Aromatic <scp>l</scp>‐amino acid decarboxylase deficiency: clinical features, drug therapy and follow‐up

Manegold, Christian; Hoffmann, Georg F.; Degen, Ingrid; Ikonomidou, H; Knust, A.; Laass, MW; Pritsch, Michael; Wilichowski, Ekkehard; Hörster, Friederike

doi:10.1007/s10545-009-1076-1

Cited by 100 publications

(83 citation statements)

References 21 publications

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“…This clinical pattern broadens the phenotypic spectrum of AADC deficiency (Pons et al 2004;Manegold et al 2009;Lee et al 2009;Brun et al 2010). In a larger series of AADC-deficient patients published so far, the overall mortality associated with the disease was about 10% and the majority of the remaining subjects showed a poor response to the treatment, experiencing a several neurological impairment (Brun et al 2010).…”

Section: Discussionmentioning

confidence: 87%

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: Discussionmentioning

confidence: 87%

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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“…5-HTP is subsequently converted to 5-HT by amino acid decarboxylase, the enzyme also converting L-DOPA to dopamine [98]. Tph exists in two isoforms (1 and 2) that show mostly non-overlapping distribution patterns [99].…”

Section: Tryptophan Hydroxylasementioning

confidence: 99%

The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2^Arg439^Hisknockin mouse

Jacobsen

Medvedev

Caron

2012

Phil. Trans. R. Soc. B

161

105

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A decreased level of brain 5-hydroxytryptamine (5-HT) has been theorized to be a core pathogenic factor in depression for half a century. The theory arose from clinical observations that drugs enhancing extracellular levels of 5-HT (5-HT Ext ) have antidepressant effects in many patients. However, whether such drugs indeed correct a primary deficit remains unresolved. Still, a number of anomalies in putative biomarkers of central 5-HT function have been repeatedly reported in depression patients over the past 40 years, collectively indicating that 5-HT deficiency could be present in depression, particularly in severely ill and/or suicidal patients. This body of literature on putative 5-HT biomarker anomalies and depression has recently been corroborated by data demonstrating that such anomalies indeed occur consequent to severely reduced 5-HT Ext levels in a mouse model of naturalistic 5-HT deficiency, the tryptophan hydroxylase 2 His 439 knockin (Tph2KI) mouse. In this review, we will critically assess the evidence for 5-HT deficiency in depression and the possible role of polymorphisms in the Tph2 gene as a causal factor in 5-HT deficiency, the latter investigated from a clinical as well as preclinical angle.

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“…The fact that patients with growth-hormone deficiency have a higher risk to develop life-threatening hypoglycemic episodes, as seen in our patient, highlights the importance of an early diagnosis of SR deficiency and immediate start of treatment with dopaminergic substances. As hypoglycemic episodes are known and potentially lethal complications in several inherited neurotransmitter disorders including aromatic Lamino acid decarboxylase (AADC) deficiency (Arnoux et al 2013;Manegold et al 2009), analyses of biogenic amines and pterins in CSF should be taken into consideration in children presenting with fasting hypoglycemia and neurologic symptoms.…”

Section: Discussionmentioning

confidence: 99%

Dopamine-Responsive Growth-Hormone Deficiency and Central Hypothyroidism in Sepiapterin Reductase Deficiency

et al. 2015

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Aromatic l‐amino acid decarboxylase deficiency: clinical features, drug therapy and follow‐up

Abstract: AADC deficiency is a severe neurometabolic disorder, characterized by muscular hypotonia, dystonia, oculogyric crises and additional extraneurological symptoms. Medical treatment is challenging, but a systematic trial of the different drugs is worthwhile.

Cited by 100 publications

References 21 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 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2^Arg439^Hisknockin mouse

Dopamine-Responsive Growth-Hormone Deficiency and Central Hypothyroidism in Sepiapterin Reductase Deficiency

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Aromatic l‐amino acid decarboxylase deficiency: clinical features, drug therapy and follow‐up

Abstract: AADC deficiency is a severe neurometabolic disorder, characterized by muscular hypotonia, dystonia, oculogyric crises and additional extraneurological symptoms. Medical treatment is challenging, but a systematic trial of the different drugs is worthwhile.

Cited by 100 publications

References 21 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 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439Hisknockin mouse

Dopamine-Responsive Growth-Hormone Deficiency and Central Hypothyroidism in Sepiapterin Reductase Deficiency

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The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2^Arg439^Hisknockin mouse