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Table of Contents
CASE REPORT
Year : 2012  |  Volume : 15  |  Issue : 2  |  Page : 134-136
 

A case of hereditary sensory autonomic neuropathy type IV


1 Department of Pediatrics, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India
2 Child Development Clinic, KLE University's JN Medical College, Belgaum, Karnataka, India

Date of Submission10-Nov-2010
Date of Decision12-Dec-2010
Date of Acceptance09-Mar-2011
Date of Web Publication13-Apr-2012

Correspondence Address:
G P Prashanth
Department of Pediatrics, SDM College of Medical Sciences and Hospital, Sattur, Dharwad-580 009, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-2327.94999

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   Abstract 

Hereditary sensory autonomic neuropathy type IV (HSAN -IV), also known as congenital insensitivity to pain with anhidrosis, is a very rare condition that presents in infancy with anhidrosis, absence of pain sensation and self -mutilation. Developmental delay and mental retardation are usually present. Ultrastructural study of the peripheral nerves demonstrates loss of the unmyelinated and small myelinated fibers. We here report a 8 year -old boy with HSAN IV with typical clinical features where the diagnosis was supported by nerve biopsy findings. However, our case was unusual since mental development was normal.


Keywords: Hereditary sensory autonomic neuropathy, insensitivity to pain, self-mutilation


How to cite this article:
Prashanth G P, Kamate M. A case of hereditary sensory autonomic neuropathy type IV. Ann Indian Acad Neurol 2012;15:134-6

How to cite this URL:
Prashanth G P, Kamate M. A case of hereditary sensory autonomic neuropathy type IV. Ann Indian Acad Neurol [serial online] 2012 [cited 2019 Jun 24];15:134-6. Available from: http://www.annalsofian.org/text.asp?2012/15/2/134/94999



   Introduction Top


Hereditary sensory and autonomic neuropathy type IV (HSAN IV), also called as congenital insensitivity to pain with anhidrosis (CIPA) or Nishida syndrome [1] is a rare autosomal recessive condition seen in children. [2],[3] We present clinical and nerve biopsy images of a 13-year-old boy with classical manifestations of CIPA.


   Case Report Top


A 8-year-old boy, born to a healthy non-consanguineous South Indian couple, presented with history of self-mutilation starting in infancy soon after primary dentition. There were repeated episodes of high fever in summer which was poorly responding to antipyretics. His developmental milestones were normal. There was no similar history in the family, with one younger sibling being healthy. On examination, there were signs of self-mutilation in the form of ulcerations of the lower lip, tongue, and oral mucosa. Skin, especially over the palms and soles was dry, coarse and mildly hyperkeratotic. Neurological examination revealed a generalized absence of response to temperature and painful stimuli. Touch, position, and vibration senses were intact. Tendon reflexes and plantar responses were normal. There was no cranial nerve palsy except for absent corneal reflex. Tests for autonomic function were normal.

On investigation, serum uric acid levels and the nerve conduction studies (motor and sensory) were normal. A bedside sweat test using pilocarpine showed the total absence of sweating. A full-thickness skin biopsy showed normal sweat glands. Sural nerve biopsy findings were consistent with hereditary sensory autonomic neuropathy [Figure 1]. IQ assessment using Binet-Kamat test showed a normal mental development for age (IQ=97). The child was lost to follow-up and presented to us 5 years later with extensive ulcers over upper limbs and neck [Figure 2]. There was substantial loss of tissue around the lips [Figure 3]. His left lower leg was amputated for non-resolving osteomyelitis 6 months back. The boy succumbed to fulminant sepsis with shock with profound DIC and massive upper GI bleed.
Figure 1: Mutilation of upper limb and fingers. Also note extensive ulcers involving the hand

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Figure 2: Clinical photograph showing self-mutilation of lower lip with skin changes

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Figure 3: Sural nerve biopsy showing reduced small myelinated fibers (unmyelinated fibers are shown in the subset). Large myelinated nerve fibers are normal

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   Discussion Top


Neuropathy in HSAN IV involves small-caliber (A-delta and C) nerve fibers which normally transmit nociceptive inputs along sensory nerves. Sensory testing of thermal and vibratory perception is abnormal and there is absence of sweating in response to sympathetic stimulation though autonomic perturbations are mild to absent. More than 37 different mutations in the neurotrophic tyrosine kinase receptor (NTRKA) gene, encoding a high-affinity NGF receptor, on chromosome 1q21-22 are described in HSAN IV. [4],[5]

