Weizmann Institute of Science, Rehovot, Israel.
Departments of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Department of Biochemistry, Hamamatsu University School of Medicine, Shizuoka, 431-3192, Japan.
Eur J Med Genet. 2020 Dec;63(12):104061. doi: 10.1016/j.ejmg.2020.104061. Epub 2020 Sep 3.
Adenylosuccinate lyase deficiency is a rare autosomal recessive disorder of purine metabolism. The disorder manifests with developmental delay, postnatal microcephaly, hypotonia, involuntary movements, epileptic seizures, ataxia and autistic features. Paroxysmal non-epileptic motor events are not a typical presentation of the disease. We describe an 8-year-old boy who presented with an infantile onset of prolonged episodes of multifocal sustained myoclonic tremor lasting from minutes to days on a background of global developmental delay and gait ataxia. Ictal EEG during these episodes was normal. Ictal surface EMG of the involved upper limb showed a muscular activation pattern consistent with cortical myoclonus. Brain MRI showed mild cerebral atrophy. Whole exome sequencing revealed a novel homozygous variant in the ADSL gene: c.1027G > A; p. Glu343Lys, inherited from each heterozygous parent. There was a marked elevation of urine succinyladenosine, confirming the diagnosis of adenylosuccinate lyase deficiency. In conclusion, myoclonic tremor status expands the spectrum of movement disorders seen in adenylosuccinate lyase deficiency.
腺嘌呤琥珀酸裂解酶缺乏症是一种罕见的嘌呤代谢常染色体隐性遗传病。该疾病表现为发育迟缓、出生后小头畸形、张力减退、不自主运动、癫痫发作、共济失调和自闭症特征。阵发性非癫痫性运动事件并不是该疾病的典型表现。我们描述了一名 8 岁男孩,他以婴儿期起病,出现长时间多灶性持续肌阵挛性震颤,持续数分钟至数天,伴有全面发育迟缓伴步态共济失调。这些发作期间的发作期 EEG 正常。受累上肢的发作期表面肌电图显示与皮质肌阵挛一致的肌肉激活模式。脑 MRI 显示轻度脑萎缩。全外显子组测序显示 ADSL 基因的一个新的纯合变异:c.1027G>A;p.Glu343Lys,分别从每个杂合子父母遗传。尿琥珀酰腺苷酸显著升高,证实了腺嘌呤琥珀酸裂解酶缺乏症的诊断。总之,肌阵挛震颤状态扩展了腺嘌呤琥珀酸裂解酶缺乏症所见运动障碍的范围。