Congenital Insensitivity of Pain with Anhidrosis Bhaskar G u p t a

Neonatal Intensive Care Unit, Khoula Hospital, Muscat, Sultanate of Oman.

Abstract, Congenital insensitivity to pain with anhidrosis is an autosomal recessive disorder included in a group of rare diseases termed as hereditary sensory-motor neuropathies. The diagnosis is made usualtyin early childhood period as most of the children present with recurrent unexplained hyperpyrexia. This case report is of a neonate who presented with tachypnea and fever on second day of life being treated for clinical sepsis and had no response to antibiotics. On pricking for IV canulation there was no cry, and temperature of the baby returned to normal on removing the covering blankets. Diagnosis was established by family history, skin and sural nerve biopsy. Early diagnosis is important for prevention of injury, self mutilation and growth retardation. This case report points to the question that should assessment of pain sensation be a part of routine examination of newborn. [Indian J Pediatr 2003; 70 (1) : 109-111]

Key words : Insensitivity; Anhidrosis; Hyperpyrexia

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder with features of congenital analgesia which leads to self mutilation, inability to sweat leading to defective thermoregulat ion and episodes of recurrent unexplained fever, and mental retardation. 1,2 Sensation to touch is intact and lacrimation is normal. 4 This r e p o r t is of neona t e w i th man i fe s t a t ions of congential insensi t ivi ty to pain with anhidrosis who p r e s e n t e d wi th pe r s i s t en t fever and d iagnosis was established by family history, clinical examination, skin and nerve biopsy.

Awareness of the parents about this condition in order to avoid excessive wrapping, prevention of dehydration and measures to reduce hyperpyrexia are essential to r e d u c e the mor t a l i t y in such babies. L o n g - t e r m complications like fractures, bony deformities, recurrent b u r n s and w o u n d s , denta l and eye in jur ies can be prevented by early diagnosis and appropriate medical and educational care.

CASE REPORT

A fuU-term appropriate for gestational age male baby was born by Spontaneous Vaginal delivery at a tertiary care center in Muscat , Sultanate of Oman to 25 years old Gravida 3, Para 2, mother with i living male child now 3 years old. There is history of consanguinity and previous sibling affected with same disorder. Baby was found to have poor act ivi ty , d i f f icul ty in feeding, fever and tachypnea on second day of life. A full septic work up was done wh ich d id no t revea l any ev idence of

Reprint requests : Dr. Bhaskar Gupta, Neonatal Intensive Care Unit, Khoula Hospital, Post Box No 90, Post code 116. Muscat, Sultanate of Oman. Fax : 00968 - 561445. E-mail : brg30363@omantet.net.om

septicemia. Baby was kept on antibiotics but persisted to have fever. While collecting blood samples and doing procedures like I.V. canulation and lumbar puncture and

Fig. 1. 3-year-old previous child with normal facies, normal lacrimation, recurrent fractures with bony deformity of right forearm and self mutilation of digits.

Indian Journal of Pediatrics, Volume 70--January, 2003 109

Bhaskar Gupta

suprapubic aspiration, it was noticed that the baby did not have response to pain and did not cry.

Skin biopsy of this baby showed normal epidermis and dermis and presence of sweat glands. Results of electromyography was normal, and nerve conduction studies of median nerve showed a normal motor and sensory nerve conduction. Application of pilocarpine showed anhidrosis.

Sural Nerve biopsy revealed markedly reduced numbers of unmyelinated and small myelinted fibres, all these findings consistent with congenital insensitivity to pain with anhidrosis.

Antibiotics were discontinued and the mother was instructed not to wrap the baby excessively and prevent the baby from trauma. Further evaluation of the family history revealed that the previous sibling who is now 3 years old also had recurrent episodes of fever requiring admissions, insensitivity to pain, anhidrosis, recurrent fractures, shortening and bowing of right forearm due to improper healing of fractures, self mutilation and auto amputation of fingers, dental anomalies and normal facies ( Fig. 1) and poorly healing ulcers over the forearm (Fig. 2).

Fig. 2. Recurrent poorly healing ulcers due to burn injury on forearm in the same child.

DISCUSSION

Congenital insensitivity to pain with anhidrosis is one of a group of rare diseases termed hereditary sensory motor neuropathies often labeled as Type IV. This disorder is characterized by congenital insensit ivity to pain, anhidrosis and this results in recurrent hyperpyrexia and self mutilation, there are recurrent infections, chronic osteomyelitis, bone and joint deformities and sometimes even limb amputations. ~ Most of the children present in early childhood with deep ulceration on knees, elbows and scars from recurrent burns at various sites. 3 All these children's have self inflicted injuries varying from skin ulcers, burns and bone fractures to auto amputations of fingertips and tongue. 4

Death from h ~ i a within first 3 years of life may occur in 20% c a m if not managed properly. 5 Besides the rarity of these clinical entities, difficulty in evaluating the sensory disturbances in neonates delays the d iagno~. Moderate mental retardation is reported frequently in most of tl~ caaes. 6~ History of consanguinity is common and so ~ ~ may provide a clue to the diagnosis.

Diagnosis is established by normal electromyography and nerve conduction studies skin biopsy showing microscopically normal sweat glands, pi locarpine application showing anhidrosis, and nerve b iopsy showing markedly reduced numbers of unmyelinated and small myelinated fibers. 6,7

Besides the m u l ~ involvement in this condition, there is s low healing of wounds , immunological abnormalities such as low response to specific stimuli 8 and in some cases chronic inflammatory state ending in systemic amyloidosis. 9'~~ Absent corneal sensation and corneal ulcers that heal poorly has been observed. ~~ Injury to the tongue and oral mucosa due to sharp erupting tooth may occur, n

Human NTRK1 gene encodes the receptor tyrosine kinase for nerve growth factor and is the gene responsible for congenital insensitivity to pain with anhidrosis. 8 A review of 28 Israeli Bedouin patients showed high degree of consanguinity and TrkA gene which encodes the receptor for nerve growth factor. 2 new mutations were identified in the tyrosine kinase domain for the TrkA gene which were 1926-ins-T and Pro-689-Leu mutation. In eight cases prenatal diagnosis was made by linakge analysis. 12 This case which presented with hyperpyrexia and family history of affected previous sibling with consistent features on nerve biopsy aided in early diagnosis. These patients need extreme care for prevention of injuries and burns, fractures, self mutilation and corneal ulceration. Regular fol low up and appropriate medical and educational care is needed for a proper growth and development of such babies. Parents should be explained to avoid measures like excessive wrapping, prevention of dehydration, and measure to reduce hyperpyrexia as lots of deaths can be prevented by these simple measures. Treating pediatrician should be made aware of the diagnosis in cases of hyperpyrexia in order to avoid unnecessary use of antibiotics and investigations, and will aid prompt institution of therapy to relieve hypothermia.

CONCLUSION

Early diagnosis, prevention and prompt treatment of hyperpyrexial episodes, protecting from burn and other injuries, application of protective splint on eruption of permanent sharp teeth, eye care to prevent corneal ulcers forms the cornerstone of management of such children's. Being a rare disorder, a posit ive family history or unexplained hyperpyrexial expisode in the neonatal

110 Indian Journal of Pediatrics, Volume 70--January, 2003

Congenital Immnaltlvity of Pain with Anhidroals

p e r i o d m a y g ive a c lue to the d iagnos i s . P rena ta l d i agnos i s c an be m a d e in affected famil ies b y

gene t ic l i nakge ana ly s i s ? 2

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