Transdermal rotigotine in the treatment of aromatic <scp>L</scp>‐amino acid decarboxylase deficiency

Mastrangelo, Mario; Caputi, Caterina; Galosi, Serena; Giannini, Maria Teresa; Leuzzi, Vincenzo

doi:10.1002/mds.25303

Cited by 15 publications

(10 citation statements)

References 7 publications

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“…Transdermal rotigotine was extremely effective in improving gross motor functions as well as in normalizing blood prolactin in AADC defect both in these two sisters and in a previously reported 12-year-old boy (Mastrangelo et al 2013). The transient signs of dopaminergic dysregulation, observed in the present patients, but not in the previously reported pediatric patient, could reflect the abovementioned age-related dopaminergic change leading to a possible postsynaptic hyper-recruitment of dopamine receptors (Lee et al 2013;Mastrangelo et al 2013).…”

Section: Discussioncontrasting

confidence: 62%

“…The transient signs of dopaminergic dysregulation, observed in the present patients, but not in the previously reported pediatric patient, could reflect the abovementioned age-related dopaminergic change leading to a possible postsynaptic hyper-recruitment of dopamine receptors (Lee et al 2013;Mastrangelo et al 2013). It is unclear whether sexual differences in morphology and functions of the monoaminergic system, which have been demonstrated in murine models, could also play a role (Reisert and Pilgrim 1991) 14 .…”

Section: Discussionmentioning

confidence: 44%

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Report of Two Never Treated Adult Sisters with Aromatic l-Amino Acid Decarboxylase Deficiency: A Portrait of the Natural History of the Disease or an Expanding Phenotype?

et al. 2014

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Two sisters were diagnosed in their adulthood with aromatic L-amino acid decarboxylase (AADC) deficiency (OMIM#608643). They experienced early myasthenia-like manifestations, myoclonic jerks, oculogyric crises, tremors, and developmental delay during childhood; clinical stabilization afterwards; and spontaneous improvement during adolescence and young adulthood. Two novel pathogenic mutations on DDC gene [p.Tyr37Thrfs*5 (c.105delC) and p.F237S (c.710 T>C)] were associated with undetectable enzyme activity in plasma and only a mild reduction of biogenic amines in cerebrospinal fluid (CSF). The increase of both 3-O-methyldopa and 5-hydroxytryptophan on CSF was the most relevant biochemical alteration denoting AADC defect in these subjects. Transdermal rotigotine remarkably improved their gross motor functions and the asthenic status they complained. The present cases broaden the phenotypic spectrum of AADC deficiency and suggest that (1) AADC defect is not a progressive neurological disease and behaves rather as a neurodevelopmental disorder that improves during the second decade of life; (2) treatment-naïve adults can still respond well to neurotransmitter therapy; and (3) the possibility of a mild presentation of AADC deficiency should be considered when examining young adults with asthenic and parkinsonian symptoms.

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Section: Discussioncontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 44%

Report of Two Never Treated Adult Sisters with Aromatic l-Amino Acid Decarboxylase Deficiency: A Portrait of the Natural History of the Disease or an Expanding Phenotype?

et al. 2014

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“…49 Following observations have expanded the phenotype of movement disorders in AADC deficiency to brady/akinetic and asthenic patterns that during the first year of life may mimic myasthenia condition. [51][52][53][54][55] Hypotonia can be associated with easily elicitable dystonic reactions after external stimuli. 50 In some patients, dystonic postures can be followed by a startle myoclonus.…”

Section: Tyrosine Hydroxylase Deficiency (Omim#191290)mentioning

confidence: 99%

The Spectrum of Early Movement Disorders in Congenital Defects of Biogenic Amine Metabolism

