Menkes\' disease

Clinical History

A 14-week-old male child presented with a history of lethargy and poor feeding. Physical examination revealed pallor, poor tone and sparse, kinked hair. A focal seizure was witnessed following his hospital admission.
A metabolic screen revealed low serum copper and caeruloplasmin. A skeletal survey was requested.

Imaging Findings

The radiographs were performed as a baseline to assess bone density, and to look for fractures. In the peripheral skeleton, there was metaphyseal flaring and spur formation; this was most marked around the knees and wrists. Wormian bones were seen adjacent to the lambdoid suture. A later MR brain angiogram demonstrated mild tortuosity of the intracranial vessels.
The combined clinical, biochemical and radiological findings were in keeping with Menkes’ disease.

Discussion

Menkes’ disease is an inherited X-linked recessive neurodegenerative condition with a prevalence of around 1 in 250,000 live births. Affected patients have deficient or dysfunctional copper transporting ATPase, ATP7A. This leads to decreased activity of enzymes requiring copper as a co-transporter, which leads in turn to reduced bone matrix formation and osteopenia, increased bone fragility and intracranial haemorrhage secondary to diffuse arterial abnormalities. The diagnosis is confirmed by measuring the serum levels of copper and caeruloplasmin, which will be low. Mutations in ATP7A, the copper transport gene can be confirmed by DNA analysis.

Clinically, the condition is characterised by sparse, abnormally kinked hair, neurological degeneration with developmental delay, hypothermia, seizures and intracranial haemorrhage. Osteopenia and increased fragility of bone leads to both metaphyseal and diaphyseal fractures, which can occur after only minor trauma. Copper deficiency can also lead to immune deficiency and increased infections.

Conventional MRI will show delayed myelination and brain atrophy as the condition progresses. MR angiography will confirm any intracranial vascular anomalies. Elevated CSF lactate has been described in Menkes’ disease, and may result in a lactate peak on MR spectroscopy. A skeletal survey of radiographs will add further supportive evidence, if osteopenia, metaphyseal spurs, fractures and Wormian bones are seen. Older children with Menkes’ disease may show a delay in bone age, undertubulation of the long bones and metaphyseal widening. Bladder diverticula may be visualised during an ultrasound examination.

Early treatment with subcutaneous injections of copper histidine has been associated with improved survival and slowing of developmental delay, in children with Menkes’ disease. Anti-epileptic medication may provide symptomatic relief for seizures. Supportive long-term enteral feeding is necessary when the child’s swallow becomes unsafe. The condition is invariably fatal with death occurring in most children before the age of 10 years, usually from respiratory failure or a catastrophic intracranial haemorrhage.

To paediatric radiologists, whilst Menkes’ disease itself is rare, it is an important differential diagnosis to consider, in cases of alleged or suspected non-accidental injury (NAI): the skeletal survey findings of metaphyseal spurs and fractures in Menkes’ disease mimic the classical metaphyseal corner fractures seen in NAI. Furthermore, osteogenesis imperfecta, with osteopenia, Wormian bones and fractures, scurvy, with osteopenia, metaphyseal irregularity and subperiosteal new bone formation, and rickets, with metaphyseal irregularities, osteopenia, fractures and subperiosteal new bone formation are conditions, which must be considered in the radiological differential diagnosis of both NAI and Menkes’.

Differential Diagnosis List

Final Diagnosis

Menkes' disease

URL:	https://eurorad.org/case/9079
DOI:	10.1594/EURORAD/CASE.9079
ISSN:	1563-4086