• Muhammad Faiyaz-Ul-Haque, Moeenaldeen D Al-Sayed, Eissa Faqeih, Masood Jamil, Anjum Saeed, Mohamed Saleh Amoudi, Namik Kaya, Halah Abalkhail, Ahmed Al-Abdullatif, Mohamed Rashed, Mohammed Al-Owain, Iskra Peltekova, and Syed H E Zaidi.
• Dr. Muhammad Faiyaz-Ul-Haque, Department of Pathology,, College of Medicine,, King Khaled University Hospital,, King Saud University, T: 966-11-4699377, F: +966-11-4672462, mfhaque@ksu.edu.sa.
• Ann Saudi Med. 2014 Mar 1; 34 (2): 107-14.

Background And ObjectivesL-2-hydroxyglutaric aciduria is a neurometabolic disorder with autosomal recessive mode of inheritance in which patients exhibit elevated L-2-hydroxyglutaric acid in body fluids, central nervous system manifestations, and increased risk of brain tumor formation. Mutations in L2HGDH gene have been described in L-2-hydroxyglutaric aciduria patients of different ethnicities. The present study was conducted to perform a detailed clinical, imaging and genetic analysis.Design And SettingsA cross-sectional clinical genetic study of 16 L-2-hydroxyglutaric aciduria patients from 4 Arab consanguineous families examined at the metabolic clinic of the hospital.Patients And MethodsGenomic DNA was isolated from the blood of 12 patients and 10 unaffected family members, and the L2HGDH gene was sequenced. DNA sequences were compared to the L2HGDH reference sequence from GenBank.ResultsAll patients exhibit characteristic clinical, biochemical, and imaging features of L-2-hydroxyglutaric aciduria, and 4 patients exhibited increased incidence of brain tumors. The sequencing of the L2HGDH gene revealed the c.1015delA, c.1319C > A, and c.169G > A mutations in these patients. These mutations encode for the p.Arg339AspfsX351, p.Ser440Tyr, and p.Gly57Arg changes in the L2HGDH protein, respectively. The c.169G > A mutation, which was shown to have a common origin in Italian and Portuguese patients, was also discovered in Arab patients. Finding of the homozygous c.159T SNP associated with the c.169G > A mutation in Arab patients points to an independent origin of this mutation in Arab population.ConclusionThe detailed description of clinical manifestations and L2HGDH mutation in this study is useful for diagnosis of L-2-hydroxyglutaric aciduria in Arab patients. While reoccurrence of an L2HGDH mutation in L-2-hydroxyglutaric aciduria patients of different ethnicity is extremely rare, the c.169G mutation has an independent origin in Arab patients. It is likely that this mutation may also be present in patients of other ethnicities.

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