Recurrent Hypoglycemia Associated with Glutaric Aciduria Type II in an Adult

Dusheiko, Geoffrey; Kew, Michael C.; Joffe, B. I.; Lewin, Jack R.; Path, F. F.; Mantagos, Stefanos; Tanaka, Kay

doi:10.1056/nejm197912273012601

Cited by 112 publications

(43 citation statements)

References 24 publications

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“…There is a wide spectrum of clinical phenotypes, ranging from pre-and neonatal, rapidly fatal, forms (1) to later-onset forms manifesting from juvenile to adult age (2)(3)(4)(5). It may be severe or even fatal at any age (6,7).…”

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confidence: 99%

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Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency–related leukodystrophy

et al. 2014

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Background: Multiple acyl-CoA dehydrogenase deficiency-(MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein-and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once. Methods:We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging. results: During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay. conclusion: NaHB is a highly effective and safe treatment that needs further controlled studies.

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“…Clinical manifestations include hypoketotic hypoglycaemia, metabolic acidosis, cardiomyopathy, neurodevelopmental delay with leukodystrophy and myopathy. Their expression and severity may vary within the same family (2).…”

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Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency–related leukodystrophy

et al. 2014

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“…Leucine metabolism is also blocked at the level of isovaleryl-CoA dehydrogenation in another inborn metabolic disorder, glutaric aciduria type II (GA II) (12)(13)(14)(15). Like IVA, this disease is characterized by the excretion of large amounts of isovaleric acid, but unlike patients with IVA, several other short-chain fatty acids and dicarboxylic acids including glutaric, adipic, ethylmalonic, isobutyric, and 2-methylbutyric acids are excreted as well (12,13,15).…”

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confidence: 99%

“…Like IVA, this disease is characterized by the excretion of large amounts of isovaleric acid, but unlike patients with IVA, several other short-chain fatty acids and dicarboxylic acids including glutaric, adipic, ethylmalonic, isobutyric, and 2-methylbutyric acids are excreted as well (12,13,15). Thus, the defect in GA II comprises a wide range of metabolic reactions in which several different short-chain acyl-CoA, including isovaleryl-CoA, are dehydrogenated.…”

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confidence: 99%

Complementation studies of isovaleric acidemia and glutaric aciduria type II using cultured skin fibroblasts.

Dubiel¹,

Dabrowski²,

Wetts³

et al. 1983

J. Clin. Invest.

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“…Both ETF and ETF-QO deficiency result in inhibition of several metabolic pathways (fatty acids, lysine, and branchedchain amino acids) at the respective acyl-CoA dehydrogenase step and induce intermittent urinary excretion of dicarboxylic acids (1,(3)(4)(5) and acylconjugates (4)(5)(6)(7)(8)(9). Although the pattern of organic acid excretion is highly variable, either glutaric acid or ethylmalonic acid and adipic acid are the major components when a diagnostic profile is detected in a given urine sample.…”

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Ethylmalonic/Adipic Aciduria: Effects of Oral Medium-Chain Triglycerides, Carnitine, and Glycine on Urinary Excretion of Organic Acids, Acylcarnitines, and Acylglycines

et al. 1991

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ABSTRACT. A 9-y-old girl with ethylmalonic/adipic aciduria was hospitalized to determine the possible therapeutic efficacy of oral carnitine and glycine supplementation. To provoke a mild metabolic stress, her diet was supplemented with 440 mg/kg/d of medium-chain triglycerides. She was treated successively with carnitine (100 mg/kg/d) for 5 d, neither carnitine nor glycine for 2 d, and then glycine (250 mglkgld) for 6 d. Consecutive 12-h urine collections were obtained throughout the entire period. The urinary excretion of eight organic acids, four acylglycines, and four acylcarnitines, which accumulate as a result of a metabolic block of five mitochondrial acyl-CoA dehydrogenases, were quantitatively determined by capillary gas chromatography, stable isotope dilution gas chromatographylmass spectrometry, and radioisotopic exchange HPLC, respectively. The excretion of each group of metabolites was calculated as the mean percentage of total output (pmo1124 h) during the four phases of the protocol (organic acids/acylglycines/acylcarnitines = 100.0%): 1) regular diet (3 d); 88.1110.811.1; 2) medium-chain triglyceride supplementation (4); 82.5115.611.9; 3) medium-chain triglycerides plus carnitine (5); 79.218.2112.6; and 4) medium-chain triglycerides plus glycine (6); 81.0/18.7/0.3. Comparison between total and individual excretion of acylglycines and acylcarnitines indicates that oral glycine supplementation enhanced the conjugation and excretion of fatty acyl-CoA intermediates as efficiently as carnitine. We propose that oral glycine supplementation should be considered in the treatment of other inborn errors of metabolism associated with abnormal urinary excretion of acylglycines. (Pediatr Res 30: 216-221, 1991) Abbreviations AC, acylcarnitines AG, acylglycines BC, butyrylcarnitine BG, butyrylglycine ETF, electron transfer flavoprotein ETF-QO, ETF-ubiquinone oxidoreductase HC, hexanoylcarnitine HG, hexanoylglycine

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Recurrent Hypoglycemia Associated with Glutaric Aciduria Type II in an Adult

Cited by 112 publications

References 24 publications

Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency–related leukodystrophy

Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency–related leukodystrophy

Complementation studies of isovaleric acidemia and glutaric aciduria type II using cultured skin fibroblasts.

Ethylmalonic/Adipic Aciduria: Effects of Oral Medium-Chain Triglycerides, Carnitine, and Glycine on Urinary Excretion of Organic Acids, Acylcarnitines, and Acylglycines

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