The Effect of S-Adenosylmethionine Treatment on Neurobehavioral Phenotypes in Lesch-Nyhan Disease

case reports in neurology
02 Dec, 2019 ,

A 6-month-old boy with LND was presented with generalized dystonia and self-injury behavior that was alleviated after receiving S-adenosylmethionine (SAMe). His self-injury behavior completely resolved after he received SAMe and risperidone. Although he had often experienced inspiratory stridor because of laryngeal dystonia and frequently developed aspiration pneumonitis and bronchitis, no inspiratory stridor was noted after SAMe treatment. The patient is continuing to receive SAMe and risperidone. SAMe treatment alleviates dystonic movements and improves quality of life in pediatric patients with LND. Additional research is needed to determine the long-term safety and efficacy of SAMe and its appropriate dosage.

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A 6-month-old boy presented to our institution with a 3-month history of motor development delay. He was the second child of healthy nonconsanguineous parents. The pre- and neonatal periods were uneventful. At admission, his height, weight, and head circumference were 68.8 cm (–0.8 standard deviation [SD]), 7.8 kg (–0.5 SD), and 44.8 cm (+0.7 SD). By 6 months, his head control was poor, and he had abnormal dystonic movements, ballismus, and extensor spasms with marked hypotonia.

The patient developed hyperuricemia (uric acid [UA], 10.3 mg/dL) and increased urinary UA (urinary UA/creatinine ratio, 5.3 [control range <2.0]). Cerebrospinal fluid monoamine and related metabolite analyses were unremarkable (pyridoxal phosphate, 62.3 nmol/L; pyridoxal, 58.0 nmol/L; 5-methyltetrahydrofolate, 61.0 nmol/L; homovanillic acid, 364.5 nmol/L; 5-hydroxyindole acetic acid, 273.7 nmol/L; 3-O-methyldopa, 50.7 nmol/L). Brain magnetic resonance imaging (MRI) showed no signs of cortical atrophy or abnormal intensities.

His electroencephalogram was normal and his development quotient on the Enjoji Scale of Infant Analytical Development was 42 at 8 months of age. His blood T cells were HPRT negative because they were 6-thioguanine resistant. The genetic analysis of his HPRT gene revealed the hemizygous g.151C>T (p. R51X) mutation, and we diagnosed the patient with classic LND. We administered allopurinol (up to 20 mg/kg/day) and added potassium citrate and sodium citrate when he was 15 months old. We added gabapentin (up to 40 mg/kg/day) for increased self-injury behavior at the age of 19 months and introduced SAMe treatment (up to 20 mg/kg/day) at the age of 23 months because his self-injury persisted.

Although the patient had persistent paroxysmal inspiratory stridor resulting from abnormal laryngeal movement and frequent hospitalizations for bronchitis or bronchopneumonia before SAMe treatment, his laryngeal stridor resolved 6 months after SAMe treatment, and he has had few episodes of bronchitis or pneumonia since. MRI performed when he was 26 months old revealed no atrophy or abnormal brain intensities (including the basal ganglia. His (previously resolved) lower lip biting recurred when he was 34 months old. We administered risperidone (up to 0.05 mg/kg/day), and the patient's self-injury behavior completely resolved owing to the combination therapy of SAMe and risperidone. At this time, he is 4 years old and can move short distances by rolling.