P95 – 3007: Late onset treatment on Menkes disease with a novel single nucleotide deletion in the ATP7A gene

Abstract

Objective Menkes disease (MD) is an X-linked recessive disorder of copper metabolism caused by mutations in the ATP7A gene. A genotype-phenotype correlation is crucial since early copper treatment contributes to a better neurodevelopmental outcome and longer survival. We report a case with a novel mutation of a single nucleotide deletion which revealed unexpectedly less severe clinical manifestations, while copper treatment was initiated at 23 months old. Methods The index patient at 12 months old had severe hypotonia, ataxia, connective tissue abnormalities, while his mental abilities were satisfactory and no seizures had occurred. Brain MRA revealed pronounced vessel tortuosity. The serum concentration of copper and ceruloplasmin was slightly reduced. The ATP7A gene screening identified a de novo mutation c.368delG in exon 3 and copper uptake was clearly indicative of MD. Subcutaneous copper histidine treatment was initiated at the age of 23 months assuming that less severe phenotype implies residual ATP7A activity. Western Blot analysis was investigated for ATP7A function. Results After 4½ years of copper treatment the child shows a slow but steady improvement in his development. His muscle tone is improving and he is able to stand on his own, however, truncal ataxia is still present. Although not able to speak, he is very communicative. Until now he has no epilepsy. Pili torti disappeared, but there is no change on his joint and skin laxity and vessel tortuosity. Western Blot analysis shows no presence of ATP7A protein. Conclusion A single nucleotide deletion in exon 3 is expected to abolish ATP7A function and result to a severe clinical phenotype. The moderate severity of patient's clinical manifestations, the unfavorable nature of his mutation along with the lack of detection of ATP7A protein in Western Blot analysis speculates that the late-onset treatment with copper histidine may have a favorable effect.