L-2-Hydroxy-Glutarazidurie - eine seltene Differenzialdiagnose der Makrozephalie

Zusammenfassung

Wir berichten über ein neunjähriges Mädchen, welches wegen einer progredienten Makrozephalie und Schulschwierigkeiten vorgestellt wurde. Neben einer Lernbehinderung fand sich klinisch eine milde spastisch-ataktische Bewegungsstörung. Im MRT zeigten sich ausgedehnte Signalveränderungen der weißen Substanz. Biochemisch wurde eine L-2-Hydroxy-Glutarazidurie nachgewiesen, die als seltene Differenzialdiagnose bei der Makrozephalie berücksichtigt werden muss.

Abstract

We report on a 9-year-old girl who was referred to our department because of increasing macrocephaly and school problems. The neurological examination disclosed mild cerebellar dysfunction and positive pyramidal tract signs. An MRI of the brain revealed extensive signal alterations of the white matter. Biochemical investigations established the diagnosis of L-2-hydroxyglutaric aciduria which has to be kept in mind as a rare cause of macrocephaly.

Schlüsselwörter

Makrozephalie - Leukenzephalopathie - L-2-Hydroxy-Glutarazidurie

Key words

macrocephaly - leukoencephalopathy - L-2-hydroxyglutaric aciduria

Literatur

• 1 Aicardi J. Diseases of the Nervous System in Childhood. 2nd ed. Mac Keith Press, Cambridge 1998
• 2 Barbot C, Fineza I, Maria M. et al . L-2-Hydroxyglutaric aciduria: clinical, biochemical and magnetic resonance imaging in six Portuguese pediatric patients.  Brain Dev. 1997;  19 268-273
• 3 Barth P G, Hoffmann G F, Jaeken J. et al . L-2-hydroxyglutaric acidemia: a novel inherited neurometabolic disease.  Ann Neurol. 1992;  32 66-71
• 4 Barth P G, Hoffmann G F, Jaeken J. et al . L-2-hydroxyglutaric acidemia: clinical and biochemical findings in 12 patients and preliminary report on L-2-hydroxyacid dehydrogenase.  Inherit Metab Dis. 1993;  16 753-761
• 5 Brenner M, Johnson A B, Boespflug-Tanguy O. et al . Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease.  Nat Genet. 2001;  27 117-120
• 6 Hanefeld F, Kruse B, Bruhn H. et al . In vivo proton magnetic resonance spectroscopy of the brain in a patient with L-2-hydroxyglutaric acidemia.  Pediat Res. 1994;  35 614-616
• 7 Hoffmann G F, Jakobs C, Holmes B. et al . Organic acids in cerebrospinal fluid and plasma of patients with L-2-hydroxyglutaric aciduria.  Inherit Metab Dis. 1995;  18 189-193
• 8 Jansen G A, Wanders R J. L-2-hydroxyglutarate dehydrogenase: identification of a novel enzyme activity in rat and human liver. Implications for L-2-hydroxyglutaric acidemia.  Biochim Biophys Acta. 1993;  1225 53-56
• 9 Kaabachi N, Larnaout A, Rabier D. et al . Familial encephalopathy and L-2-hydroxyglutaric aciduria.  Inherit Metab Dis. 1993;  186 893
• 10 Moroni I, D'Incerti L D, Farina L. et al . Clinical, biochemical and neuroradiological findings in L-2-hydroxyglutaric aciduria.  Neurol Sci. 2000;  21 103-108
• 11 Topcu N, Jobard F, Halliez S. et al . L-2-hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1.  Hum Mol Genet. 2004;  13 2803-2811
• 12 der Knaap M S Van, Barth P G, Stronik H. et al . Leukencephalopathy with swelling and a discrepantly mild clinical course in eight children.  Ann Neurol. 1995;  37 324-334
• 13 Wilcken B, Pitt J, Heath D. et al . L-2-Hydroxyglutaric aciduria: three Australian cases.  Inherit Metab Dis. 1993;  16 501-504