Abstract
We report the first case of isolated biotin resistant 3-methylcrotonyl-CoA carboxylase (MCC) deficiency in Argentina. The diagnosis was established at 14 months of age by urinary organic-acid analysis and confirmed by enzyme assay in fibroblasts. The patient suffered from severe psychomotor retardation, hypotonia, areflexia, and failure to thrive, and died unexpectedly at 3 years 4 months of life. Brain MRI at 14 months showed signals of the white matter on cerebral T2-weighted, which were indicative of confluent and multiple foci of leukodystrophy, a pattern not previously described in this entity. In addition, high levels of oxypurines were detected in cerebrospinal fluid. This might be related to energetic consequences of the enzyme deficiency in the brain. This case extends the phenotype of isolated MCC deficiency in infancy and suggests this entity should be considered to be one of the possible causes of “metabolic leukodystrophies.”
Similar content being viewed by others
REFERENCES
Bannwart, C., Wermuth B., Baumgartner, R., Suormala, T., and Wiesmann, U.N. (1992). Isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency presenting as a clinically severe form in a newborn with fatal outcome. J. Inherit. Metab. Dis. 15:863-868.
Barcovich, A.J. and Lindan, C.E. (1994). Congenital cytomegalovirus infection of the brain: Imaging analysis and embriologic considerations. Am. J. Neuroradiol. 15:703-717.
de Kremer, R., Depetris-Boldini, C., Kelley, R.I., and Civallero, G.E. (1997). Deficiencia de la 2-metilacetoacetil-CoA tiolasa mitocondrial en Argentina. Medicina 57:52-58.
Dove Pettit, D.A. and Wolf, B. (1991). Quantitive colorimetric assay of biotinidase activity. In (F.A. Hommes, ed.), Techniques in Diagnostic Human Biochemical Genetics. A Laboratory Manual, Wiley-Liss, pp. 561-565.
Duran, M., Baumgartner, E.R., Suormala, T.M., Bruinvis, L., Dorland, L., Smeitink, J.A., and Poll-The, B.T. (1993). Cerebrospinal fluid organic acids in biotinidase deficiency. J. Inherit. Metab. Dis. 16:513-516.
Elpeleg, O.N., Havkin, S., Barash, V., Jakobs, C., Glick, B., and Shalev, R.S. (1992). Familial hypotonia of childhood caused by isolated 3-methylcrotonyl-CoA carboxylase deficiency. J. Pediatr. 121:407-410.
Gibson, K.M., Naylor, E.W., and Morton, D.H. (1996). 3-Methylcrotonyl-Coenzyme A carboxylase (MCC) deficiency in adult Amish/Mennonites identified by detection of incresed acylcarnitines in blood spots of their offspring. J. Inherit. Metab. Dis. 19(Suppl. 1):47, P94.
Hoffmann, G.F., Meier-Augenstein,W., Stöckler, S., Surtees, R., Rating, D., and Nyhan,W.L. (1993). Physiology and pathophysiology of organic acids in cerebrospinal fluid. J. Inherit. Metab. Dis. 16:648-669.
Kobori, J.A., Johnston, K., Sweetman, L., Schmidt, K., Jurecki, E., Wolf, B., Goodman, S., and Packman, S. (1989). Isolated 3-methylcrotonyl-CoA carboxylase deficiency presenting as a reye-like syndrome. Ped. Res. 25:142A.
Lehnert,W., Niederhoff, H., Suormala, T., and Baumgartner, E.R. (1996). Isolated biotin-resistant 3-metylcrotonyl-CoA carboxylase deficiency. Long-term outcome in a case with neonatal onset. Eur. J. Pediatr. 155:568-572.
Moser, H.W. and Moser, A.B. (1991a). Measurement of phytanic acid levels. In (F.A. Hommes, ed.), Techniques in Diagnostic Human Biochemical Genetics. A Laboratory Manual, Wiley-Liss, pp. 193-203.
