Lesch-Nyhan syndrome. A case report

[Downloaded free from http://www.jisppd.com on Wednesday, June 26, 2013, IP: 117.220.36.235]  ||  Click here to download free Android application for this journal

ISSN 0970 - 4388

Lesch-Nyhan syndrome: A case report KALE A.a, SHAH K.b, HALLIKERIMATH S.c

Abstract Lesch-Nyhan syndrome, a rare inborn error of metabolism, is characterized by mental retardation and self-destructive behavior resulting in self-mutilation through biting and scratching. It is a rare anomaly consisting of deficiency in the production of hypoxanthine phosphoribosyltransferase that leads to the overproduction of purine and accumulation of uric acid. No medical treatment exists to alleviate the symptoms of self-mutilation where direct dental intervention is the only way these behavior can be affected. A unique case of this type affecting a 6-year-old male child is reported. Keywords: Lesch- Nyhan syndrome, uric accid, amputation

Perioral self-mutilating behavior is thought to begin with the eruption of teeth; patients then begin to bite themselves. The behavior continues and results in partial or total destruction of perioral tissue especially the lower lip. Partial or complete amputation of fingers, toes, and tongue is also common. Life expectancy is reduced. Most patients die in childhood and survival up to 20 years of age is known but rare.[3,4]

Introduction Lesch-Nyhan syndrome (LNS) first described in 1964,[1] is clinically characterized by mental retardation, choreoathetosis, spastic cerebral palsy, and aggressive self-mutilating behavior. It is a rare X-linked recessive disorder of purine metabolism, which is caused by abnormal gene on the X chromosome. Its expression is fully recessive with a severe deficiency of the enzyme hypoxanthine guanine phosphoribosyltransferase (HGPRT).[2] This deficiency gives rise to excessive uric acid production and consequent hyperuricemia [Figure 1]. Affected males with this incurable disease are mentally and physically retarded and suffer from spasticity, choreoathetosis, hyperuricemia, and cerebral palsy. A consistent presentation in all cases of LNS is the abnormal, compulsion toward selfmutilation usually reported after 1 year of age.[3-5]

Various forms of treatment have been instituted in an attempt to curb the destructive pattern of behavior. Currently, there is no cure for the syndrome; prevention is, therefore, the standard of care. Over the years many inventive and effective approaches involving an assortment of hand restraints, dental mouth guards, and dental extractions have been utilized.[3,4,6-8]

Materials and Methods A 6-year-old male child was referred to the Institute of Dental Sciences, KLE University, Belgaum, by an Orthopedic surgeon for evaluation and treatment of lip lacerations associated with self-mutilating behavior [Figure 2]. The parents reported that from infancy the child had been very quite and did not elicit response to many stimuli, though cerebral palsy and mental retardation was not noted. The condition remained until the age of 2 years when he aggressively started biting his thumb and figures of the hand. The child was taken to the Orthopedic surgeon as parents noted fragmented pieces of bone piercing out of the skin of the left leg after about 20 days of history of fall, though the child had no complain of pain [Figure 1]. Radiograph revealed a compound fracture. After treatment for the same the child was referred to the Institute.

Figure 1: Biochemical pathway involved in uric acid production

On examination it was observed that the child’s hand and feet were rapped with cloth. After removal of the cloth all the fingers of both hands were found to be missing. In some areas raw wound and necrosis was evident. The patient had chewed most of the fingers leaving a small stump of 1-2 cm

a Professor and Head, Department of Oral and Maxillofacial Pathology, b,cTeaching Faculty, KLE Dental College and Hospital, Belgaum, Karnataka, India

S11

J Indian Soc Pedod Prevent Dent - Supplement 2008

[Downloaded free from http://www.jisppd.com on Wednesday, June 26, 2013, IP: 117.220.36.235]  ||  Click here to download free Android application for this journal

Fluoride reduction by water purification system

Figure 2: Laceration of lower lip due to self-mutilation behavior

Figure 5: Self-mutilation of fingers of right hand

Figure 3: Compound fracture of left leg with discharging wound

Figure 6: Self-mutilation of right leg

Figure 4: Self-mutilation of fingers of left hand

Figure 7: Necrosed left leg

J Indian Soc Pedod Prevent Dent - Supplement 2008

S12

[Downloaded free from http://www.jisppd.com on Wednesday, June 26, 2013, IP: 117.220.36.235]  ||  Click here to download free Android application for this journal

Fluoride reduction by water purification system

[Figures 3 and 4]. He had even chewed all his toes of his right foot and the big toe of the left foot [Figures 5 and 6]. The Orthopedic surgeon had planned partial amputation of the left foot due to infection, necrosis, and gangrene [Figure 7].

disorder, there have been a few reported cases involving female patients.[6] In summary, the specific relationship between neurologic symptoms associated with LNS is unclear. Treatment consists of allopurinol to protect kidney function and dental extractions for self-protection.

