Spondyloenchondromatosis with D-2-hydroxyglutaric aciduria: a report of a second patient with this unusual combination

Abstract

Spondyloenchondromatosis (SEM) is a rare skeletal dysplasia which presents with multiple enchondromata in the metaphyses of the long bones associated with dysplastic vertebral bodies. It is probably heterogeneous. We have investigated and documented a male infant in South Africa with spondyloenchondromatosis and persistent D-2-hydroxyglutaric aciduria (D2HA). D2HA is a neurometabolic disorder whose enzymatic basis is still undefined. A girl in England with a similar clinical, radiological and biochemical phenotype has previously been reported by Talkhani et al. [(2000). Skel Radiol 7:215-2921]. There is at present a lack of a plausible pathogenetic relationship between the two components of the disorder but a contiguous gene syndrome or a pleiotropic gene could be considered. Whatever the underlying mechanism this case report confirms its nosological entity.

Progress in understanding 2‐hydroxyglutaric acidurias

“…*Unknown (n = 2)D-2-HGA type I and type II were excluded: no mutations detected in D2HGDH or IDH2 Kranendijk et al 2010bCombinedIncreased D-2-HG and L-2-HGWagner 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Van der Knaap et al 1999a; b; Muntau et al 2000; Wajner et al 2002; Read et al 2005D,L-2-HGA (n = 11)6 published pts.5 unpublished pts. *Skeletal dysplasia (n = 6)3 published pts.Talkhani et al 2000; Honey et al 2003; Bayar et al 20053 unpublished pts. *

* Unpublished patients have been diagnosed in our laboratory

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“…The proband was diagnosed at 1 year with a crippling form of skeletal dysplasia, and global developmental delay that improved in her second year of life. The second patient was a male infant diagnosed at 6 months with skeletal dysplasia, and mild motor and mental delay (Honey et al 2003). Urinalysis revealed increased D-2-HG.…”

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

“…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). Magnetic resonance imaging (MRI) of the brain of severely affected patients typically shows signs of delayed cerebral maturation, ventricular white-matter abnormalities, and the presence of subependymal cysts in the first months of life.…”

Novel cases of D-2-hydroxyglutaric aciduria withIDH1orIDH2mosaic mutations identified by amplicon deep sequencing

“…Further reports of MC-HGA and D-2HGA are required to determine if patients with somatic IDH1 or IDH2 mosaicism have an increased risk of malignancies. This is of particular interest considering the fact that a patient diagnosed with metaphyseal chondromatosis with urinary excretion of D-2HG25 died after suffering from acute myeloid leukaemia (EM Honey, personal communication, 2010). Although no DNA analysis had been performed in this patient, the rarity of this combination of radiographic and metabolic findings lends support to the suggestion that perhaps the same pathogenic mechanism was involved.…”