Antisense oligonucleotides modulate dopa decarboxylase function in aromatic l
-amino acid decarboxylase deficiency

AbstractAromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive metabolic disorder resulting from disease-causing pathogenic variants of the dopa decarboxylase (DDC) gene. The neurological features of AADC deficiency include early-onset hypotonia, oculogyric crises, ptosis, dystonia, hypokinesia, impaired development, and autonomic dysfunction. We report a patient with genetically confirmed AADC deficiency presenting with developmental epileptic encephalopathy (DEE). We report a boy with severe intractable epileptic spasms and DEE. The patient was evaluated for cognitive and neurologic impairment. Exome sequencing revealed a homozygous mutation (NM_000790.4:c.121C > A; p.Leu41Met) in the DDC gene. This case expands the clinical spectrum of AADC deficiency and strengthens the association between dopa decarboxylase deficiency and epilepsy. Additional studies are warranted to clarify the mechanisms linking dopa decarboxylase dysfunction to DEE.

Download Full-text

Human DOPA Decarboxylase: Catalysis and Involvement in Pharmacological Treatments for Parkinson’s Disease and Aromatic Amino Acid Decarboxylase Deficiency

Pharmaceutical Biocatalysis ◽

10.1201/9781003045397-3 ◽

2020 ◽

pp. 83-100

Author(s):

Mariarita Bertoldi ◽

Giada Rossignoli

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Amino Acid ◽

Aromatic Amino Acid ◽

Dopa Decarboxylase ◽

Acid Decarboxylase ◽

Pharmacological Treatments ◽

Amino Acid Decarboxylase ◽

Aromatic Amino Acid Decarboxylase ◽

Decarboxylase Deficiency

Download Full-text

Aromatic L-Amino Acid Decarboxylase Deficiency: Diagnostic Methodology

Clinical Chemistry ◽

10.1093/clinchem/38.12.2405 ◽

1992 ◽

Vol 38 (12) ◽

pp. 2405-2410 ◽

Cited By ~ 60

Author(s):

K Hyland ◽

P T Clayton

Keyword(s):

Cerebrospinal Fluid ◽

Amino Acid ◽

Inborn Error ◽

Gas Chromatography Mass Spectrometry ◽

Dopa Decarboxylase ◽

Acid Decarboxylase ◽

Amino Acid Decarboxylase ◽

Dopamine Biosynthesis ◽

Hydroxyindoleacetic Acid ◽

Decarboxylase Deficiency

Abstract Aromatic L-amino acid decarboxylase (EC. 4.1.1.28) deficiency is a newly described inborn error of metabolism that affects serotonin and dopamine biosynthesis. The major biochemical markers for this disease are increases of L-dopa, 3-methoxytyrosine, and 5-hydroxytryptophan in urine, plasma, and cerebrospinal fluid together with decreased cerebrospinal fluid concentrations of homovanillic acid and 5-hydroxyindoleacetic acid. In addition, concentrations of vanillactic acid are increased in the urine. Specific HPLC and gas chromatography-mass spectrometry methods are described that permit the identification and measurement of these metabolites in the above body fluids. Simplified assays for human plasma L-dopa decarboxylase and liver L-dopa and 5-hydroxytryptophan decarboxylase, used to demonstrate the enzyme deficiency, are also reported.

Download Full-text