Kinetic analyses guide the therapeutic decision in a novel form of moderate aromatic Acid decarboxylase deficiency.

BACKGROUND: Aromatic amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder resulting in a combined dopamine and serotonin deficiency. About 50% of the cases set in the neonatal period. Here, we report an atypical clinical presentation with moderate symptoms. PATIENT: At 10months old, the patient presented paroxysmal eye movements without seizures, and feeding difficulties which were attributed to gastroesophageal reflux. She was investigated at the age of 7years, because of orofacial dyspraxia, hypomimie, axial hypotonia and focal segmental dystonia, bilateral ptosis, without evidence for cognitive impairment. RESULTS: HVA [110nM; (reference value (rv): 202-596)] and HIAA (12nM; rv: 87-366) decreased, OMD (520nM; rv: 5-60) and 5-HTP (56nM; rv: 2-16) increased in CSF. We confirmed the diagnosis of AADC deficiency because the activity in plasma was low: 4pmol/min/ml; rv: 16-137. The kinetic analysis revealed a sixfold increase in the apparent affinity for L-dopa (4.26mM; control=0.71), but the V (max) was unchanged (37.5pmol dopamine/min/ml; control=39.1), suggesting a modification in the substrate binding-site. Molecular analysis revealed two heterozygous mutations in the DDC gene: c1040G > A; pR347Q already described, and a novel mutation c478C > T, pR160W. CONCLUSION: (1) CSF neurotransmitters metabolites suggested a moderate AADC deficiency; (2) The initial velocity saturation curve for L-dopa displayed a cooperative ligand binding behavior, in keeping with the modifications of the three-dimensional structure, induced by the amino acid substitutions (3) The treatment combination of L-dopa with pyridoxine dramatically improved the quality of life, the fatigability, and the paroxysmal eye movements.

[Clinical analysis of paroxysmal motor phenomena in the neonate]. / Diagnostic des mouvements anormaux du nouveau-né

The newborn infant is prone to motor phenomena of various physiological mechanisms and pathological significance whereas they can share close clinical patterns. A detailed clinical analysis, that should be supported by a video EEG recording, is necessary. That may help to distinguish myoclonus, jitteriness or seizures. Some rare phenomenom such as hyperekplexia or myotonia have also to be known. The pregnancy and birth history, the clinical examination and the search for association of various motor phenomena give essential clues for the diagnosis. Misdiagnosing non epileptic phenomona as seizures has to be avoided as it leads to unnecessary anticonvulsivant therapy with potential harmful effects.

Pathological features of neonatal EEG in preterm babies born before 30 weeks of gestationnal age.

Pathological features on very premature EEG concern background abnormalities and abnormal ictal and nonictal patterns. Positive rolandic sharp waves keep an important place regarding diagnosis and prognosis of white-matter lesions. Background abnormalities, that may be classified as acute-stage or chronic-stage abnormalities, give essential complementary information. These abnormal patterns remain precocious markers of cerebral lesions and are complementary to cerebral imaging. Analysis of these abnormalities has always to take into account medication received by the baby during the recording and that could modify the EEG.