Facial anomalies in D‐2‐hydroxyglutaric aciduria

Abstract

D-2-hydroxyglutaric aciduria is a rare autosomal recessive organic aciduria with variable clinical expression. The biochemical defect is still unknown, and genetic heterogeneity has been suggested. Here, we report on facial anomalies in two unrelated cases of D-2-hydroxyglutaric aciduria presenting with epileptic encephalopathy. In a review, we found that minor facial anomalies have been mentioned in three patients. A flat face with a broad nasal bridge and external ear anomalies were present in our patients and in reported cases. We suggest giving consideration to D-2-hydroxyglutaric aciduria as a cause of minor facial anomalies in epileptic encephalopathy of unknown origin.

D‐2‐hydroxyglutaric aciduria: A case with an intermediate phenotype and prenatal diagnosis of two affected fetuses

“…We present a child with D2HGA who has followed an intermediate course. One other similar case has been reported [Amiel et al, 1999]. Amiel et al [1999] also noted that several cases of D2HGA have had a flat face, broad nasal bridge, and external ear abnormalities and we noted similar changes in our patient.…”

“…One other similar case has been reported [Amiel et al, 1999]. Amiel et al [1999] also noted that several cases of D2HGA have had a flat face, broad nasal bridge, and external ear abnormalities and we noted similar changes in our patient. There are two previous reports of prenatal diagnosis for D2HGA that describe increased levels of D ‐2‐hydroxyglutaric acid in amniotic fluid in association with affected fetuses [Craigen et al, 1994; Muntau et al, 2000].…”

“…Almost all patients reported to date with D2HGA have followed either a mild or a severe clinical course and there has been a clear distinction between these two groups [van der Knaap et al, 1999a]. Children with the severe form present by the age of 3 months, usually with an epileptic encephalopathy and make little developmental progress [Amiel et al, 1999; van der Knaap et al, 1999a]. The epilepsy is often intractable.…”

Progress in understanding 2‐hydroxyglutaric acidurias

“…Currently, six cases of D,L-2-hydroxyglutaric aciduria (D,L-2-HGA) have been described, of which four were previously classified as D-2-HGA affected with a severe phenotype (Wagner et al 1998;Amiel et al 1999;Van der Knaap et al 1999a, b;Muntau et al 2000;Wajner et al 2002;Read et al 2005). D,L-2-HGA is biochemically characterized by moderately increased D-2-HG and L-2-HG in urine, mild increases of both metabolites in plasma, and a very slight elevation of D-2-HG in CSF and normal levels of L-2-HG (Table 8).…”

D‐2‐Hydroxyglutaric aciduria: Unravelling the biochemical pathway and the genetic defect

“…Cardiomyopathy and facial dysmorphic features are frequently reported in this group of D-2-HGA patients. The facial dysmorphia consist of a flat face with a broad nasal bridge and external ear anomalies (Amiel et al 1999). In addition, spondyloenchondrodysplasia has been reported in three patients with D-2-HGA, all born to nonconsanguineous parents (Bayar et al 2005;Honey et al 2003;Talkhani et al 2000).…”