GALACTORRHEA-A STRONG CLINICAL CLUE TOWARDS THE DIAGNOSIS OF NEUROTRANSMITTER DISEASE

Objectives: We describe 2 siblings from Hong Kong Chinese family who presented with developmental delay and dystonia before 6 months of age and both had hyperprolactinemia with persistent galactorrhea present in the elder brother since birth. Both of them were diagnosed as unexplained mixed type 'cerebral palsy' with mental retardation.

Methods: We had checked their blood and urine for amino and organic acids as well as the serum prolactin level. MRI of the brain including the pituitary region was done. Cerebro-spinal fluid (CSF) for homovanillic acid (HVA), 5- hydroxyindoleacetic acid (5HIAA), 3-O-methyldopa (3-OMD) was checked. DNA study of Tyrosine Hydroxylase (TH) gene of the 2 silbings and their parents were performed.

Results: Metabolic screen on blood and urine was normal. MRI brain was normal. Serum prolactin of the elder brother was raised to 1446 mIU/I (normal <456). His CSF for HVA was very low: 24 nmol/L (reference 218–852) while the 5HIAA and 3-OMD levels were normal. The younger sister also had raised prolactin level: 725 mIU/I (<637) and low CSF HVA: 22 nmol/L (218–852). Both silbings had compound heterozygous mutation for both R169X and R233H of TH gene. They were treated with very low dose of L-dopa with some improvement. Higher dose beyond 2.5mg/Kg/day produced intolerable side effects of hyperkinesia.

Conclusion: To our knowledge, these are the first reported cases of TH deficiency among ethnic Chinese. Our patients' clinical manifestations are very similar to those previously reported in literature. Persistent galactorrhea on expression is a strong clinical clue and elevated serum prolactin level is a useful biochemical marker. TH deficiency is ammendable to treatment with L-dopa. Symptomatic improvement can be achieved with small dosages which should be titrated and increased very slowly to prevent drug-induced hyperkinesias.