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|Year : 2021 | Volume
| Issue : 4 | Page : 1021-1023
Cerebral Venous Sinus Thrombosis in a Child with Lesch–Nyhan Syndrome
Ranjith K Manokaran1, Prashant Jauhari1, Biswaroop Chakrabarty1, Neerja Gupta2, Atin Kumar3, Sheffali Gulati1
1 Child Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
2 Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radiodiagnosis, Jai Prakash Narayan Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||09-May-2017|
|Date of Decision||24-May-2019|
|Date of Acceptance||24-Jun-2019|
|Date of Web Publication||2-Sep-2021|
Child Neurology Division, Department of Pediatrics, Room No. 3056, Third Floor, Teaching Block, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
Lesch–Nyhan syndrome is a rare neurometabolic condition characterized by progressive choreoathetosis, intellectual disability, and peculiar manifestations like self-mutilation. Occasional case reports in adults have suggested an association between Lesch–Nyhan syndrome and hypercoagulability; however, no such report of either a venous or arterial stroke in children with Lesch–Nyhan Syndrome exists in literature. We present a 3-year-old boy with global developmental delay, dystonic posturing, choreoathetoid movements, and self-mutilation involving fingers and lips. He had acute worsening of sensorium, recurrent seizures, and opisthotonous posturing. A diagnosis of Lesch–Nyhan Syndrome was confirmed by extremely low hypoxanthine-guanine phosphoribosyltransferase enzyme levels. In view of an acute neurological deterioration, magnetic resonance imaging brain and magnetic resonance venogram were done that showed sagittal and left transverse venous sinus thrombosis. This case is the first case report of cerebral venous sinus thrombosis in a child with Lesch–Nyhan Syndrome. It further strengthens the association between hypercoagulability and Lesch–Nyhan syndrome.
Keywords: Choreoathetosis, dystonia, hypercoagulability, Lesch–Nyhan syndrome, self-mutilation, venous thrombosisKey Message: Lesch Nyhan syndrome is inherently a hypercoagulable state and may rarely present with venous thrombosis in children.
|How to cite this article:|
Manokaran RK, Jauhari P, Chakrabarty B, Gupta N, Kumar A, Gulati S. Cerebral Venous Sinus Thrombosis in a Child with Lesch–Nyhan Syndrome. Neurol India 2021;69:1021-3
Lesch–Nyhan syndrome is a rare neurometabolic condition characterized by progressive choreoathetosis, intellectual disability, and peculiar manifestations like self-mutilation. Many comorbid conditions such as epilepsy are associated with this disorder. Occasional case reports in adult patients have suggested an association between Lesch–Nyhan syndrome and hypercoagulability; however, no such report of either a venous or arterial stroke in children with Lesch–Nyhan Syndrome exists in literature. We report a child with Lesch–Nyhan syndrome who presented with a cerebral venous sinus thrombosis.
| » Case Report|| |
A 3-year-old boy presented to the emergency room with the complaints of recurrent seizures and episodes of abnormal twisting postures of the body for the last three days. There was history of global developmental delay, episodes of abnormal dystonic posturing, and choreoathetoid movements from infancy. Parents also gave a peculiar history of self-mutilation involving fingers and lips. Two other elder male siblings in the family had similar complaints and had succumbed to this illness in the past.
On examination, weight for age was 8 Kg (<3 standard deviation (SD)); height for age was 90 cm (<3 SD), suggestive of chronic malnutrition. Head circumference was 48 cm (between -3 SD to -2 SD). There was evidence of self-mutilation in the form of injuries involving lips and finger tips [Figure 1]. The child had altered sensorium with papilledema on fundus examination. There were frequent episodes of generalized dystonic posturing and choreoathetosis.
|Figure 1: Self-mutilation of lips (a) and fingers (b) in a child with Lesch–Nyhan syndrome|
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Baseline hematological and biochemical investigations were normal. Serum uric acid level was elevated 11 mg/dl (normal level – 3.4 to 7 mg/dl). Based on the clinical features and investigations, a diagnosis of Lesch–Nyhan syndrome was made, which was confirmed by extremely low hypoxanthine-guanine phosphoribosyltransferase enzyme levels (<1% of the normal activity). In view of worsening encephalopathy, seizures and presence of papilledema, magnetic resonance imaging brain and magnetic resonance venogram were done that showed sagittal and left transverse venous sinus thrombosis [Figure 2]. Stroke workup which includes echocardiogram, serum homocysteine, protein C, protein S, antithrombin III level, factor V Leiden mutation, and prothrombin mutation did not reveal any abnormality. The child was started on supportive measures to reduce intracranial hypertension and subcutaneous low molecular weight heparin. He was put on allopurinol for stabilization of serum uric acid levels; trihexiphendyl for dystonia and tizanidine for control of spasticity. A soft fabricated mouth guard was provided for prevention of perioral injury. The child showed improvement in the level of alertness with cessation of seizures and resolution of dystonic posturing.
|Figure 2: Magnetic resonance venography of the child with Lesch–Nyhan syndrome showing filling defect suggestive of sagittal and left transverse venous sinus thrombosis|
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| » Discussion|| |
Lesch–Nyhan Syndrome is an X-linked defect of purine metabolism. The syndrome results from an inborn error of metabolism resulting from a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase. It results in marked overproduction of uric acid and consequent hyperuricemia, gout, urate nephropathy, and neurologic symptoms. Self-injurious behavior in a child with developmental delay should prompt the clinicians to look for the features of Lesch–Nyhan Syndrome. Imamura et al. reported patients with Lesch–Nyhan Syndrome in which there was a hypercoagulable state. Epidemiologic studies have shown an association between high levels of uric acid and cardiovascular thrombosis., Riaz et al. reported a patient with Lesch–Nyhan syndrome with recurrent myocardial infarctions, thromboembolic disease, and thrombus formation in bronchi despite antithrombotic therapy. All these cases were reported in adults. No such report in children is available.
Hypercoagulability is a major risk factor for venous sinus thrombosis in children. Lesch–Nyhan syndrome is an extremely rare cause of hypercoagulablility and therefore it is seldom included in the list of hypercoagulable states. Hypercoagulability in Lesch–Nyhan syndrome could be multifactorial; however, the exact mechanism is poorly understood. High levels of fibrinopeptide A, beta-thromboglobulin, platelet factor 4, and low levels of 6-keto prostaglandin F1 alpha have been implicated as a cause for hypercoagulability in adults with Lesch–Nyhan syndrome., The role of hyperuricemia in hypercoagulability is also unknown. We hypothesize that a similar mechanism for hypercoagulability can exist in children and could have led to venous thrombosis in the index case. Due to limited knowledge and the rarity of the condition, there are no recommendations regarding the need for prophylaxis as well as the duration and choice of anticoagulant therapy in this syndrome. Nevertheless, this association should prompt clinicians to consider arterial or venous thrombosis in children with Lesch–Nyhan syndrome who present with a cerebrovascular event. To conclude, this case is the first case report of cerebral venous sinus thrombosis in a child with Lesch–Nyhan Syndrome. It further strengthens the association between a hypercoagulability and Lesch–Nyhan syndrome.
We acknowledge Dr Priyanka Madaan, Dr Vivek Sirolia, and Dr Ketan Kumar for their contribution in the patient care. We thank the patient's family for their participation and consent in this case report.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]