Abstract
We present a new case of holocarboxylase synthetase (HCS) deficiency, a rare autosomal recessive metabolic disorder, causing the “early-onset” form of multiple carboxylase deficiency. The patient was born at term of healthy consanguineous parents after an uncomplicated pregnancy. On the 2nd day of life she refused oral feeding, became tachydyspnoeic and showed excessive weight loss. Laboratory studies showed metabolic acidosis, marked lactic acidaemia, hyperammonaemia and increased urinary excretion of 3-hydroxyisovaleric acid, 3-methylcrotonyglycine, 3-hydroxypropionic acid and methylcritric acid. Peritoneal dialysis combined with oral supplementation of biotin (10 mg/day) started on the 3rd day of life resulted in rapid clinical recovery and normalisation of biochemical parameters. HCS deficiency was established in lymphocytes and skin fibroblasts. The activities of all biotin-dependent carboxylases were severely decreased in fibroblasts grown in medium with moderate biotin concentration (10−8 mol/l) but normal in a high biotin medium (10−5 mol/l). Mitochondrial carboxylase activities in lymphocytes were 23%–29% of mean normal during therapy with 20 mg of biotin/day, with the higher dose of 40 mg/day they were within (3-methylcrotoryl-CoA carboxylase, pyruvate carboxylase) or slightly below (propionyl-CoA carboxylase) the normal range. At the age of 3 years the patient's physical and psychomotor development are normal. Early biotin supplementation should be considered in newborns with lactic acidosis and organoaciduria until a final diagnosis has been established. Furthermore, the required individual dose of biotin has to be carefully evaluated biochemically for the individual patient.
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Abbreviations
- ACC:
-
acetyl-CoA carboxylase
- HCS:
-
holocarboxylase synthetase
- 3-HIVA:
-
3-hydroxyisovaleric acid
- MCC:
-
3-methylcrotonyl-CoA carboxylase
- MCD:
-
multiple carboxylase deficiency
- 3-MCG:
-
3-methylcrotonylglycine
- PC:
-
pyruvate carboxylase
- PCC:
-
propionyl-CoA carboxylase
References
Bartlett K, Ghneim HK, Stirk H-J, Wastell H (1985) Enzyme studies in biotin-responsive disorders. J Inherited Metab Dis 8 [Suppl 1]:46–52
Baumgartner ER, Suormala TM, Wick H, Probst A, Blauenstein U, Vest M (1989) Biotinidase deficiency: a cause of subacute necrotizing encephalomyelopathy (leigh syndrome). Report of a case with lethal outcome. Pediatr Res 26:260–266
Briones P, Ribes A, Vilaseca MA (1989) A new case of holocarboxylase synthetase deficiency. J Inherited Metab Dis 12: 329–330
Burri BJ, Sweetman L, Nyhan WL (1985) Heterogeneity of holocarboxylase synthetase in patients with biotin-responsive multiple carboxylase deficiency. Am J Hum Genet 37:326–337
Duran M, Bruinvis L, Ketting D, Klerk JBC de, Wadman SK (1988) Cis-4-Decenoic acid in plasma: a characteristic metabolite in medium-chain acyl-CoA dehydrogenase deficiency. Clin Chem 34:548–551
Frigg M, Brubacher G (1976) Biotin deficiency in chicks fed a wheat-based diet. Int J Vitam Nutr Res 46:314–321
Leighton F, Poole B, Beaufay H (1968). The large-scale separation of peroxisomes, mitochondria and lysosomes from the liver of rats injected with Triton WR-1339. J Cell Biol 37:482–513
Michalski AJ, Berry GT, Segal S (1989) Holocarboxylase synthetase deficiency: 9-year follow-up of a patient on chronic biotin therapy and a review of the literature. J Inherited Metab Dis 12:312–316
Sherwood WG, Saunders M, Robinson BH, Brewster T, Gravel RA (1982) Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset. J Pediatr 101:546–550
Suormala T, Wick H, Bonjour J-P, Baumgartner ER (1985) Rapid differential diagnosis of carboxylase deficiency and evaluation of biotin-responsiveness in a single blood sample. Clin Chim Acta 145:151–162
Wolf B, Heard GS (1989) Disorders of biotin metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 2083–2103
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Fuchshuber, A., Suormala, T., Roth, B. et al. Holocarboxylase synthetase deficiency: Early diagnosis and management of a new case. Eur J Pediatr 152, 446–449 (1993). https://doi.org/10.1007/BF01955908
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DOI: https://doi.org/10.1007/BF01955908