Primary Disorders of Neurotransmitter Metabolism: Experience of a Tertiary Center

Neurotransmitter diseases are a group of inherited disorders attributable to a disturbance of neurotransmitter metabolism. Biogenic amines are neurotransmitters with multiple roles including psychomotor function, hormone secretion, cardiovascular, respiratory and gastrointestinal control, sleep mechanisms, body temperature and pain. Given the multiple functions of monoamines, disorders of their metabolism comprise a wide spectrum of manifestations, with motor dysfunction being the most prominent clinical feature. Methods: Case review of 12 patients from 4 families, with primary disorders of biogenic amine metabolism. Results: Aromatic L-amino acid decarboxylase deficiency (4 patients from 2 families), and GTP-cyclohydrolase (8 patients from 2 families) were the two diseases identified. Age at first symptoms varied between 2 months and 6 years. Developmental delay was present in all cases except 2 patients with GTP cyclohydrolase deficiency. The combination of axial hypotonia and limb dystonia was also frequent. Children with aromatic L-amino acid decarboxylase deficiency exhibited temperature instability, oculogyric crisis and disturbances of sleep. The index case of one family with GTP cyclohydrolase deficiency presented with Parkinsonism (bradykinesia, rigidity and hypomimia). Analysis of neurotransmitters and their metabolites in CSF was crucial for the identification of index cases. Response to therapy was variable but in general unsatisfactory except in a family with GTP cyclohydrolase deficiency. Conclusions: These disorders should be considered in the differential diagnosis of paediatric neurodegenerative diseases, in order to allow an adequate therapeutic trial that can favor prognosis.

Achieving K/DOQI Targets with Cinacalcet in Dialysis Patients with Secondary Hyperparathyroidism. A Portuguese Observational Study

Secondary hyperparathyroidism is a common complication of chronic kidney disease. The elevated serum intact parathyroid hormone, phosphorus, calcium and calcium x phosphorus product have been independently associated with an increased relative risk of mortality. The standard therapy for secondary hyperparathyroidism, including active vitamin D analogues and phosphate binders, is often insufficient to allow patients to achieve the recommended Kidney Disease Outcomes Quality Initiative targets for bone and mineral metabolism. Randomised controlled phase III clinical studies in chronic kidney disease patients with secondary hyperparathyroidism have shown that cinacalcet treatment increases the proportion of patients achieving the recommended Kidney Disease Outcomes Quality Initiative targets for intact parathyroid hormone, phosphorus, calcium and calcium x phosphorus product. Aims: This observational multicentre study aims to evaluate cinacalcet’s ability to achieve and maintain Kidney Disease Outcomes Quality Initiative targets in a population with secondary hyperparathyroidism on chronic haemodialysis in Portugal. Patients and Methods: Patients on chronic dialysis that received cinacalcet during a free sampling programme were enrolled. Retrospective and prospective monthly data were collected from 3 months before until 6 months after the beginning of cinacalcet treatment. Additional assessment included a 12 month evaluation of all parameters. Results: 140 dialysis patients with secondary hyperparathyroidism were enrolled, 60% male, mean age 57.4±14.1 years. The mean intact parathyroid hormone, calcium, phosphorus, and calcium x phosphorus product values at baseline were 751.7±498.8 pg/ml, 9.7±3.8 mg/dl, 5.5±1.5 mg/dl, and 52.7±25.3 mg2/dl2, respectively. After 6 months’ cinacalcet treatment, 26.2%, 53.6%, 59.3%, and 81.0% of the patients achieved the Kidney Disease Outcomes Quality Initiative recommended levels for intact parathyroid hormone, calcium, phosphorus, and calcium x phosphorus product, respectively. The mean dose of cinacalcet at 6 months was 57.1±29.7 mg/day. Conclusions: The use of cinacalcet in clinical practice is an effective option for the treatment of secondary hyperparathyroidism in chronic dialysis patients, allowing more patients to reach and maintain the Kidney Disease Outcomes Quality Initiative targets.