Rotthier et al. (2010) reported 4 unrelated probands with hereditary sensory neuropathy. Three probands had adult onset (ages 38, 37, and 52 years) of distal sensory loss. The presenting symptoms in these patients included loss of touch and ... Rotthier et al. (2010) reported 4 unrelated probands with hereditary sensory neuropathy. Three probands had adult onset (ages 38, 37, and 52 years) of distal sensory loss. The presenting symptoms in these patients included loss of touch and vibration in the feet, dysesthesia and severe panmodal sensory loss in the upper and lower limbs, and distal lower limb sensory loss with ulceration and osteomyelitis necessitating amputation of the right great toe. Two patients had associated distal muscle weakness, but none of the patients had autonomic dysfunction. One patient had additional features, including scoliosis, focal epilepsy, hyperreflexia of the upper limbs, and clenched hands. Nerve conduction velocity studies in these patients showed an axonal sensorimotor neuropathy, and biopsy in 1 patient showed an axonal neuropathy particularly affecting unmyelinated fibers. The fourth proband, a Czech, had a more severe disorder, with onset at age 5 years of gait difficulties and foot deformities. He had ulceration and osteomyelitis of the lower limbs, weakness of the lower limbs, and autonomic dysfunction, mainly anhidrosis. Nerve conduction velocity studies in this patient indicated a mixed axonal and demyelinating sensorimotor neuropathy.
In a study of 78 unrelated patients with HSAN, Rotthier et al. (2010) found that 4 had heterozygous mutations in the SPTLC2 gene (605713.0001-605713.0003). The mother of 1 of the patients, who also carried the mutation, had some ... In a study of 78 unrelated patients with HSAN, Rotthier et al. (2010) found that 4 had heterozygous mutations in the SPTLC2 gene (605713.0001-605713.0003). The mother of 1 of the patients, who also carried the mutation, had some evidence of distal sensory neuropathy, but also had diabetes, which may have complicated the findings. In vitro and in vivo yeast studies indicated that the mutations resulted in partial or complete loss of enzyme activity. In addition, the 3 mutations cause the formation of the neurotoxic metabolite 1-deoxysphinganine in HEK293 cells and patient lymphoblasts. These findings were similar to those observed with SPTLC1 mutations, which cause HSAN1A (Penno et al., 2010), suggesting a common pathomechanism.