency: Clinical, biochemical and genetic features in 371 patients
2012, Molecular Genetics and MetabolismCitation Excerpt :We sought associations among various pathological indices that could provide new insight into the pathobiology and clinical course of this disease. We reviewed all English language publications under “pyruvate dehydrogenase deficiency” and deficiency of each individual subunit and component of the complex listed in PubMed and Google Scholar from 1970 through December, 2010 [6,10–163]. Additional publications were found by reviewing the references included in articles not identified by the search engines.
Thiamine and Parkinson's disease
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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.
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Reprint requests: Orly N. Elpeleg, MD, Metabolic Unit, Shaare-Zedek Medical Center, Jerusalem 91031, Israel.
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0022-3476/95/$3.00 + 09/22/60180