Endocrine, nutritional and metabolic diseases
Metabolic disorders
Autosomal recessive
14q21.3
L-2-Hydroxyglutaric Aciduria is a rare autosomal recessive disorder associated with progressive brain damage. Symptoms exhibited by affected individuals include cerebellar ataxia, seizures, hypotonia and macrocephaly in most cases. L-2-Hydroxyglutaric Aciduria results from mutations in Duranin (L2HGDH) gene.
| Subject ID | Country | Sex | Family History | Parental Consanguinity | HPO Terms | Variant | Zygosity | Mode of Inheritance | Reference | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|
| 236792.1.1 | Saudi Arabia | Male | Yes | Yes | Global developmental delay; Febrile seiz... Global developmental delay; Febrile seizure (within the age range of 3 months to 6 years)  | NM_024884.2:c.1015delA | Homozygous | Autosomal, Recessive | Sass et al. 2008 | Patient from family ... |
| 236792.1.2 | Saudi Arabia | Male | Yes | Yes | Global developmental delay Global developmental delay | NM_024884.2:c.1015delA | Homozygous | Autosomal, Recessive | Sass et al. 2008 | Patient from family ... |
| 236792.2.1 | Saudi Arabia | Female | Yes | Yes | Global developmental delay Global developmental delay | NM_024884.2:c.467G>T, NM_024884.2:c.1319C>A | Heterozygous | Autosomal, Recessive | Sass et al. 2008 | Patient from family ... |
| 236792.2.2 | Saudi Arabia | Male | Yes | Yes | Global developmental delay Global developmental delay | NM_024884.2:c.467G>T, NM_024884.2:c.1319C>A | Heterozygous | Autosomal, Recessive | Sass et al. 2008 | Patient from family ... |
| 236792.2.3 | Saudi Arabia | Female | Yes | No | Global developmental delay Global developmental delay | NM_024884.2:c.467G>T, NM_024884.2:c.1319C>A | Heterozygous | Autosomal, Recessive | Sass et al. 2008 | Patient from family ... |
| 236792.2.4 | Saudi Arabia | Male | Yes | No | Global developmental delay Global developmental delay | NM_024884.2:c.467G>T, NM_024884.2:c.1319C>A | Heterozygous | Autosomal, Recessive | Sass et al. 2008 | Patient from family ... |
| 236792.3.1 | Lebanon | Male | Yes | Yes | Global developmental delay; Hypothyroid... Global developmental delay; Hypothyroidism | NM_024884.2:c.164G>A, NM_024884.2:c.1115delT | Heterozygous | Autosomal, Recessive | Sass et al. 2008 | Patient from family ... |
| 236792.3.2 | Lebanon | Female | Yes | Yes | Global developmental delay; Hypothyro... Global developmental delay; Hypothyroidism | NM_024884.2:c.164G>A, NM_024884.2:c.1115delT | Heterozygous | Autosomal, Recessive | Sass et al. 2008 | Patient from family ... |
| 236792.4 | Tunisia | Female | Yes | Yes | Intellectual disability, mild; Macrocep... Intellectual disability, mild; Macrocephaly; Gait ataxia; Seizure | NM_024884.3:c.241A>G | Homozygous | Autosomal, Recessive | Rzem et al, 2004 | Unaffected parents a... |
| 236792.5.1 | Lebanon | Female | Yes | Yes | Gait ataxia; Seizure; Gait ataxia; Seizure; | NM_024884.3:c.528G>T | Homozygous | Autosomal, Recessive | Rzem et al, 2004 | |
| 236792.5.2 | Lebanon | Female | Yes | Yes | | NM_024884.3:c.528G>T | Homozygous | Autosomal, Recessive | Rzem et al, 2004 | Sibling of 236792.5.... |
| 236792.5.3 | Lebanon | Female | Yes | Yes | | NM_024884.3:c.528G>T | Homozygous | Autosomal, Recessive | Rzem et al, 2004 | |
| 236792.5.4 | Lebanon | Male | No | Yes | | NM_024884.3:c.528G>T | Homozygous | Autosomal, Recessive | Rzem et al, 2004 | |
| 236792.5.5 | Lebanon | Female | Yes | No | | NM_024884.3:c.528G>T | Homozygous | Autosomal, Recessive | Rzem et al, 2004 | |
| 236792.5.6 | Lebanon | Female | Yes | No | | NM_024884.3:c.528G>T | Homozygous | Autosomal, Recessive | Rzem et al, 2004 | |
| 236792.5.7 | Lebanon | Male | No | Yes | | NM_024884.3:c.528G>T | Homozygous | Autosomal, Recessive | Rzem et al, 2004 | |
| 236792.5.8 | Lebanon | Male | No | Yes | | NM_024884.3:c.528G>T | Homozygous | Autosomal, Recessive | Rzem et al, 2004 |
Periasamy et al. (2008) reported a 19-year old male born to non-consanguineous healthy parents who presented with an 11-year history of mental subnormality, intellectual deterioration and recurrent generalized tonic-clonic seizures. GC-MS studies revealed elevated concentration of L-2-hydroxyglutaric acid in the urine confirming L-2-hydroxyglutaric aciduria.
Duran et al. (1980) described a 5-year old boy of Moroccan origin with psychomotor retardation, dystrophy and delayed skeletal age. The diagnosis was confirmed by capillary gas chromatography.
Moammar et al. (2010) reviewed 248 newborns diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. 8 cases of 2-Hydroxyglutaricacidemia were reported and incidence of the disorder was estimated to be 5 in 100,000 live births in the cohort.
Larnaout et al. (1994) reported 3 brothers with a progressive neurological disorder associated with L-2-hydroxyglutaric aciduria.