DBH gene
Also known as: Norepinephrine deficiency; Noradrenaline deficiency; Orthostatic Hypotension 1
– Includes:
– OMIM#223360 https://omim.org/entry/223360
1. The Disease:
A very rare primary monoamine neurotransmitter synthesis disorder with norepinephrine and adrenaline deficiency that leads to young-onset severe orthostatic hypotension and eyelid ptosis.
2. The symptoms:
DBH deficiency is mainly characterized by severe early onset orthostatic hypotension. Lack of early signs or symptoms does not exclude the diagnosis.
In the neonatal period hypothermia and hypoglycemia can occur.
First symptoms of orthostatic hypotension generally occur in early childhood with reduced exercise intolerance. Orthostatic hypotension is profound and can lead to syncope.
Other symptoms and signs of the selective noradrenergic failure of the sympathetic nervous system are eyelid ptosis, nasal congestion, and primary enuresis. Sweating is normal. The central nervous system appears to be largely spared. Reduced kidney function, anemia and hypomagnesemia are common.
3. Actions to take in case of early diagnosis:
Babies with a positive genetic test (biallelic pathogenic variants in the DBH gene) should be referred immediately to a paediatric neurologist for clinical evaluation, as well as parental education and counselling.
Biochemical correlation is recommended with plasma measurements of catecholamines, which shows undetectable levels of noradrenaline and adrenaline and increased levels of dopamine.
DBHD is a lifelong disease requiring lifetime management and regular follow-up with a Paediatric Neurology Center Management is provided by multidisciplinary team.
Excellent and sustained clinical response can be achieved by precursor therapy with L-threo-dihydroxyphenylserine (L-DOPS/ Droxidopa). Oral administration of 100 to 500 mg of L-DOPS, twice or three times a day, reverses the orthostatic intolerance. For children, a starting dose of 2 mg/kg/day in 2-3 doses eventually increasing to 5-10 mg/kg/day in 2-3 doses seems reasonable. Dose should be titrated individually based on clinical response.
Blood pressure should be monitored regularly and (nightly) hypertension should be avoided (last dose of medication should be given more than 4 hours before bedtime).
Regular follow-up of kidney function, electrolytes, and haematological parameters.
Agents to avoid: untreated individuals should avoid hot environments, strenuous exercise, standing motionless, and dehydration.
Genetic counselling should be offered to at-risk family members.
4. For more information:
Biblio : https://www.ncbi.nlm.nih.gov/books/NBK1474/