Hereditary sensory and autonomic neuropathy type I (HSAN I) is an autosomal dominant disease characterized by distal sensory loss, pain insensitivity, and autonomic disturbances. The major underlying causes of HSAN I are point mutations in the SPTLC1 gene. Patients with mutations in the SPTLC1 genes typically exhibit dense sensory loss and incidence of lancinating pain. Although most of these mutations produce sensory loss, it is unclear which mutations would lead to the painful phenotype. In this case series, we report that the V144D mutation in SPTLC1 gene may relate to both painful and painless peripheral neuropathies. The unique clinical phenotype of this mutation may guide clinical workup and treatment for patients with painful and painless neuropathies.
HSAN I is an autosomal dominant disease characterized by distal sensory loss, pain insensitivity and autonomic disturbances. The major underlying causes of HSAN I are mutations in the SPTLC1 gene, which encodes the first subunit of serine palmitoyltransferase (SPT). These mutations result in the formation of atypical neurotoxic sphingolipids and subsequent dysfunction in the peripheral nerves [
A 37-year-old woman presented with intense pain in her feet while walking. She began to feel water droplets burning through her feet at age 29. Her symptoms continued to progress to an intense burning and lightening-like pain while walking, as if her feet were scraped by sandpaper and then dipped in rubbing alcohol. The pain was so severe that she thought about cutting her feet off.
Examination was significant for severe pain in her feet; a simple touch was equivalent to a “bowling ball dropped on her skin”. She had high arched feet on exam (Figure
Feet of the presented cases: both presented with high arches.
A 74-year-old male presented with generalized numbness. He started to have significant numbness in his legs in his forties, which progressed to above his knees. At the time of visit, he had no sensation in his hands, fingers, and toes. His legs would jump when he lied down at night and he had ankle pain when he walked. He had cramps in his thighs, calves, and left arm. He had some hearing difficulties and tremors. Family history was significant for the daughter of the subject carrying the same mutation; she also had similar symptoms of generalized numbness. The subject also has two unaffected daughters and a sister who were offered genetic testing but they declined.
On exam, he had absent light touch and pinprick sensation below his knees and elbows. He had reduced vibratory sense below his knees. He was areflexic throughout. Strengths were 4+/5 in his hands and full strength in his legs. There was atrophy of the bilateral feet and hands, and he could not walk tandem, on toes or on heels. He had high arches bilaterally and his feet could not be easily brought into a neutral position (Figure
Common genetic polymorphisms have been shown to affect the development and perception of pain [
The authors declare that they have no conflicts of interest.
Dr. Ho conceptualized and drafted the manuscript. Dr. Jerath conceptualized the manuscript, critically reviewed the article, and provided revisions for intellectual content.
We would like to acknowledge Invitae Genetics and Alnylam Pharmaceuticals for their support in genetic testing.