Hereditary Sensory and Autonomic Neuropathy

Hereditary sensory and autonomic neuropathies are a group of inherited disorders with predominant loss of pain and temperature sensation and variable autonomic dysfunction, leading to painless injuries, ulcers and mutilation. Types I to VIII are named by gene: HSAN I (SPTLC1, SPTLC2, dominant, adult onset), II (WNK1/HSN2, recessive), III (familial dysautonomia, IKBKAP/ELP1), IV (NTRK1, congenital insensitivity to pain with anhidrosis), V (NGF), and others.

Pathophysiology. Genetic defects in sphingolipid synthesis, neurotrophin signalling or axonal transport cause degeneration of small sensory and autonomic neurons.

Loss of pain and temperature in the distal limbs, with painless injuries, foot ulcers, osteomyelitis, Charcot joints, acromutilation, lancinating pain (HSAN I), sweating abnormalities, recurrent infections, corneal ulcers and, in recessive types, early onset with self-mutilation, fever from anhidrosis (HSAN IV) and developmental delay. Hearing loss and cough occur in some types.

Red flags.

• Unexplained hyperpyrexia with anhidrosis in a child.
• Spreading foot infection or osteomyelitis.

Clinical examination of pain and temperature sensation. Nerve conduction studies show reduced or absent sensory responses, and skin biopsy shows reduced epidermal nerve fibres. Genetic panel or exome sequencing confirms the diagnosis. Serum deoxysphingolipids (HSAN I). Imaging of bones for osteomyelitis and Charcot arthropathy.

Differential diagnosis.

• Diabetic and other acquired small fibre neuropathy, leprosy, and amyloid neuropathy.
• Syringomyelia, tabes dorsalis and Charcot-Marie-Tooth disease type 2B.
• Fabry disease and Tangier disease.

No disease modifying treatment exists (oral L-serine for HSAN I is under study). Care focuses on injury prevention.

Foot and skin care. Daily inspection, protective footwear and orthoses, prompt treatment of ulcers (debridement, offloading and antibiotics), and podiatry. Osteomyelitis needs prolonged antibiotics and sometimes surgery.

Safety. Education on injury avoidance, protective dental care (mouthguards for self-biting in children), corneal protection with lubricants, and temperature regulation in anhidrosis (cooling).

Autonomic features. Orthostatic hypotension: fluids, salt, fludrocortisone. Gastrointestinal care and treatment of respiratory complications in dysautonomia.

Pain. Lancinating pain: gabapentin, carbamazepine.

Orthopaedic care. Treat Charcot joints and deformity.

Monitoring. Foot examination at each visit, growth, development and autonomic symptoms.

Referral and escalation. Refer to neurology, podiatry, orthopaedics and genetics.

Special groups. Genetic counselling and prenatal testing for recessive types.