D-2-hydroxyglutaric aciduria: further clinical delineation.

Area of Science:

• Neurology
• Metabolic Disorders
• Neuroimaging

Background:

• D-2-hydroxyglutaric aciduria is a recognized neurometabolic disorder with distinct severe and mild phenotypes.
• The mild phenotype's clinical presentation was previously variable and poorly defined.
• Limited data existed for characterizing the full spectrum of D-2-hydroxyglutaric aciduria.

Purpose of the Study:

• To further define the clinical, biochemical, and neuroimaging characteristics of D-2-hydroxyglutaric aciduria.
• To clarify the relationship between the severe and mild phenotypes.
• To identify common and distinguishing features across different phenotypes.

Main Methods:

• Collected clinical, biochemical, and neuroimaging data from 8 additional patients (4 severe, 4 mild).
• Analyzed and compared findings between severe and mild phenotypes.
• Reviewed neuroimaging (MRI) for consistent abnormalities.

Main Results:

• The mild phenotype shares essential characteristics with the severe phenotype.
• Common findings across both phenotypes include epilepsy, hypotonia, and psychomotor retardation.
• Severe phenotype is associated with episodic vomiting, cardiomyopathy, inspiratory stridor, and apneas.
• Consistent MRI findings include lateral ventricle enlargement (occipital > frontal), subependymal cysts, and delayed cerebral maturation.
• Later MRI may show multifocal white-matter abnormalities; vascular abnormalities were noted in two patients.

Conclusions:

• The mild phenotype of D-2-hydroxyglutaric aciduria is more defined and shares core features with the severe phenotype.
• Epilepsy, hypotonia, and psychomotor retardation are key indicators regardless of phenotype.
• Neuroimaging, particularly MRI, reveals consistent abnormalities indicative of the disorder's impact on brain development.