Lesch-Nyhan Syndrome in an Indian Child.

Hypoxanthine guanine phosphoribosyl transferase-1 (HGPRT-1) leading to Lesch-Nyhan syndrome (LNS) is one of the important causes of self-mutilation. Hereby, we report a case of LNS in a three and half-year-old male child, who presented with characteristic self-mutilating behavior. He had history of developmental delay, difficulty in social interaction, attention deficit and features of autism. His serum blood biochemistry was normal except for low hemoglobin levels and raised serum uric acid levels. With a diagnosis of LNS, the child was treated with allopurinol. With various modalities of physical restraint, his self-mutilating behavior came under control and currently the patient is being followed up.

What was known?

Lesch-Nyhan syndrome (LNS) is an X-linked recessive inborn error of purine metabolism associated with uric acid overproduction

It is associated with self mutilation.

Introduction

Lesch-Nyhan syndrome (LNS) is an X-linked recessive inborn error of purine metabolism associated with uric acid overproduction.[1] Thus, the disease process mainly affects the male child and women are asymptomatic carriers. Increased plasma uric acid levels damages the basal ganglia leading to cognitive disturbances, neurologic dysfunction and self-mutilating behavior.[2] Neurological manifestations include severe action dystonia, choreo-athetosis, ballismus, cognitive and attention deficit, and self-destructive behavior. Serum hyperuricemia can lead to crystal-induced gouty arthritis, while hyperuricosuria can manifest as nephrolithiasis in later stages of life.[3] Usually LNS is present at the time of birth in a male child, but complications like delayed developmental milestones may present during the first year of life. Self-mutilating behavior along with repetitive movements of both the limbs usually appears around 2 years of age.[4] HGPRT deficiency may cause megaloblastic anemia due to body's inability to utilize vitamin B12.

Case Report

A three and half year old male child was brought by his parents for seeking consultation for his skin problems. Parents reported that the child was scratching and damaging his various body parts since the age of 2 years. The child incessantly kept scratching his skin even during sleep to produce deeper abrasions and ulcerations. Parents denied any history of any itchy skin disease in other close family members. Cutaneous examination showed deep ulcers with secondary infection over dorsum of feet and hands, ears, nape of neck and thighs ranging in size from 2 to 6 cm [Figures 1 and 2]. These ulcers were present only over the areas which were easily accessible for scratching. There was no focus of any parasitic infestation or features suggestive of atopic eczema. A pediatric and psychiatric opinion was sought for his abnormal behavior. His detailed systemic evaluation revealed delayed developmental milestones, difficulty in social interaction, head banging and aggression along with attention deficit making him a school dropout.

Figure 1

Deep erosions and ulcers present on various body parts due to self-mutilation

Figure 2

Deep erosions and ulcers present on various body parts due to self-mutilation

His routine blood biochemistry was normal except for low hemoglobin level (8.1 g/dl) and higher normal uric acid level (9.48 mg/dl). The child was treated with broad spectrum antibiotic (syrup amoxicillin trihydrate/potassium-clavulanate; 125 mg/5 ml) three times daily for infected ulcers along with regular dressings. The child was prescribed oral allopurinol (4 mg/kg) to suppress uric acid production. To prevent further self-mutilation, parents were taught various techniques of physical restraints (elbow guard, dental guard, etc).

Discussion

The diagnosis of LNS is based on clinical and biochemical findings (hyperuricemia and hyperuricosuria), together with psychomotor delay and enzymatic (determination of HGPRT activity in red blood cells or fibroblasts) and molecular tests. HGPRT deficiency leads to characteristic triad of features: (i) hyperuricemia, (ii) spectrum of neurological dysfunctions and (iii) cognitive and behavioral disturbances.[5] One of the early clues of disease may be the observation of orange crystals in the diapers of a newborn. Hyperuricemia may lead to formation of crystals of uric acid in the renal system which may be passed in the urine.[6] Precipitation of urate crystals in the urinary tract may lead to obstructive uropathy and resultant repeated bouts of urinary tract infections. Similar process can occur in the joints leading to gouty arthritis.[7] Torres and Puig have proposed a classification system into four groups depending upon clinical, biochemical, enzymatic and molecular analysis [Table 1].

Table 1

Classification of HGPRT deficiency based on clinical, biochemical, enzymatic and molecular data

Self-injurious behavior is also present in other conditions such as idiopathic mental retardation, autism, Tourette syndrome and Cornelia de Lange syndrome. Hypotonia is a common feature which may render the child non-ambulatory. Involuntary muscle activity such as choreoathetosis and ballismus are usually present but are not evident at rest. Child exhibits the characteristic self-mutilating behavior after attaining 2 years of age.

The definitive diagnosis of LNS is primarily based on activity of HGPRT enzyme which is decreased in the cells from all the tissues of the body. Prenatal diagnosis for LNS can be performed with amniotic cells obtained by amniocentesis at about 15–18 weeks’ gestation, or chorionic villus biopsy obtained at about 10–12 weeks’ gestation.[8]

Allopurinol treatment reduces the over production levels of uric acid. Self-injurious behavior can be managed with a various combination of physical restraints, behavioral and pharmacological treatment. Stress and anxiety attacks trigger violent self-mutilating behavior. A sedative agent like benzodiazepines reduces the anxiety and stress. However, the main stay of treatment to prevent patient from injuring themselves is physical restraints. A pair of gloves can be provided to prevent finger biting. A dental guard aims to prevent cheek biting and biting off other body parts.

What is new?

Diagnosis is difficult in resource poor settings

Management is multidisciplinary and life long

Social rehabilitation can be challenging.