Extraoral examination revealed that the lower lip was missing and the tissues were lacerated [Figure 2]. The parents informed that few milk teeth were extracted a year back by local dentist. The child was then referred to the Department of Pediatric Dentistry for needful. Patient was referred to the physician and after multiple neurologic and serologic assays the child was diagnosed with LNS. The patient was treated for the lacerations on the lip. The maxillary and mandibular permanent central incisors, which were the only anterior teeth present, were extracted.

References 1. 2.

3.

4.

Discussion 5.

Lesch-Nyhan syndrome was first reported in two brothers, 4 years apart in age by Lesch and Nyhan in 1964,[1] since then many cases have been identified in many races throughout the world. Nyhan has stated that next to phenylketonuria, LNS is the second most common inborn metabolic disorder.[1,5] Pregnancy and postpartem deliveries of LNS patients typically have been reported to be normal.[3] Prenatal diagnosis of the amount of HGPRT enzyme deficiency becomes important in view of severe handicap seen in affected males.[10,11]

6. 7.

8.

9.

In pediatric patients, self-mutilation is seen in genetic syndromes such as LNS, Cornelia de Lange, Gilles de la Tourette syndrome,[1,8,12] mental retardation,[8,13] infectious disease such as encephalitis,[8,14] congenital malformation.[8,15] A careful evaluation is, therefore, essential toward making the appropriate diagnosis of LNS. Since the discovery of LNS, however, there have been few significant advances in its medical and behavioral management. Several of the management problems require a choice between extraction of teeth rather than using the dental appliance.

10.

11.

12. 13. 14.

15.

The aggressive behavior usually wanes in patients older than 10-12 years of age. Patients with LNS usually die in their late second or third decade. Cause of death is renal failure or infections that are a result of decrease in lymphocyte and IgG levels. Although LNS syndrome is an X-linked recessive

Lesch M, Nyhan WL. A similar disorder of uric acid metabolism and central nervous system function. Am J Med 1964;36:561-70. Seegmiller JE, Rosenbloom FM, Kelly WN. Enzyme defect associated with a sex linked human neurological disorder and excessive purine synthesis. Science 1967;155:1682-4. Christie R, Bay C, Kaufman JA, et al. Lesch nyhan disease: Clinical experience with nineteen patients. Dev Med Child Neurol 1982;24:293-306. Evans J, Sirikumara M, Gregory M. Lesch Nyhan Syndrome and the lower lip guard. Oral Surg Oral Med Oral Pathol 1993;76: 437-40. Dicks JL. Lesch Nyhan syndrome: A treatment planning dilemma. Pediatr Dent 1982;4:127-30. Smith BM, Cutilli BJ, Fedele M. Syndrome: A case report. Oral Surg Oral Med Oral Pathol 1994;78:317-8. Sugahara T, Mishima K, Mori Y. Lesch Nyhan Syndrome: Successful prevention of lower lip ulceration caused by self mutilation by use of a mouth guard. Int J Oral Maxillofac Surg 1994;23:37-8. Chen LR, Liu JF. Successful treatment of self inflicted oral mutilation using an acrylic splint retained by a head gear. Pediatr Dent 1996;18:408-10. Cusumano FJ, Penna KJ, Panossian G. Prevention of self mutilation in patients with Lesch Nyhan Syndrome: Review of literature. J Child Dent 2001;175-8. Zoref Shani E, Bromberg Y, Goldman B. Prenatal diagnosis of Lesch Nyhan Syndrome experience with three fetuses at risk. Prenat Diagn 1989;9:657-61. Graham GW, Aitken DA, Connor JM. Prenatal diagnosis by enzyme analysis in 15 pregnancies at risk for the Lesch-Nyhan Syndrome. Prenat Diagn 1996;16:647-51. Cataldo MF, Harris JC. The biologic basis of self-injury in mentally retarded. Anal Interv Dev Disabil 1982;2:21-39. Corbett J. Aversion for the treatment of self injurious behaviour. J Ment Defic Res 1975;192:79-95. Finger ST, Duperon DF. The management of self inflicting oral trauma secondary to encephalitis: A clinical report. J Dent Child 1991;58:60-3. Hyman SL, Fisher W, Mercugliano M, Cataldo MF. Children with self-injurious behavior. Pediatrics 1990;85:437-41.

Reprint requests to: Dr. Alka Kale KLE Dental College and Hospital, Belgaum, Karnataka, India

S13

J Indian Soc Pedod Prevent Dent - Supplement 2008