A New Tyrosine Hydroxylase Genotype Associated With Early-Onset Severe Encephalopathy

• Published in: Journal of Child Neurology Vol. 27; no. 4; pp. 523 - 525
• Main Authors: Giovanniello, Teresa, Claps, Dianella, Carducci, Carla, Carducci, Claudia, Blau, Nenad, Vigevano, Federico, Antonozzi, Italo, Leuzzi, Vincenzo
• Format: Book Review Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-04-2012
• Subjects: Age; Bioinformatics; Blood; Cerebrospinal fluid; Child, Preschool; Dystonia - blood; Dystonia - cerebrospinal fluid; Dystonia - complications; Dystonia - genetics; Encephalopathy; Genetic analysis; Genetic Testing; Genotypes; homovanillic acid; Homovanillic Acid - cerebrospinal fluid; Humans; Limbs; Male; Missense mutation; Mutation, Missense - genetics; Posture; Prolactin; Prolactin - blood; Psychomotor Disorders - blood; Psychomotor Disorders - cerebrospinal fluid; Psychomotor Disorders - complications; Psychomotor Disorders - genetics; Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - deficiency; Tyrosine 3-Monooxygenase - genetics; biogenic amine disorders; autosomal recessive dopa-responsive dystonia; tyrosine hydroxylase deficiency; early-onset encephalopathy
• ISSN: 0883-0738; 1708-8283
• DOI: 10.1177/0883073811420717

We describe a boy affected by an early-onset severe encephalopathy (stagnation of psychomotor development, paroxysmal dystonic postures and movements of limbs, hypokinesia) due to tyrosine hydroxylase deficiency. High blood prolactin and low homovanillic acid in cerebrospinal fluid suggested the diagnosis. Genetic analysis revealed 3 new missense mutations on tyrosine hydroxylase gene: [c.752C>T(p.P251L) and c.887G>A(p.R296Q] harbored by the father and c.836G>T (p.C279F) of maternal origin. Bioinformatics tools have been helpful in predicting the pathogenic role of p.P251L and p.C279F substitutions, while a weak pathogenic effect was ascribed to p.R296Q.