The reported patient had severe anhidrosis, absence of pain sensation, and self-mutilating behavior [Figure 3], starting in infancy. Due to absent pain sensation, HSAN IV patients frequently develop extensive skin ulcers [Figure 2]. The absence of sweating makes the skin dry, hyperkeratotic and parchment-like further making it susceptible to recurrent, refractory infection. Osteomyelitis and recurrent bone fractures may lead to development of Charcot joints. In the present case, the left leg was amputated below knee and he also had non-healing fracture of right femur. Up to 43% mortality in such patients has been attributed to hyperpyrexia and sepsis combined. [4],[6] Inadequate response to stress might contribute to significant mortality, morbidity. [7] In our case, the patient developed fulminant septicemia due to extensive skin ulceration and died of DIC with uncontrolled bleeding.

Impairment of pain sensation and self-mutilation may also be seen in rare syndromes such as Lesch Nyhan syndrome and de Lange syndrome. In our patient, there was striking loss of pain perception and profound anhidrosis. There was no peripheral nerve thickening. These findings along with the absence of dysmorphic features, a normal serum uric acid level, electrophysiological studies and nerve biopsy histopathological findings of reduced small sympathetic myelinated and unmyelinated nerve fibers [Figure 1] confirmed the diagnosis of sensory autonomic neuropathy in our case.

Our patient did not have mental retardation on formal assessment, unlike typical cases of HSAN IV. [5] However, classical features of type IV HSAN, generalized loss of pain sensation, and profound anhidrosis were present. Therefore, our case could represent a unique variant of HSAN type IV without mental retardation. [2],[5] Due to lack of availability of genetic tests, mutational studies could not be done in our case. The present case history and clinical images illustrate that HSAN type IV, rarely seen in pediatric population, is one of the most debilitating neuropathies of childhood with a high morbidity and a shortened life span.


   Acknowledgments Top


We would like to acknowledge the Department of Pharmacology, SDM College of Medical Sciences and Hospital, for performing Bedside Sweat test and Department of Neuropathology, National Institute of Mental Health And NeuroSceinces, Bangalore for reporting the histopathological findings of Nerve Biopsy.

 
   References Top

1.Ishikiriyama S. Congenital insensitivity to pain with anhidrosis, Nishida syndrome. Ryoikibetsu Shokogun Shirizu 2000;30:288-90.  Back to cited text no. 1
[PUBMED]    
2.Suriu C, Khayat M, Weiler M, Kfir N, Cohen C, Zinger A, et al. Skoura - a genetic island for congenital insensitivity to pain and anhidrosis among Moroccan Jews, as determined by a novel mutation in the NTRK1 gene. Clin Genet 2009;75:230-6.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.Matsuo M, Kurokawa T, Goya N, Ohta M. Congenital insensitivity to pain with anhidrosis in a 2-month-old boy. Neurology 1981;31:1190-2.  Back to cited text no. 3
[PUBMED]    
4.Schwarzkopf R, Pinsk V, Weisel Y, Atar D, Gorzak Y. Clinical and genetic aspects of congenital insensitivity to pain with anhidrosis. Harefuah 2005;144:433-7.  Back to cited text no. 4
[PUBMED]    
5.Axelrod FB, Gold-von Simson G, Oddoux C. Hereditary Sensory and Autonomic Neuropathy IV. In: Pagon RA, Bird TC, Dolan CR, Stephens K, editors. GeneReviews [NCBI GeneTests Web site]. Seattle (WA); 2009 Nov 24. Available from: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=geneandpart=hsan4. [Last Accessed on 2010 Nov 2].  Back to cited text no. 5
    
6.Shorer Z, Moses SW, Hershkovitz E, Pinsk V, Levy J. Neurophysiologic studies in congenital insensitivity to pain and anhidrosis. Pediatr Neurol 2001;25:397-400.  Back to cited text no. 6
[PUBMED]  [FULLTEXT]  
7.Loewenthal N, Levy J, Schreiber R, Pinsk V, Perry Z, Shorer Z, et al. Nerve Growth Factor-Tyrosine kinase pathway is involved in thermoregulation and adaptation to stress: Studies on patients with Hereditary Sensory and Autonomic Neuropathy Type IV. Pediatr Res 2005;57:587-90.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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    Abstract
   Introduction
   Case Report
   Discussion
   Acknowledgments
    References
    Article Figures

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