Atypical vitamin B12-unresponsive methylmalonic aciduria in a sibship with severe progressive encephalomyelopathy: a new genetic disease?
We report on two siblings, a girl of 7 years and a boy of 2 years, who presented in infancy with hypotonia, athetoid movements, myopathy and severe developmental delay. The progressive clinical course was characterized by ophthalmoplegia, pyramidal tract signs, loss of visual contanct and failure to...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 1996
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| In: |
European journal of pediatrics
Year: 1996, Volume: 155, Issue: 5, Pages: 398-403 |
| ISSN: | 1432-1076 |
| DOI: | 10.1007/BF01955272 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/BF01955272
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| Author Notes: | E. Mayatepek, G.F. Hoffmann, R. Baumgartner, A. Schulze, C. Jakobs, F.K. Trefz, H.J. Bremer |
| Summary: | We report on two siblings, a girl of 7 years and a boy of 2 years, who presented in infancy with hypotonia, athetoid movements, myopathy and severe developmental delay. The progressive clinical course was characterized by ophthalmoplegia, pyramidal tract signs, loss of visual contanct and failure to thrive. The older sister died at the age of 7 years. The younger brother followed an almost identical clinical course. MRI of the brain revealed bilateral hypodensities and atrophy of the putamen. Neurophysiological investigations were consistent with peripheral neuropathy. Investigations for neurometabolic disorders in urine, plasma and CSF of both patients revealed a consistent increase of methylmalonic acid in urine, plasma and CSF as well as borderline low free GABA in CSF. Except for an inconstant elevation of lactate in the boy, metabolic acidosis, hypoglycaemia, episodic ketoacidosis, or hyperammonaemia, the usual concomitants of organoacidopathies, were absent in both children. Homocystinuria was excluded. Methylmalonic aciduria did not respond to antibiotic treatment, vitamin B12 therapy nor dietary protein restriction. Incorporation of [14C]propionate into protein in cultured fibroblasts was pathologically but inconsistently decreased. Both patients' cell lines showed only minimal response to hydroxocobalamin and normal methylmalonyl-CoA mutase activity. |
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| Item Description: | Im Titel ist 12 tiefgestellt Gesehen am 28.05.2024 |
| Physical Description: | Online Resource |
| ISSN: | 1432-1076 |
| DOI: | 10.1007/BF01955272 |