Hereditary Sensory and Autonomic Neuropathy Type Iv

Several types of hereditary sensory and autonomic neuropathies (HSAN) are reported in literatures. We describe here a case of type IV HSAN, the second commonest variety of HSAN and attempt to present a short review of literature. Families of these children need support, proper guidance and counseling for taking better care of the diseased. The goal should be to help them achieve independent function with minimal physical limitations.


INTRODUCTION
Hereditary sensory and autonomic neuropathies (HSAN) are a group of genetic disorders associated with varying degrees of sensory and autonomic dysfunction.Several types have been described and many more are being added to the list.Type III HSAN (familial dysautonomia) is the commonest followed by Type IV.Type IV HSAN is also referred to as hereditary sensory neuropathy with anhidrosis or congenital insensitivity to pain with anhidrosis.As the prognosis for HSAN disorders are improving, the aim of this article is to help readers to increase the ability to accurately diagnose this condition, understand the natural course of the disease and institute appropriate treatment measures.

CASE REPORT
Three year and ten month old boy born to parents of second-degree consanguinity with mild developmental delay was brought with history of multiple fractures from the age of two years.He first sustained fracture of right forearm after a fall, and later had fractures in left forearm, left distal leg and right upper leg.Fractures were treated in cast and parents noticed that he does not cry excessively after fall or during cast application.Eventhough, tears used to come while crying they noted that he has decreased sweating.Since three months, they noticed self-mutilation also.There was history of recurrent high-grade fever, but no febrile convulsions.On examination, the anthropometric measurements were normal for his age.He was cooperative and playful.He had thin scalp hair, dry skin, normal speech, normal eyes and teeth, frontal bossing and prominence of mandible on right side.There were no features suggestive of rickets.Cardio respiratory and per abdominal examinations were normal.He had multiple ulcers on his fingers, resorption of the fingertips and dystrophic nails.He had lateral bowing of the right forearm with terminal restriction of pronation and supination.The right leg showed bony hard swelling in the upper third along with crepitus and painless abnormal mobility.Lateral bowing of the left leg in its distal third was noted without abnormal mobility.The spine was normal.
Neurological evaluations showed normal cranial nerves.Though mild hypotonia was noted the muscle power was relatively normal.Sensory examination showed decreased pain, touch and temperature perception.Deep tendon reflexes were diminished, but plantar reflex showed flexor response.Blood investigations revealed microcytic hypochromic anemia with low MCV, MCH, MCHC and raised reticulocyte count.The ESR was normal and CRP was negative.Ultrasound abdomen was normal.
Radiographs showed resorption of distal phalanges of thumb, index and middle fingers on both hands (Figure 1a and b), fracture of the right upper tibia in healing stage with exuberant callus formation (Figure 2a and b), bowing of left tibia and bilateral radius and ulna (Figure 3 and 4).

DISCUSSION
The diagnosis of HSAN is based on clinical features, degree of sensory and autonomic dysfunction and biochemical evaluation.HSAN Type IV is transmitted in an autosomal recessive pattern like Type II and III. 1 HSAN IV is shown to be caused by mutation in the NTRK1 gene located on chromosome 1 (1q21-q22).Due to the mutation, the nerve growth factor (NGF) dependent neurons namely the small sensory and sympathetic neurons fail to survive. 2,3 he incidence is noted to be more in consanguineous marriages.Onset of the disease occurs in infancy. 1,2  diagnosis of HSAN type IV is based on three clinical criteria's namely anhidrosis, decreased pain perception and mental retardation.However, the degree of expression of these features, especially intelligence can vary. 1,2 e IV HSAN is characterised by involvement of ectodermal structures like skin, bone and nervous system.2][3][4] This leads to episodic fever and extreme hyperthermia, which could in turn cause febrile convulsions.The anhidrosis is almost complete on the trunk and extremities while other areas are variably affected.Secondarily, thickening of skin, lichenification of palms, dystrophy of nails and loss of scalp hair can occur. 1,2,4 At from anhidrosis other autonomic dysfunctions are mild to absent.Postural hypotension with compensatory tachycardia can occur, but not episodic hypertension as seen in type III.Also unlike in type III HSAN, gastrointestinal dysmotility, vomiting, dysautonomic crisis, insensitivity to hypoxia and hypercapnia and acrocyanosis are uncommon in type IV HSAN 3,5 (Table 1).
The second characteristic feature of type IV HSAN is gross reduction in superficial, deep and visceral pain.This leads to high incidence of self-mutilation, trophic ulcers, auto-amputation, corneal scarring and fractures 1,4,5 which bring these children to the Orthopaedic surgeon.Delay in healing of fractures has been noted.Repeated trauma to bone and joints leads to deformities, osteomyelitis and Charcot joints.Temperature sensation is also decreased, but deep tendon reflexes are usually preserved.Hypotonia and delayed developmental milestones are seen in early years, but the muscle tone and strength improves with age.These children can have learning problems, hyperactivity and emotional lability. 1,5 al nerve biopsy shows absence of unmyelinated fibres.Skin biopsy shows deficient unmyelinated C fibres in the epidermis and absent or hypoplastic dermal sweat glands without innervation.The lack of sweat gland innervation accounts for the severe anhidrosis. 1 Absence of a normal axonal flare in response to intradermal histamine phosphate is unique to all HSAN and occurs due to absence or deactivation of the unmyelinated C-fibres which are essential for producing this response. 1dical management of these patients is directed to control of hyperthermia, prevention of self-mutilation and treatment of orthopaedic problems causing severe and debilitating deformities.
Professor of Orthopaedics 1 Assoc.Professor of Orthopaedics Correspondence should be sent to: sandeep_vijayan@yahoo.co.inKerala Journal of Orthopaedics 2013;26(1): 27-30 Case reportHowever, density of the bones were normal.Nerve conduction study showed decreased SNAP in both upper limbs, decreased CAMP in both peroneal nerves and absent sympathetic stimulation in upper and lower limbs.Intradural injection of histamine produced a suboptimal wheal and flare response.The diagnosis of HSAN type IV or congenital insensitivity to pain with anhidrosis was made.Sural nerve biopsy, skin biopsy and genetic analysis were suggested; however, parents were not willing for the tests.Child was given hematinics and bilateral knee-ankle-foot orthosis.

Fig. 3 .Fig. 4 .
Fig. 3. Anteroposterior radiograph of left forearm showing normal density and mal-union of radius with bowing deformity