Moser, H.W. and Moser, A.B. (1991b). Measurement of saturated very long chain fatty acids in plasma. In (F.A. Hommes, ed.), Techniques in Diagnostic Human Biochemical Genetics. A Laboratory Manual, Wiley-Liss, pp. 177-191.
Mourmans, J., Bakkeren, J., de Jong, J., Wevers, R., van Diggelen, O.P., Suormala, T., Baumgartner, R., and Wendel, U. (1995). Isolated (biotin-resistant) 3-methylcrotonyl-CoA carboxylase deficiency: Four sibs devoid of pathology.J. Inherit. Metab. Dis. 18:643-645.
Murayama, K., Kimura, M., Yamaguchi, S., Shinka, T., and Kodama, K. (1997). Isolated 3-methylcrotonyl-CoA carboxylase deficiency in a 15-year-old girl. Brain Develop. 19:303-305.
Rutledge, S.L., Berry, G.T., Stanley, C.A., van Hove, J.L.K., and Millington, D. (1995). Glycine and L-carnitine therapy in 3-methylcrotonyl-CoA carboxylase deficiency. J. Inherit. Metab. Dis. 18:299-305.
Schmidt, H., Siems, W.G., Grune, T., and Grauel, E.L. (1995). Concentration of purine compound in the cerebrospinal fluid of infants suffering from sepsis, convulsions and hydrocephalus. J. Perinat. Med. 23: 167-174.
Simmonds, H.A., Duley, J.A., and Davies, P.M. (1991). Analysis of purines and pyrimidines in blood, urine, and other physiological fluids. In (F.A. Hommes, ed.), Techniques in Diagnostic Human Biochemical Genetics. A Laboratory Manual, Wiley-Liss, pp. 397-424.
Steen, C., Baumgartner, E.R., Duran, M., Lehnert,W., Suormala, T., Fingerhut, S.R., Stehn, M., and Kohlschütter, A. (1999). Metabolic stroke in isolated 3-methylcrotonyl-CoA carboxylase deficiency. Eur. J. Pediatr. 158:730-733.
Stover, J.F., Lowitzsch, K., and Kempski, O.S. (1997). Cerebrospinal fluid hypoxanthine, xanthine and uric acid levels may reflect glutamate-mediated excitotoxicity in different neurological diseases. Neurosci. Lett. 238:25-28.
Suormala, T., Packman, S., Whitney, S., Fowler, B., and Baumgartner, E.R. (1997). Isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency: Genetic complementation and assignment of the defect to the ?-or ?-chain of the MCC. J. Inherit. Metab. Dis. 20(Suppl. 1):34, P3.9.
Suormala, T., Wick, H., Bonjour, J.P., and Baumgartner, E.R. (1985). Rapid differential diagnosis of carboxylase deficiencies and evaluation of biotin responsiveness in a single blood sample. Clin. Chim. Acta 145:151-162.
Sweetman, L., and Williams, J.C. (1995). Branched chain organic acidurias. In (C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle, eds.), The Metabolic and Molecular Bases of Inherited Diseases, McGraw-Hill, New York, pp. 1387-1422.
Wenger, D.A. and Williams, C. (1991). Screening for lysosomal disorders. In (F.A. Hommes, ed.), Techniques in Diagnostic Human Biochemical Genetics. A Laboratory Manual, Wiley-Liss, pp. 587-617.
Wiesmann, U.N., Suormala, T., Pfenninger, J., and Baumgartner, E.R. (1998). Partial 3-methylcrotonyl-CoA carboxylase deficiency in an infant with fatal outcome due to progressive respiratory failure. Eur. J. Pediatr. 157:225-229.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
de Kremer, R.D., Latini, A., Suormala, T. et al. Leukodystrophy and CSF Purine Abnormalities Associated with Isolated 3-Methylcrotonyl-CoA Carboxylase Deficiency. Metab Brain Dis 17, 13–18 (2002). https://doi.org/10.1023/A:1014096112916
Issue Date:
DOI: https://doi.org/10.1023/A:1014096112916