Skin Biopsy Used for the Diagnosis of Hereditary Diffuse Leukoencephalopathy With Spheroids

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare leukodystrophy of the central nervous system. We present two patients from unrelated families with late-onset HDLS. Patient 1 was a 50-year old woman who developed blurred speech and difficult dressing at 48 and epilepsy and uroclepsia one year later. Patient 2 was a 51-year old man with a 10-month history of slurred speech and cognitive decline. Both patients had several brain MRI studies that showed persistent patchy hyperintensities on DWI images (Figure 1) . These imaging findings lead us to perform genetic testing. We identified two“likely pathogenic”variants of c.2264T>C (p.Leu755Pro) (patient 1) and c.1957T>C (p.Cys653Arg) (patient 2) in the CSF1R gene. Skin biopsy revealed the characteristic swelling of unmyelinated axons (spheroids) (Figure 2) . Although brain biopsy is the gold standard for the diagnosis of this condition, 1 skin biopsy may be an effective and efficient alternative for diagnosing HDLS.