SHORT REPORT Osteoma of the calvaria in L-2-hydroxyglutaric aciduria A. Larnaout & R. Amouri & S. Neji & M. Zouari & N. Kaabachi & F. Hentati Received: 5 February 2007 / Submitted in revised form: 16 May 2007 / Accepted: 30 July 2007 # SSIEM and Springer 2007 Summary L-2-Hydroxyglutaric aciduria (L-2-OHGA) is a rare autosomal recessive neurometabolic disease linked to chromosome 14q21.1 and is caused by mutations in the gene that most likely encodes L-2- hydroxyglutarate dehydrogenase, which normally cata- lyses L-2-hydroxyglutarate to a-ketoglutarate. It is characterized by progressive mental deterioration, pyramidal and cerebellar syndromes, macrocephaly and marked polycystic white-matter degeneration mainly involving frontal lobes. Brain tumours of variable nature have frequently been observed in L-2- OHGA. We report a patient affected by this disease who at the age of 20 years developed a bone tumour involving the right frontal region of the calvaria. He had first presented at the age of 10 years with psychomotor delay, clumsy gait and moderate mental impairment. Examination showed macrocephaly, cer- ebellar ataxia and quadripyramidal syndrome. Brain MRI showed low signal intensities on T1-weighted images and high signal intensities on T2-weighted images in cerebral subcortical white matter. Serum and urinary amino acid assay was normal. Urinary 2- hydroxyglutaric acid was 1418 mmol/mol creatinine (controls <25). Analysis of the L-2-hydroxyglutarate dehydrogenase gene revealed a homozygous mutation in exon 2 (A320G). At the age of 20 years, an osteoma of the right frontal bone was diagnosed. This finding reinforces the opinion concerning the association of L- 2-OHGA and tumorigenesis and prompted us to verify the possible responsibility of some overproduced sub- stances in this disease for the development of tumours and to look for any correlation between the type of mutation in the L-2-OHGA gene and the tumorigenic potential observed in some patients affected by this disease. Abbreviations L-2-OHG acid L-2-hydroxyglutaric acid L-2-OHGA L-2-hydroxyglutaric aciduria L-2-Hydroxyglutaric aciduria (L-2-OHGA) is a rare autosomal recessive neurometabolic disease linked to chromosome 14q22.1 which was first reported in 1980 by Duran and colleagues (Duran et al 1980). Twelve years later, its clinical pattern was described (Barth et al 1992) and in 1994 its neuropathological features were established (Larnaout et al 1994). Recently, it has been found that L-2-OHGA is caused by mutations in the gene that most likely encodes L-2-hydroxyglutarate dehydrogenase, which normally catalyses L-2-hydrox- yglutarate to a-ketoglutarate. In one Tunisian family, a homozygous mutation in exon 2 (A320G) has been identified (Rzem et al 2004). The onset of the disease ranges from the neonatal stage to 44 years and the clinical pattern is characterized JIMD Short Report #087 (2007) Online DOI 10.1007/s10545-007-0576-0 Communicating editor: Cornelis Jakobs Competing interests: None declared A. Larnaout : R. Amouri : M. Zouari : F. Hentati Institut National de Neurologie, Ho ˆ pital la Rabta, Tunis, Tunisia S. Neji Service de Neuroradiologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia N. Kaabachi Laboratoire de Biochimie, Ho ˆ pital la Rabta, Tunis, Tunisia A. Larnaout (*) Institut National de Neurologie, La Rabta, 1007 Tunis, Tunisia e-mail: abdelmajid.larnaout@rns.tn