Hart Claire E, Race Valerie, Achouri Younes, Wiame Elsa, Sharrard Mark, Olpin Simon E, Watkinson Jennifer, Bonham James R, Jaeken Jaak, Matthijs Gert, Van Schaftingen Emile
Departments of Clinical Chemistry, Sheffield Children's Hospital, Sheffield, UK.
Am J Hum Genet. 2007 May;80(5):931-7. doi: 10.1086/517888. Epub 2007 Mar 30.
We present the first two identified cases of phosphoserine aminotransferase deficiency. This disorder of serine biosynthesis has been identified in two siblings who showed low concentrations of serine and glycine in plasma and cerebrospinal fluid. Clinically, the index patient presented with intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation and died at age 7 mo despite supplementation with serine (500 mg/kg/d) and glycine (200 mg/kg/d) from age 11 wk. The younger sibling received treatment from birth, which led to a normal outcome at age 3 years. Measurement of phosphoserine aminotransferase activity in cultured fibroblasts in the index patient was inconclusive, but mutational analysis revealed compound heterozygosity for two mutations in the PSAT1 gene--one frameshift mutation (c.delG107) and one missense mutation (c.299A-->C [p.Asp100Ala])--in both siblings. Expression studies of the p.Asp100Ala mutant protein revealed a V(max) of only 15% of that of the wild-type protein.
我们报告了首例确诊的磷酸丝氨酸转氨酶缺乏症的两例病例。这种丝氨酸生物合成障碍在两名同胞中被发现，他们的血浆和脑脊液中丝氨酸和甘氨酸浓度较低。临床上，首例患者出现难治性癫痫、后天性小头畸形、张力亢进和精神运动发育迟缓，尽管从11周龄开始补充丝氨酸（500mg/kg/天）和甘氨酸（200mg/kg/天），仍在7个月龄时死亡。年幼的同胞从出生就接受治疗，3岁时结果正常。首例患者培养成纤维细胞中磷酸丝氨酸转氨酶活性的测定结果不明确，但突变分析显示两名同胞的PSAT1基因均存在两个突变的复合杂合性——一个移码突变（c.delG107）和一个错义突变（c.299A→C [p.Asp100Ala]）。对p.Asp100Ala突变蛋白的表达研究显示，其V(max)仅为野生型蛋白的15%。
