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Dopamine Beta-Hydroxylase Deficiency

Background
Who should be tested?
Testing Methodology
Potential Outcomes & Interpretation of Test Results
Cautions
For More Information

Background

Dopamine beta-Hydroxylase deficiency (DBHD) is a rare autosomal recessive form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. DBH deficiency is mainly characterized by impaired exercise intolerance, severe orthostatic hypotension and persistent ptosis. These findings generally worsen in late adolescence and early adulthood.

DBHD is caused by a mutation in the DBH gene, located on chromosome 9 (9q34). Dopamine beta-hydroxylase is a copper-containg enzyme important in the synthesis of catecholamines, namely the conversion of dopamine to norepinephrine. Biochemical findings in individuals with DBHD include complete absence of plasma norepinephrine and epinephrine in conjunction with elevated plasma dopamine levels.

DBHD occurs when an individual receives two copies of a defective gene, one from each parent. Any person with one copy of the defective DBH gene is a carrier. Carriers do not have DBHD and will not develop the disease. However, if their partner is also a carrier, there is a one in four chance (25%) that their baby will be born with DBHD. There is a three in four chance (75%) that their baby will not have DBHD.

Who should be tested

• Patients with clinical symptoms of dopamine beta-hydroxylase deficiency
• Patients with biochemical findings consistent with dopamine beta-hydroxylase deficiency
• Relatives of individuals affected with dopamine beta-hydroxylase deficiency
• At-risk relatives with a known familial DBHD mutation identified

Testing Methodology

Direct Mutation Analysis: All samples are analyzed by direct sequence analysis of the 12 exons of the DBH gene.

Sensitivity of the Test: 50-100% of all DBH mutations can be detected by molecular analysis.

Potential Outcomes & Interpretation of Test Results

Cautions

• Test results should be interpreted in the context of clinical findings, family history, and other laboratory data.
• Biochemical testing for plasma norepinephrine and dopamine is advised in addition to molecular analysis.
• This test was developed and its performance characteristics validated by the Molecular Genetics Laboratory at the Hospital for Sick Children. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. This test is used for clinical purposes.

For More Information

• Online Mendelian Inheritance in Man - Item # 223360
• GeneReviews online clinical information resource
  • funded by the U.S. National Institutes of Health, Developed at the University of Washington, Seattle.
• Timmers HJLM et al (2004). Congenital Dopamine-B-Hydroxylase Deficiency in Humans. Ann. N.Y.Acad.Sci. 1018: 520-523.
• Garland EM et al (2002). Genetic Basis of Clinical Catecholamine Disorders. Ann. N.Y.Acad.Sci. 971: 506-514.