芳香族L-氨基酸脱羧酶(AADC)缺乏症是一种罕见的常染色体隐性遗传神经代谢紊乱,导致严重的5-羟色胺联合,多巴胺,去甲肾上腺素,和肾上腺素缺乏.我们报告了一名女性患者,该患者具有10岁起至双侧癫痫发作的边缘功能和零星明确的局灶性发作。神经心理学评估强调了执行功能的轻度损害,影响注意力跨度和视觉空间能力。在诊断为具有推测的遗传病因的癫痫后,我们应用了一种诊断方法,包括下一代测序(NGS)基因组,揭示了AADC缺乏症的DOPA脱羧酶(DDC)基因中的两个反式变体。这种复合杂合基因型与高香草酸的轻度减少有关,低水平的去甲肾上腺素分解代谢物,脑脊液中5-羟基吲哚乙酸显著减少。值得注意的是,3-O-甲基多巴(3-OMD)和5-羟色氨酸反而增加。在基因指导的重新评估过程中,一些轻度的自主神经功能障碍的迹象(鼻塞,不正常的出汗,低血压和昏厥,过度困倦,小手和小脚,催乳素水平升高,疲倦,和疲劳),更典型的AADC缺陷,以新的洞察力进行了评估。在两个AADC变体中,R347Q已经被描述为具有严重催化损伤的功能丧失,而新的L391P变体已被预测具有不太严重的影响。生物信息学分析表明,氨基酸取代可能会影响对PLP辅酶的亲和力。因此,基因型对应于轻度和迟发性症状的表型,其中癫痫发作是临床症状,导致医疗护理。该病例报告扩展了AADC缺乏表型的范围,以涵盖较少致残的临床状况,包括临界认知功能。药物反应性癫痫,和轻度自主神经功能障碍.
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive neurometabolic disorder leading to severe combined serotonin, dopamine, norepinephrine, and epinephrine deficiency. We report on a female patient with borderline functioning and sporadic clear-cut focal to bilateral seizures from age 10 years. A neuropsychological assessment highlighted a mild impairment in executive functions, affecting attention span and visual-spatial abilities. Following the diagnosis of epilepsy with a presumed genetic etiology, we applied a diagnostic approach inclusive of a next-generation sequencing (NGS) gene panel, which uncovered two variants in trans in the DOPA decarboxylase (DDC) gene underlying an AADC deficiency. This compound heterozygous genotype was associated with a mild reduction of homovanillic acid, a low level of the norepinephrine catabolite, and a significant reduction of 5-hydroxyindoleacetic acid in cerebrospinal fluid. Remarkably, 3-O-methyldopa (3-OMD) and 5-hydroxytryptophan were instead increased. During the genetically guided re-evaluation process, some mild signs of dysautonomic dysfunction (nasal congestion, abnormal sweating, hypotension and fainting, excessive sleepiness, small hands and feet, and increased levels of prolactin, tiredness, and fatigue), more typical of AADC deficiency, were evaluated with new insight. Of the two AADC variants, the R347Q has already been characterized as a loss-of-function with severe catalytic impairments, while the novel L391P variant has been predicted to have a less severe impact. Bioinformatic analyses suggest that the amino acid substitution may affect affinity for the PLP coenzyme. Thus, the genotype corresponds to a phenotype with mild and late-onset symptoms, of which seizures were the clinical sign, leading to medical attention. This case report expands the spectrum of AADC deficiency phenotypes to encompass a less-disabling clinical condition including borderline cognitive functioning, drug-responsive epilepsy, and mild autonomic dysfunction.