The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): Case reports of 23 new patients
The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): Case reports of 23 new patients
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DOI：
10.1542/peds.99.4.567
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发表时间：
1997-04-01
期刊：
影响因子：
8
通讯作者：
Lehnert, W
中科院分区：
文献类型：
--
作者：
Gibson, KM;Christensen, E;Lehnert, W
目标.为了进一步确定儿科和代谢专家的疾病的临床谱，并建议一般儿科医生和儿科神经科医生在（特发性）精神发育迟滞患者的鉴别诊断中考虑琥珀酸半醛脱氢酶（SSADH）缺乏症，并强调需要对此类患者进行准确，定量的有机酸分析。本文报告23例SSADH缺乏症（4-羟丁酸尿症）患者（20个家系）的临床特点。诊断时的年龄范围从3个月至25岁的11名男性和12名女性患者，在39%的家庭中发现了血缘关系。观察到以下异常（23例患者的频率）：运动延迟，包括精细运动技能，78%;语言延迟，78%;肌张力减退，74%;智力延迟，74%;癫痫发作，48%;反射减少或缺失，39%;共济失调，30%;行为问题，30%;运动过度，30%;新生儿问题，26%;脑电图异常占26%相关的发现包括精神病，颅磁共振或计算机断层扫描异常，以及22%或更少的患者的眼部问题。氨己烯酸治疗证明在35%的患者中有不同程度的获益。30%的患者早期发育正常。我们的数据表明，存在两组SSADH缺乏症患者，由早期发展过程区分。我们的建议是，对于任何表现出两种或两种以上精神、运动或语言迟缓和不明原因的肌张力减退特征的患者，应要求在适当的专业实验室进行准确、定量的有机酸分析。这种分析是诊断SSADH缺乏症的唯一明确方法;可以通过测定全血中白色细胞的酶活性来证实诊断。我们认为，增加使用有机酸测定将导致增加SSADH缺乏症的诊断和更准确的疾病频率的代表。随着更多患者的发现，我们应该对SSADH缺乏症的代谢和临床特征有更好的了解。
Objectives. To further define the clinical spectrum of the disease for pediatric and metabolic specialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde dehydrogenase (SSADH) deficiency in the differential diagnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative organic acid analysis in such patients.Patients. The clinical features of 23 patients (20 families) with SSADH deficiency (4-hydroxybutyric aciduria) are presented. The age at diagnosis ranged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families.Outcome Measurements. The following abnormalities were observed (frequency in 23 patients): motor delay, including fine-motor skills, 78%; language delay, 78%; hypotonia, 74%; mental delay, 74%; seizures, 48%; decreased or absent reflexes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; neonatal problems, 26%; and electroencephalographic abnormalities, 26%. Associated findings included psychoses, cranial magnetic resonance or computed tomographic abnormalities, and ocular problems in 22% or less of patients. Therapy with vigabatrin proved beneficial to varying degrees in 35% of the patients. Normal early development was noted in 30% of patients.Conclusions. Our data imply that two groups of patients with SSADH deficiency exist, differentiated by the course of early development. Our recommendation would be that accurate, quantitative organic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, motor, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis can be confirmed by determination of enzyme activity in white cells from whole blood. We think that increased use of organic acid determination will lead to increased diagnosis of SSADH deficiency and a more accurate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metabolic and clinical profiles of SSADH deficiency.