Tyrosine hydroxylase deficiency: Clinical manifestations of catecholamine insufficiency in infancy

• Published in: Movement disorders Vol. 17; no. 2; pp. 354 - 359
• Main Authors: Grattan-Smith, Padraic J., Wevers, Ron A., Steenbergen-Spanjers, Gerry C., Fung, Victor S.C., Earl, John, Wilcken, Bridget
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.03.2002; Wiley
• Subjects: Biological and medical sciences; Consanguinity; Developmental Disabilities - drug therapy; Developmental Disabilities - enzymology; Developmental Disabilities - genetics; dopamine; Dopamine - deficiency; Dopamine - genetics; epinepherine deficiency syndrome; Errors of metabolism; Female; Follow-Up Studies; Humans; Infant; infantile Parkinsonism; L-dopa induced dyskinesia; Levodopa - administration & dosage; Levodopa - adverse effects; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurologic Examination - drug effects; Neurology; Norepinephrine - deficiency; Norepinephrine - genetics; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - enzymology; Parkinsonian Disorders - genetics; Tremor - drug therapy; Tremor - enzymology; Tremor - genetics; Tyrosine 3-Monooxygenase - deficiency; Tyrosine 3-Monooxygenase - genetics; tyrosine hydroxylase deficiency; Human; Nervous system diseases; Pathophysiology; Tremor; Enzyme; Deficiency; Metabolic diseases; Tyrosine 3-monooxygenase; Video recording; Involuntary movement; Case study; Parkinsonism; Symptomatology; Chemotherapy; Treatment; Oxidoreductases; Levodopa; Neurological disorder; Child
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.10095

Inborn errors of catecholamine biosynthesis are rare but of great interest as they are genetic disorders, and in some, treatment may completely reverse severe neurological abnormalities. They also provide insights into the action of the biogenic amines in the developing brain. We describe the clinical course of an infant with tyrosine hydroxylase (TOH) deficiency over a 30‐month period. The parents are consanguineous, and genetic analysis revealed the infant to be homozygous for the common G698A mutation in the TOH gene. TOH deficiency can be seen as a model of pure catecholamine deficiency. Experimental evidence, reports of other disorders of biogenic amines, and our experience with this infant suggest that the symptoms of catecholamine deficiency in infancy can be broadly subdivided. Signs of dopamine deficiency include tremor, hypersensitivity to levadopa (L‐dopa) therapy, oculogyric crises, akinesia, rigidity, and dystonia. Manifestations of norepinephrine deficiency include ptosis, miosis, profuse oropharyngeal secretions, and postural hypotension. Hypersensitivity to L‐dopa was a particular management problem in this infant. © 2002 Movement Disorder Society.