Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency

Abstract

Based on clinical symptoms, CSF neurotransmitters profile is highly indicative for the diagnosis of aromatic l-amino acid decarboxylase deficiency. Treatment options are limited, in many cases not beneficial, and prognosis is uncertain. Only 15 patients with a relatively mild form clearly improved on a combined therapy with pyridoxine (B6)/pyridoxal phosphate, dopamine agonists, and monoamine oxidase B inhibitors.

A rare cause of severe diarrhoea diagnosed by urine metabolic screening: aromatic L-amino acid decarboxylase deficiency

“…According to the literature, the clinical efficacy of dopamine agonists, monoamine oxidase inhibitors, AADC cofactors (pyridoxine and pyridoxal phosphate [PLP]), and anticholinergics remains variable. 2 Commonly used dopamine agonists aimed at improving motor deficits include bromocriptine and pergolide. Selegiline has been reported to improve oculogyric crises, muscle tone and strength, gastro-intestinal function, hypersalivation and sleep patterns, but according to some reports such effects were transient.…”

“…At the moment, even with early diagnosis, the overall prognosis of patients with AADC deficiency remains guarded, particularly in terms of neurological outcomes and autonomic disturbance. 2 …”

“…This particular mutation NM_000790.3(DDC):c.714+4A>T was known to cause AADC deficiency and was by far the most common mutation causing this condition in the Chinese. 2 The patient was given a combination of bromocriptine 2.5 mg twice a day, selegiline 5 mg daily, and vitamin B6 200 mg twice daily for the next 6 months and appeared to have a good response, as inferred by the reduced frequency of diarrhoeal episodes (2-3 times/day), weight gain to 27.7 kg (at latest follow-up), and diminished recourse to potassium supplementation (0.7 mmol/kg/day). He also became more tolerant of higher milk-drip rates (from 50 to 300 mL/h) and volume of fluid intake (1.5 L/day).…”

Kinetic Analyses Guide the Therapeutic Decision in a Novel Form of Moderate Aromatic Acid Decarboxylase Deficiency

“…The AADC enzyme requires pyridoxal-5 0 -phosphate which is the cofactor covalently linked with the K303 residue in the active site, and subsequently bound to the substrate (Burkhard et al 2001). The recessively inherited deficiency of AADC induces a severe neurometabolic disorder with developmental delay, abnormal movements, oculogyric crises, and vegetative symptoms (Brun et al 2010;. The symptoms typically appear in the first months of life.…”

“…Pyridoxine, as the precursor of the AADC cofactor, monoamine oxidase inhibitors, dopamine agonists, anticholinergics, melatonin, L-dopa, and other treatments has been used. The response to treatment was variable, but overall the outcome remains poor (Brun et al 2010;Manegold et al 2009). …”