A Deletion in the Long Arm of Chromosome 18 in a Child with Serum Carnosinase Deficiency1
A Deletion in the Long Arm of Chromosome 18 in a Child with Serum Carnosinase Deficiency1
复制标题
血清肌肽酶缺乏症儿童 18 号染色体长臂缺失1
作者：
S. Willi;Yizong Zhang;J. Hill;M. C. Phelan;R. Michaelis;K. Holden
肌肽和安丝氨酸这两种仅存在于肉类中的二肽在血清中被肌氨酸酶降解。一些关于血清肌肽酶缺乏的报道描述了一种不同的表型，从正常到严重的精神运动迟缓，低张力，以及出生第一年的肌阵挛发作。我们报告一位30个月大的女孩，患有低眼压、发育迟缓和震颤。尽管她象征性地吃肉，但她排出了大量的肌肽和安丝氨酸。严格的无肉饮食改善了这些反常现象，但并没有消除。血清肌氨酸酶活性极低。对这名儿童的染色体分析显示，18号染色体的末端缺失，断裂点在q21.3。父母都没有表现出这种缺失，这表明它是在患者或父母的生殖细胞中重新产生的。分子研究显示，患者父亲的18号染色体被删除。患者父亲的尿肌肽排泄和血清肌氨酸酶活性均正常。母亲的肌氨酸酶活性较低。患者的兄弟表现为中度高肌氨酸尿症和中等酶活性，与肌肽酶缺乏症的携带者状态一致。总而言之，这些发现表明，这种酶的基因座位于18号染色体的远端长臂上，这与这种典型的常染色体隐性遗传的不寻常机制是一致的。我们得出的结论是，这名患者可能是该缺陷的半合子，从她的母亲那里得到了缺失的等位基因，由于染色体缺失，没有来自她父亲的等位基因。这是首次报道与血清肌氨酸酶缺乏相关的染色体异常，应该有助于进一步定位编码血清肌氨酸酶的基因。
The dipeptides carnosine and anserine, found exclusively in meats, are hydrolyzed in serum by the enzyme carnosinase. Several reports of serum carnosinase deficiency describe a variable phenotype, which ranges from normal to severe psychomotor retardation, hypotonia, and myoclonic seizures in the first year of life. We report the case of a 30-mo-old girl with hypotonia, developmental delays, and tremor. Although consuming nominal quantities of meat, she excreted large amounts of carnosine and anserine. A strict meat-free diet ameliorated, but did not eliminate, these abnormalities. Serum carnosinase activity was found to be extremely low. Analysis of this child's chromosomes revealed a terminal deletion of chromosome 18 with breakpoint at q21.3. Neither parent exhibited this deletion, suggesting it was generatedde novo in the patient or in a parental germ cell. Molecular studies showed that the patient's paternal chromosome 18 was deleted. Urinary carnosine excretion and serum carnosinase activity were normal in the patient's father. The mother had low carnosinase activity. The patient's brother exhibited moderate hypercarnosinuria and intermediate enzyme activity, consistent with the carrier state for carnosinase deficiency. Cumulatively, these findings suggest that the locus for this enzyme resides on the distal long arm of chromosome 18, and they are consistent with an unusual mechanism for the inheritance of this, typically autosomal recessive, condition. We conclude that this patient is likely hemizygous for the defect, having received the deficiency allele from her mother and, by virtue of the chromosomal deletion, no allele from her father. This represents the first report of a chromosomal abnormality in association with serum carnosinase deficiency and should aid in further localization of the gene encoding serum carnoosinase.