LAUSR

Compound heterozygous and sometimes homozygous mutations in the DARS2 gene have been described as a cause of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL; Online Mendelian Inheritance in Man: 611105). LBSL is characterized by progressive spasticity, ataxia, and dorsal column dysfunction usually starting during childhood or adolescence combined with distinct leukoencephalopathy of the brainstem and spinal cord. Here we describe 2 brothers with isolated, slowly progressive spastic paraparesis, proprioceptive dysfunction, and an onset in adulthood mimicking hereditary spastic paraplegia (HSP). Patient L-15088 (Fig. 1D), a 44-year-old man, had noticed leg weakness when playing soccer at aged 18 years. His walking distance decreased gradually, and he described muscle cramps after extensive exercise. In the neurological examination, he presented with spastic paraparesis (4/5 on the Medical Research Council scale), brisk muscle tendon reflexes of the lower extremities, bilateral Babinski signs, and spastic-ataxic gait (modified Ashworth scale, 2). Vibration sensation was absent in the lower extremities, and positional sense was impaired. Walking distance was 20 m without and 500 m with walking aids (see Video 1). The 50-year-old brother L-15089 noticed reduced leg strength during marches in military training at the age of 19 years. He additionally described urinal urge symptoms. On examination, L-15089 was slightly less affected than L-15088 with an unaided walking distance of 200 m. Symptoms and leg spasticity were more pronounced on the left body side (modified Ashworth scale, 2; see Video 2). In both brothers, there