Clinical Guidance

There are no known genotype-phenotype correlations.

Source: GeneReviews — "Dopamine Beta-Hydroxylase Deficiency"

Diagnostic Criteria

No consensus clinical diagnostic criteria have been published for dopamine beta-hydroxylase (DBH) deficiency. A clinical assessment including orthostatic vital signs and an ophthalmic exam should be the initial step; if indicated, this should be followed by autonomic function testing and plasma catecholamine analysis.

Suggestive Findings

DBH deficiency should be suspected in individuals with the following clinical, physiologic, and laboratory findings .

Clinical findings

Source: GeneReviews — "Dopamine Beta-Hydroxylase Deficiency"

Differential Diagnosis

The combination of minimal or absent plasma norepinephrine and epinephrine and a five- to tenfold elevation of plasma dopamine is likely pathognomonic of dopamine beta-hydroxylase (DBH) deficiency and distinguishes DBH deficiency from other disorders. DBH enzymatic function depends on the availability of the cofactor ascorbic acid, which is generated by transmembrane ascorbate-dependent reductase CYB561, encoded by CYB561. Therefore, biallelic pathogenic variants in CYB561 result in impaired DBH function with very low levels of norepinephrine but normal levels of dopamine . Other catecholamine disorders, such as aromatic L-amino acid decarboxylase deficiency, have clinical presentations distinct from that of DBH deficiency.

Acquired disorders/ disorders of unknown cause

Source: GeneReviews — "Dopamine Beta-Hydroxylase Deficiency"

Management Guidelines

No clinical practice guidelines for dopamine beta-hydroxylase (DBH) deficiency have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with DBH deficiency, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Dopamine Beta-Hydroxylase Deficiency: Recommended Evaluations Following Initial Diagnosis

Clinical Guidance

Untreated individuals with DBH deficiency should avoid hot environments, strenuous exercise, standing motionless, and dehydration. Nephrotoxic drugs should be avoided.

Source: GeneReviews — "Dopamine Beta-Hydroxylase Deficiency"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Dopamine Beta-Hydroxylase Deficiency"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 6.

Dopamine Beta-Hydroxylase Deficiency: Recommended Surveillance

System/Concern | Evaluation | Frequency

Abnormal cardiovascular regulation

| Assess efficacy of droxidopa for orthostatic hypotension symptoms of abnormal cardiovascular regulation w/adjustment of dosage as needed. | At least annually

Persons on droxidopa should be encouraged to report any adverse events to their physician. | At each visit

Referral to autonomic specialist; the type or dose of anesthesia may need to be modified droxidopa doses regulated. | Prior to undergoing surgical procedures or becoming pregnant.

Kidney function

| • BUN plasma creatinine to assess kidney function

• Plasma magnesium potassium

| At least every 2 yrs; more often in those w/ kidney function

BUN = blood urea nitrogen

Source: GeneReviews — "Dopamine Beta-Hydroxylase Deficiency"