Identification of novel L2HGDH mutation in a large consanguineous Pakistani family- a case report

Muhammad Ikram Ullah, Abdul Nasir, Arsalan Ahmad, Gaurav Vijay Harlalka, Wasim Ahmad, Muhammad Jawad Hassan, Emma L. Baple, Andrew H. Crosby, Barry A. Chioza

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Background: L-2-hydroxyglutaric aciduria (L2HGA) is a progressive neurometabolic disease of brain caused by mutations of in L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene. Cardinal clinical features include cerebellar ataxia, epilepsy, neurodevelopmental delay, intellectual disability, and other clinical neurological deficits. Case presentation: We describe an index case of the family presented with generalised tonic-clonic seizure, developmental delay, intellectual disability, and ataxia. Initially, the differential diagnosis was difficult to be established and a SNP genome wide scan identified the candidate region on chromosome 14q22.1. DNA sequencing showed a novel homozygous mutation in the candidate gene L2HGDH (NM_024884.2: c.178G > A; p.Gly60Arg). The mutation p.Gly60Arg lies in the highly conserved FAD/NAD(P)-binding domain of this mitochondrial enzyme, predicted to disturb enzymatic function. Conclusions: The combination of homozygosity mapping and DNA sequencing identified a novel mutation in Pakistani family with variable clinical features. This is second report of a mutation in L2HGDH gene from Pakistan and the largest family with L2HGA reported to date.

Original languageEnglish
Article number25
JournalBMC Medical Genetics
Issue number1
Publication statusPublished - 20 Feb 2018
Externally publishedYes


  • Cerebellar ataxia
  • Developmental delay
  • Epilepsy
  • Intellectual disability
  • L-2-hydroxyglutaric aciduria
  • L2HGDH
  • Mutation
  • Pakistan


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