Copper‐replacement treatment for symptomatic Menkes disease: ethical considerations

Abstract

We describe a child with classical Menkes disease with a novel ATP7A mutation, intractable seizures, severe hypotonia and developmental delay, hypopigmentation of the skin and hair, and failure to thrive, who was treated with daily subcutaneous copper histidine injections for 2(1/2) years, beginning at 15 months of age. He became seizure-free and pigmentation of his skin and hair darkened, but he continued to have severe developmental delays. His condition remains stable 8 months after stopping treatment. We review the ethical aspects of offering copper treatment for Menkes disease infants diagnosed after neurological symptoms become manifest. These include (1) the prospect for any benefits, (2) the potential risks and discomforts, (3) the parents' wishes with respect to treatment, (4) the family's understanding of the treatment's potential futility, (5) the family's understanding of the investigational nature of this treatment, (6) the potential for treatment to have an adverse impact on unaffected family members, (7) whether the ultimate decision regarding treatment should rest with health care providers or with the patient's parents, and (8) the duration of treatment. The ethical issues encountered in providing possibly futile treatment in this difficult disorder seem relevant to other pediatric medical conditions as well.

ATP7A-related copper transport diseases—emerging concepts and future trends

“…24 In patients with severe loss-of-function ATP7A mutations, for whom outcomes are predicted to be sub optimal even in the context of very early diagnosis and treatment, 24,31,33 copper treatment remains a relevant consideration. 24,85,95 …”

Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes

“…Characteristic is the formation of occipital exostoses resulting from calcification of the trapezius and sternocleidomastoid muscles at their attachments to the occipital bone 13 19. Treatment of MD consists of copper replacement therapy in which the following fundamental issues should be taken into consideration: (1) the block in intestinal absorption of copper must be bypassed, (2) patients must be identified and treatment started as early in life as possible, (3) circulating copper must be delivered to the brain, and (4) copper must be available within cells for cuproenzyme biosynthesis 20 21. The only currently available treatment option consists of administration of copper–histidine, a naturally occurring copper–amino acid complex in serum 22 23.…”

Tandem Duplication of Exons 1–7 Neither Impairs ATP7A Expression Nor Causes a Menkes Disease Phenotype

“…He has achieved normal neurodevelopment throughout infancy up to his current age (24 months), Fig. 2 (continued) without copper replacement treatment (Sheela et al 2005), and his biochemical phenotype has remained normal (Table 1).…”