Background And Objectives: L-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 Settings: A 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 Methods: Genomic 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.

Results: All 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.

Conclusion: The 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074860PMC
http://dx.doi.org/10.5144/0256-4947.2014.107DOI Listing

Publication Analysis

Top Keywords

l-2-hydroxyglutaric aciduria
28
aciduria patients
16
arab patients
16
patients
14
l2hgdh gene
12
c169g mutation
12
l-2-hydroxyglutaric
8
features l-2-hydroxyglutaric
8
aciduria arab
8
patients exhibit
8

Similar Publications

Germline inactivating mutations of the SLC25A1 gene contribute to various human disorders, including Velocardiofacial (VCFS), DiGeorge (DGS) syndromes and combined D/L-2-hydroxyglutaric aciduria (D/L-2HGA), a severe systemic disease characterized by the accumulation of 2-hydroxyglutaric acid (2HG). The mechanisms by which SLC25A1 loss leads to these syndromes remain largely unclear. Here, we describe a mouse model of SLC25A1 deficiency that mimics human VCFS/DGS and D/L-2HGA.

View Article and Find Full Text PDF
Article Synopsis
  • L-2 hydroxyglutaric aciduria (L-2-HGA) is a rare genetic disorder that leads to various neurological symptoms and requires careful diagnosis for effective treatment.
  • In a case series of three patients, symptoms included febrile seizures, hyperactivity, and intellectual challenges, with one case showing cervical dystonia.
  • Brain MRIs of two patients revealed distinctive patterns associated with L-2-HGA, emphasizing the need for increased awareness and early diagnosis to enable the use of management strategies like riboflavin, levocarnitine, and dietary changes.
View Article and Find Full Text PDF
Article Synopsis
  • Metabolic/neurodegenerative encephalopathies cover various conditions in dogs and cats that have similar MRI features, complicating accurate diagnosis and often requiring multiple tests.
  • This study aimed to analyze MRI characteristics, classify conditions based on gray and white matter involvement, and compare findings with existing literature, involving 100 cases (81 dogs and 19 cats).
  • Notable findings included unusual MRI patterns, such as cerebellar nuclei changes in hepatic encephalopathy and specific white matter involvement in myelinolysis, along with unique effects of thiamine deficiency on various brain structures.
View Article and Find Full Text PDF

Focal dystonia in an adult with L-2- hydroxyglutaric aciduria.

Saudi Med J

July 2024

From the Neurology Department (Saleem), Al-Iman General Hospital; from the Radiology Department (Ul Islam), King Salman Hospital; form the Laboratory Department (Tasbahji), Al-Iman General Hospital, Riyadh, Kingdom of Saudi Arabia.

L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare disorder. The patients have psychomotor retardation, ataxia, macrocephaly, and epilepsy usually in childhood. We present a case of L-2-HGA who developed dystonia in the third decade of life.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!