What is menkes disease?

Menkes Disease, otherwise referred to as Menkes Syndrome or Kinky Hair Disease, affects just one in every 40,000 to 354,507 live births globally, making it an incredibly rare genetic disorder. The disease is associated with a lethal X-linked recessive issue of copper metabolism and is most prevalent in males. It is caused by a mutation of the ATP7A gene, which is pivotal in the protein-encoding processes of the body and is responsible for the absorption and distribution of copper.¹

Diagnosing Menkes Syndrome can be complicated due to the non-specificity of the biochemical markers related to the disease. A failure to clinically diagnose early in one’s life can prove damaging, with identification of the disease essential to elicit proper management and to reduce the risk of morbidity and mortality.¹¹ Despite this, it remains a challenge to most clinicians.²

Key characteristics of menkes disease

Symptoms, diagnosis and treatment

Copper deficiency, stemming from the mutated ATP7A gene, inhibits the body’s reliance on copper-dependent enzymes. This manifests itself in several symptoms:

• Neurodegeneration: The mammalian and human brain should be one of the most abundant copper-containing organs in the body. However, the absence of the ATP7A gene causes a trapping of copper in the blood-brain and blood-cerebrospinal fluid barriers. This causes developmental delays, seizures, progressive neurodegeneration and hypotonia (low muscle tone)
• Connective Tissue Disturbances: Hair (kinky, sparse and brittle) and connective tissue abnormalities manifest as the incomplete delivery of copper to secreted enzymes. Skin laxity and abnormal vascularity are common, too
• Growth and Development: The aforementioned symptoms fail to thrive and develop in the typical way for a healthy subject. This causes delays in developmental milestones

Despite being difficult to diagnose, the procedure for identifying the disease is comparatively straightforward. Observing physical and clinical features (e.g. unique hair abnormalities), testing the genetic ATP7A gene mutation and biochemically measuring copper levels in the blood are the adopted methods.

Outside of nutritional and dietary approaches, treatment will fall into two buckets. The first concern is early treatment, with subcutaneous copper histidine injections relieving some symptoms, especially if started shortly after birth. After that, supportive care facilitates the management of seizures, and physical therapy may improve muscle tone. The feeding difficulties linked with Menkes disease are the primary concern of nutritional support. The following will consider how dietary and nutritional treatment can potentially improve the symptoms of Menkes disease for sufferers.

Dietary and nutritional considerations in menkes disease

An effective nutritional treatment strategy can prove significant in managing one’s quality of life and supporting the overall health of affected individuals. Some evidence supports the use of the aforementioned copper-histidine injections, which effectively reverse skin and hair abnormalities, improve muscle tone, facilitate weight, and achieve neurological development.² This is particularly effective when the disease is identified parenterally (via injection).³ However, this doesn’t answer the question concerning dietary intervention. 

To offer a comprehensive nutritional approach, it is important to consider both the macro- and micronutrient requirements of an individual with the syndrome. Scoping out first and ensuring an adequate caloric intake to support growth as much as possible is crucial. Consulting a dietitian, nutritionist or gastroenterologist is recommended in the literature, but providing sufficient calories, either nasogastrically, via G-tube or normally, is pivotal.⁴ Beyond that, an adequate protein intake will simultaneously support growth and development, which is emphasised to overcome growth delays attributed to Menkes disease.

Well-supported evidence suggests that the intake of essential omega-3 and -6 fatty acids is important for brain health and cognitive function.⁵ Providing a balanced diet with some of these healthy essential fatty acids may benefit Menkes disease symptom-alleviation. Operating from the same train of thought, carbohydrates will likely provide the energy necessary for daily activities whilst supporting metabolism.⁶

It is perhaps at the micronutrient level where the subtle dietary differences can facilitate a meaningful impact and where an individual can benefit from dietary intervention for Menkes disease. Providing sufficient copper, iron, zinc, and vitamins may present transformative benefits. The average intake of dietary copper is 1mg/day in healthy subjects, with absorption.⁷ Occurring across the intestinal lumen and mucosal barrier into the interstitial fluid and blood, ensuring that this average intake is met as a minimum is vitally important. Copper is naturally abundant in many plant and animal foods, including shellfish, nuts and seeds, organ meats, whole grain products and chocolate. It would be advisable to incorporate some of these foods into the diet to meet the recommended dietary allowances in the US (these are consistent with UK recommendations), outlined in Table 1.^8,9

It would also be advisable to aim for a balanced zinc intake equal to copper intake. This is due to its competition with copper in the absorption process. Ensuring a balanced intake of zinc is crucial in an attempt to avoid the exacerbation of copper deficiency. Copper’s interaction with iron is also worth highlighting, as a lack of copper can decrease iron metabolism and cause anaemia. Therefore, it is equally important to include iron-rich food sources in the diet. Some examples include organ meats, red meat, beans, nuts and dried fruit.¹⁰

Similarly, it is important to aim for plentiful sources of essential vitamins. Vitamins B, D, E, C and K will support neurological health and contribute to immunity and overall well-being. Achieving this in the diet is relatively simplistic as a diverse range of whole foods can quickly achieve this for someone suffering from Menkes disease.

Monitoring and evaluation

Regular nutritional assessments that keep on top of the dietary intake of patients with Menkes disease will prove vital in maintaining health. Monitoring growth and development, as well as those biochemical markers, can help assess the effectiveness of dietary intake and identify nutritional areas for adjustment. This ensures that nutritional needs can match growth and the rate of developmental change. This personalised approach is most likely to elicit beneficial outcomes.²

The role of multidisciplinary care

The treatment of Menkes disease, as is the case with most disorders of this nature, is not curable nor solely treatable by means of dietary adjustment. Instead, nutritional tailoring should be a cog in a larger wheel that holistically treats the disease. Evidence indicates that the adoption of a multidisciplinary team tasked with providing their unique expertise to tackle the issues associated with the disease is most fruitful.

A team may include paediatricians, neurologists, genetic counsellors, nutritionists, or dieticians. This collaborative approach is conducive to an all-encompassing provision of healthcare that one of the treatment plans would fail to achieve alone. All aspects of the disease can be managed to ensure the best possible treatment, which becomes fundamental considering there is no specific curative treatment for this progressive, multisystem disease.²

Conclusion

Menke disease is a complex syndrome that can cause real damage to one’s life. Whilst the research attempts to uncover a potential curative solution, the temporary treatment options have shown some real promise. The goal has to be to clinically diagnose the disease as prematurely as possible to increase the chances of the most positive outcomes. From there, the multidisciplinary team of experts, working collaboratively with each individual, has to be the chosen approach.

Within the broader approach, diet, nutrition, and supplementation are large contributors. There is evidence for the success of copper-histidine supplementation via subcutaneous injection, with more anecdotal suggestions supporting the role of diet and specific micro- and macronutrient targets for sufferers of Menkes disease. Monitoring these targets and adjusting them with the rate of growth and development is another key factor to consider. Upon implementing the recommended approaches, it is proposed that a comprehensive guide be available for the nutritional intake of individuals living with Menkes disease. This comprehension does not mitigate the need for personalised considerations but may provide a framework to build.