Introduction of Aromatic L-amino acid decarboxylase deficiency,AADC
芳香族L-胺基酸類脫羧基酵素缺乏症介绍
病因學：
自出生時所產生的代謝異常疾病，致病原因是負責多巴胺（L-dopa）與5-HTP代謝的 aromatic L-amino acid decarboxylase（AADC）酵素缺乏，造成身體多巴胺（Dopamine）與血清素（Serotonin）缺乏，造成嚴重的發展遲緩、眼動危象（oculogyric crises,OGC)以及自律神經系統功能失調（autonomic dysfunction）。
血清素（Serotonin）：
它是作用於血管的一種神經遞質，也有如激素的作用。缺乏時會造成智力與精神方面的障礙。
兒茶酚胺（catecholamine）：
多巴胺、去甲腎上腺素、腎上腺素統稱為兒茶酚胺（catecholamine）。它因與腎上腺素相關，具有激素與神經傳導物的作用。中樞兒茶酚胺代謝路徑造成缺血傷害或許可歸因於腦部新陳代謝率的增加，也可能是腦組織局部血流阻塞與再灌流的重覆損傷。
臨床上表徵：
曾有學者報告指出患者在出生6個月時即出現運動障礙（movement disorder）的症狀，大多數患者會經歷一早期發病的嚴重漸進式腦病變並合併有肌肉張力低下的過程，包括發展遲緩（developmental delay）、極度地肌肉張力低下（extreme hypotonia）、眼動危象（oculogyric crises）與易怒（irritability）等症狀。此動作障礙症候群的現象學研究已在先前的報告中被定義成包括：間歇性的眼動危象（oculogyric crises）、肢體肌肉張力低下（limbdystonia）、全身性的手足徐動症（generalized athetosis）、自主性的活動降低。自主性功能失調為一顯著的心率與血壓的交感調節損傷。在動作知能上有顯著的損傷如說話與溝通上的障礙，而且預後是以相當多變的形式來呈現，患者有神經學上廣泛性的失能發生。
遺傳模式：
為一神經傳導物合成的體染色體隱性遺傳疾病，父母親雙方各帶有此一缺陷基因不分性別，每一胎皆有1/4機率可遺傳此症。此症的致病基因已知為AADC gene，在第７號染色體ｐ１１的位置上。
診斷：
先天代謝異常的生物基因胺酸（biogenic amine）代謝聚積，取決於在腦脊髓液中的高香草酸（hormovanillic）是否呈現低濃度，5-羥基口引口朵乙酸（5-hydroxyindoleacetic acid）與（3-methoxy-4-hydroxyphenyl-ethyleneglycol）的數值。腦脊髓液中有正常的生物喋呤（biopterin）的代謝，腦脊髓液與尿液中則有多巴胺（dopamine）的前軀物質L-dopa上昇。
以上代謝物的測量可以採用高效液相層析技術
（High Performance Liquid Chromatography, HPLC）與氣相層析質譜儀法
（Gas chromatography-mass spectrometry methodsare）來進行。
可在血漿中發現有大量的芳香族L-胺基酸類脫羧基酵素活性降低現象，來作為診斷上輔助。
治療：
維生素B6（Pyridoxine）乃AADC這個酵素的輔脢，在還有部分殘餘酵素活性的病人身上，使用維生素B6與L-DOPA可能會有反應。
採用維生素B6（Pyridoxine）或是L-DOPA、反苯環丙胺Parnate（tranylcypromine）或是Trihexyphenidyl，多巴胺激動劑溴隱亭（bromocriptine）或者（Pergolide）治療在一些患者身上能得到改善。
給予多巴胺促動劑 （dopamine agonists）與單胺氧化酵素抑制劑（MAO inhibitors）的治療是有益的，但是就長遠的預後而言效果仍不甚清楚。
目前主要的藥物以
（１）多巴胺激動劑如溴隱亭（bromocriptine）或Pergolide（２）單胺氧化酵素抑制劑（MAO inhibitors）如Parnate（tranylcypromine）
為主。
其他藥物還有
（３）抗膽鹼類Trihexyphenidyl（即Artane）或是採用
（４）維生素B6（Pyridoxine）（５）L-DOPA等。
有些疾病的治療反應有性別差異，雖有部分假說嘗試解釋，但尚未有結論。
建議患者除了需與醫師配合，耐心使用藥物之外，還需至早療門診，做評估與復健治療。
預後：
大多數患者表現情緒脆弱與易怒的現象，其他特徵包括肌陣攣（myoclonu）、肌肉張力低下（dystonia）、陣發性冷汗（paroxysmal sweating）、腸胃問題，比如胃食道逆流病（reflux disease）、便秘（constipation）以及腹瀉（diarrhea），功能性的臨床預後並不理想。有50%的患者其症狀在白天會漸漸地嚴重，意即晝現的波動（diurnal fluctuation）或睡著之後症狀會漸漸地改善，治療的反應是多變性的。
What is aromatic l-amino acid decarboxylase deficiency?