Mastrangelo

Carducci

et al. 2015

J Pediatr Neurol

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This article analyzes the pattern of movement disorders in children with primary defects of biogenic amine metabolism emerging during the first 3?year of life. A PubMed search was performed using the keywords ?monoamine neurotransmitter disorders,? ?congenital defects of biogenic amine metabolism,? ?early onset movement disorders,? ?autosomal dominant guanosine-triphosphate-cyclohydrolase deficiency,? ?autosomal recessive guanosine-tryphosphate-cyclohydrolase deficiency,? ?6-pyruvoyl-tethrahydropterin synthase deficiency,? ?sepiapterin reductase deficiency,? ?dihydropteridine reductase deficiency,? ?tyrosine hydroxilase deficiency,? ?aromatic l-amino acid decarboxylase deficiency,? ?dopamine transporter deficiency,? and ?vesicular monoamine transporter 2.? A personal series of 27 patients affected by these disorders was presented and discussed. Primary defects of biogenic amine metabolism result in a spectrum of movement disorders associated with derangement of postural reaction and global development delay. Movement disorders virtually represent the presentation symptoms in most of these diseases. The prominent early clinical patterns of movement disorders are akinesia (with rigidity or hypotonia) and hyperkinesia (dystonia, myoclonic jerks, and tremor). While some diseases present with a rather stereotyped clinical pattern (i.e., Aromatic l-amino acid decarboxylase, sepiapterin reductase, and Dopamine transporter deficiencies), others (i.e., Guanosine-triphosphate-cyclohydrolase, 6-pyruvoyl tetrahydropterin synthase, dihydropteridine reductase, and tyrosine hydroxylase deficiencies) may present with more pleomorphic features. As a general rule, earlier the onset of the disease is, more severe and generalized is the derangement of motor functions. Inherited disorders of monoamine neurotransmitter metabolism include the few idiopathic movement disorders with the possibility of etiological treatments. For these reasons, they should always be considered in the diagnostic work-up of children with early onset movement disorders.

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“…l -Dopa is not currently used in the majority of AADC deficiency patients, as l -dopa accumulation leads to depletion of SAM that is potentiated by the AADC deficiency [48]. However, three siblings with an homozygous point mutation (c.387 G>A) in exon 3 showed significant response to l -dopa and pyridoxal-5-phosphate, with improvement in dystonia but persistence of behavioral problems.…”

Section: Disorder Of Dopamine Synthesismentioning

confidence: 99%

“…More recently, rotigotine patches have been used with some success [48]. However, the response to dopamine agonists is highly variable, with some reported improvements in voluntary movements and absence of response in others [48, 53]. …”

Section: Disorder Of Dopamine Synthesismentioning

confidence: 99%

Clinical Features and Pharmacotherapy of Childhood Monoamine Neurotransmitter Disorders

Heales

Kurian

2014

Pediatr Drugs

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Childhood neurotransmitter disorders are increasingly recognised as an expanding group of inherited neurometabolic syndromes. They are caused by disturbance in synthesis, metabolism, and homeostasis of the monoamine neurotransmitters, including the catecholamines (dopamine, norepinephrine, and epinephrine) and serotonin. Disturbances in monoamine neurotransmission will lead to neurological symptoms that often overlap with clinical features of other childhood neurological disorders (such as hypoxic ischaemic encephalopathy, cerebral palsy, other movement disorders, and paroxysmal conditions); consequently, neurotransmitter disorders are frequently misdiagnosed. The diagnosis of neurotransmitter disorders is made through detailed clinical assessment, analysis of cerebrospinal fluid neurotransmitters, and further supportive diagnostic investigations. Early and accurate diagnosis of neurotransmitter disorders is important, as many are amenable to therapeutic intervention. The principles of treatment for monoamine neurotransmitter disorders are mainly directly derived from understanding these metabolic pathways. In disorders characterized by enzyme deficiency, we aim to increase monoamine substrate availability, boost enzyme co-factor levels, reduce monoamine breakdown, and replace depleted levels of monoamines with pharmacological analogs as clinically indicated. Most monoamine neurotransmitter disorders lead to reduced levels of central dopamine and/or serotonin. Complete amelioration of motor symptoms is achievable in some disorders, such as Segawa’s syndrome, and, in other conditions, significant improvement in quality of life can be attained with pharmacotherapy. In this review, we provide an overview of the clinical features and current treatment strategies for childhood monoamine neurotransmitter disorders.

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Transdermal rotigotine in the treatment of aromatic L‐amino acid decarboxylase deficiency

Abstract: [No abstract available

Cited by 15 publications

References 7 publications

Report of Two Never Treated Adult Sisters with Aromatic l-Amino Acid Decarboxylase Deficiency: A Portrait of the Natural History of the Disease or an Expanding Phenotype?

Report of Two Never Treated Adult Sisters with Aromatic l-Amino Acid Decarboxylase Deficiency: A Portrait of the Natural History of the Disease or an Expanding Phenotype?

The Spectrum of Early Movement Disorders in Congenital Defects of Biogenic Amine Metabolism

Clinical Features and Pharmacotherapy of Childhood Monoamine Neurotransmitter Disorders

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