6-pyruvoyl-tetrahydropterin synthase deficiency: the clinical spectrum in 3 Chinese patients

Abstract

OBJECTIVES: To describe the clinical characteristics of 3 patient with 6-pyruvoyltetrahydropterin synthase (PTPS) deficiency. METHODS: The medical notes of these patients were reviewed. The clinical and the biochemical features were described. RESULTS: The first two patients presented at 5 to 6 months old with episodes of prolonged eye staring and stiffening of the 4 limbs which lasted for 30 minutes to 1 hour. These could happen few times per week. They had global delay. The third patient, who was 19 years old, had an initial diagnosis of dyskinetic cerebral palsy, epilepsy and mental retardation. Physical examination revealed a fair skin complexion. There was intermittent dystonia and choreoathetosis involving all the 4 limbs. Blood for amino acid in these patients showed hyperphenylalanaemia. Tetrahydrobiopterin (BH4) loading showed complete normalization of plasma phenylalanine. Urine pterins showed decreased biopterin with normal to high neopterin. Cerebrospinal fluid analysis was low for biogenic amines including 5-hydroxyindoleacetic acid and homovanillic acid. All of them were diagnosed to have PTPS deficiency. 2 of them were confirmed by genetic testing and the result was pending for the third one. The first 2 patients' clinical symptoms and signs responded well to replacement of BH4, l-dopa and 5-hydroxytryptophan. The third patient was about to be started on treatment. CONCLUSION: In places without newborn screening for inborn error of metabolism like Hong Kong, early recognition of this potentially treatable neurological condition is crucial to improve the associated neurological morbidity.