Aromatic l-amino acid decarboxylase (AADC) deficiency is an
inherited disorder that affects the way signals are passed between certain
cells in the nervous system.
Signs and symptoms of AADC deficiency generally appear in
the first year of life. Affected infants may have severe developmental delay,
weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and
involuntary writhing movements of the limbs (athetosis). They may be lacking in
energy (lethargic), feed poorly, startle easily, and have sleep disturbances.
People with AADC deficiency may also experience episodes called oculogyric
crises that involve abnormal rotation of the eyeballs; extreme irritability and
agitation; and pain, muscle spasms, and uncontrolled movements, especially of
the head and neck.
AADC deficiency may affect the autonomic nervous system,
which controls involuntary body processes such as the regulation of blood
pressure and body temperature. Resulting signs and symptoms can include droopy
eyelids (ptosis), constriction of the pupils of the eyes (miosis),
inappropriate or impaired sweating, nasal congestion, drooling, reduced ability
to control body temperature, low blood pressure (hypotension), backflow of
acidic stomach contents into the esophagus (gastroesophageal reflux), low blood
sugar (hypoglycemia), fainting (syncope), and cardiac arrest.
Signs and symptoms of AADC deficiency tend to worsen late in
the day or when the individual is tired, and improve after sleep.
How common is aromatic l-amino acid
decarboxylase deficiency?
AADC deficiency is a very rare disorder. Only about 100
people with this condition have been identified worldwide.
What genes are related to aromatic
l-amino acid decarboxylase deficiency?
Mutations in the DDC gene cause AADC deficiency. The DDC
gene provides instructions for making the AADC enzyme, which is important in
the nervous system. This enzyme helps produce dopamine and serotonin from other
molecules. Dopamine and serotonin are neurotransmitters, which are chemical
messengers that transmit signals between nerve cells, both in the brain and
spinal cord (central nervous system) and in other parts of the body (peripheral
nervous system).
Mutations in the DDC gene result in reduced activity
of the AADC enzyme. Without enough of this enzyme, nerve cells produce less
dopamine and serotonin. Dopamine and serotonin are necessary for normal nervous
system function, and changes in the levels of these neurotransmitters
contribute to the developmental delay, intellectual disability, abnormal
movements, and autonomic dysfunction seen in people with AADC deficiency.
How do people inherit aromatic
l-amino acid decarboxylase deficiency?
This condition is inherited in an autosomal recessive
pattern, which means both copies of the gene in each cell have mutations. The
parents of an individual with an autosomal recessive condition each carry one
copy of the mutated gene, but they typically do not show signs and symptoms of
the condition.
What other names do people use for aromatic l-amino acid
decarboxylase deficiency?
·
AADC deficiency
·
DDC deficiency
·
dopa decarboxylase deficiency
