Dr Ira Shah
MD, DCH (Gold Medalist), FCPS, DNB

A 5 year old female child, 3rd of 3 siblings born of third degree consanguineous marriage presented with intermittent fever since birth, self mutilation since 2½ years of age and ulcer over left middle toe with blackening since 10-12 days. Other 2 elder siblings had died (one due to fever at 2 months and second at 3 months due to altered sensorium). She was immunized till date, however there was no history of crying on receiving injections. She had multiple ulcers in the past and she required amputation of the left great toe due to gangrene at the age of 4½ years. Her milestones were delayed. At present she was able to only speak bisyllables and walk without support. On examination, there was an ulcer over the left second toe and she had absent left great toe. She had bitten off the distal phalynx of the right index finger (Figure 1).



Her both elbows had chronic ulcers and dentition was delayed. On CNS system examination, her motor system was normal and she had absent pain sensation on sensory system examination. A differential diagnosis of Hereditary sensory neuropathy & Lesch Nyhan syndrome was considered. Her Nerve conduction velocity showed peripheral neuropathy predominantly sensory with absent sensory conduction. Pilocarpine test showed presence of miosis in the eyes. Her sural nerve biopsy revealed mild fibrosis and electron microscopy could not be done. Her developmental Quotient was < 79 suggestive of mild mental delay. Thus, she was diagnosed as a case of Hereditary sensory neuropathy.

5 clinical different entities have been described under hereditary sensory and autonomic neuropathies – all characterized by progressive loss of function that predominantly affects the peripheral sensory nerves. Their incidence has been estimated to be about 1 in 25,000.

Type I (Hereditary Sensory Radicular Neuropathy): It is the most common of the hereditary sensory and autonomic neuropathies (HSAN). It is transmitted as autosomal dominant trait and is characterized by a sensory deficit in the distal portion of the lower extremities, chronic perforating ulcerations of the feet and progressive destruction of underlying bones. Symptoms appear in late childhood on early adolescence with trophic ulcers as pain sensation is affected more. Many patients have accompanying nerve deafness and atrophy of the peroneal muscles. Histopathologic examination reveals a marked reduction in the number of unmyelinated fibers. Motor nerve conduction velocities are normal, but the sensory nerve action potentials are absent.

Type II (Congenital Sensory Neuropathy): It is characterized by onset of symptoms in early infancy or childhood. Upper & lower extremities are affected with chronic ulcerations and multiple injuries to fingers and feet. Pain sensation is affected predominantly and deep tendon reflexes are reduced. Autoamputation of the distal phalanges is common and so is neuropathic joint degeneration. The NCV shows reduced or absent sensory nerve action potentials and nerve biopsy shows total loss of myelinated fibers and reduced numbers of unmyelinated fibers. It is inherited as an autosomal recessive condition.

Type III (Familial dysautonomia, Riley-Day syndrome): It is an autosomal recessive disorder seen predominantly in Jews of eastern European descent. Patients present with sensory and autonomic disturbances. Newborns have absent or weak suck reflex, hypotonia and hypothermia. Retarded physical development, poor temperature and motor in coordination are seen in early childhood. Other features include reduced or absent tears, depressed deep tendon reflexes, absent corneal reflex, postural hypotension and relative indifference to pain. Scoliosis is frequent. Intelligence remains normal. Many patients die in infancy and childhood. Lack of flare with intradermal histamine is seen. Histopathology of peripheral nerve shows reduced number of myelinated and non-myelinated axons. The catecholamine endings are absent.

Type IV (Congenital Insensitivity to Pain and Anhidrosis): It is an autosomal recessive condition and affected infants present with episodes of hyperthermia unrelated to environmental temperature, anhidrosis and insensitivity to pain. Palmar skin is thickened and charcot joints are commonly present. NCV shows motor and sensory nerve action potentials to be normal. The histopathology of peripheral nerve biopsy reveals absent small unmyelinated fibers and mitochondria are abnormally enlarged.

Type V (Hereditary Sensory and Autonomic Neuropathy): It also manifests with congenital insensitivity to pain & anhidrosis. There is a selective absence of small myelinated fibers differentiating it from type 4.

Treatment is symptomatic for the ulcers.