Intracranial Volume May Be Used as Measure of Brain Development in Fabry Disease, Study Finds

The intracranial volume (ICV) in patients with Fabry disease is significantly lower than in healthy individuals, indicating an early onset of neurodevelopmental abnormality, according to researchers.

Their study, “Reduced Intracranial Volume in Fabry Disease: Evidence of Abnormal Neurodevelopment?” was published in the journal Frontiers in Neurology.

Fabry disease is characterized by the accumulation of globotriaosylceramide (GB3) — caused by a deficiency in the alpha-galactosidase A enzyme — in tissues and cells.

An accumulation of this type of fat can cause neurodevelopmental abnormalities, which if not caught early can lead to long-lasting damage.

But information on Fabry disease-associated central nervous system alterations is limited and restricted to specific brain tissues.

Researchers measured the intracranial volume (ICV) of Fabry patients and compared it with data from healthy controls, as a possible measure of abnormal brain development in Fabry disease.

ICV is an accurate brain volume measure, which combines the gray and white matter of the brain and the cerebrospinal fluid (CSF). This measure represents a proxy for the maximal brain growth obtained during development and maturation whose changes may represent a possible indicator of neurodevelopmental anomaly.

A total of 42 Fabry patients (15 males, 27 females) confirmed by genetic testing along with 38 healthy controls (same amount of males and females) participated in this study.

Only participants with no history of any neurologic or psychiatric condition or any other disease that could impact the central nervous system were included. The mean age of the participants was 43.3.

Researchers measured the intracranial volume of participants using volumetric magnetic resonance imaging (MRI). They also analyzed different components of intracranial volume individually (gray matter, white matter, and CSF).

A significant difference in mean intracranial volume was observed between Fabry patients (1267.8 ml) and healthy individuals (1379.8 ml). This means that overall, intracranial volume in Fabry patients was 8.1% lower than that of healthy controls.

However, no statistical difference was reported between the two groups regarding fractional tissue volumes of gray matter, white matter, and CSF, indicating these volumes were preserved during growth and development.

ICV reaches its peak volume early in childhood and remains so despite any changes to brain tissues. As such, the significantly reduced intracranial volume observed in Fabry patients in this study, despite preserved individual tissue volumes, indicates a “harmonious reduction of all intracranial tissue volumes,” researchers noted.

These results suggest an early onset of neurodevelopmental abnormality in Fabry disease, emphasizing the need for early diagnosis.

According to the authors, these results suggest that “in [Fabry disease] patients an abnormality of brain development is present, expanding the current knowledge about central nervous system involvement in [Fabry disease], further emphasizing the importance of an early diagnosis.”

More studies are necessary to understand whether this feature of the disease is part of “the spectrum of more generalized growth defects encountered in this pathology, or it represents an independent phenomenon,” the authors concluded.