Menkes Disease: Clinical Presentation and Imaging Characteristics

A 5-month-old term male presented after 2 months of decreased feeding and weight loss and 1 week of eye deviation and behavioral arrest episodes. He had sparse brittle hair, lax skin, and hypotonia. Electroencephalogram revealed frequent bitemporal subclinical seizures. Magnetic resonance imaging (MRI) revealed restricted diffusion within the globus pallidus bilaterally, bitemporal white matter T2 hyperintensities, enhancement within the left amygdala/anterior hippocampus, bifrontal subdural hematomas, diffuse volume loss, and cervical and intracranial arterial tortuosity ([Figs. 1] [2] [3]). Serum copper was 12 µg/dL (reference: 75–153 µg/dL). Ceruloplasmin was 3 mg/dL (reference: 18–37 mg/dL). Molecular testing identified a pathogenic variant in the ATP7A gene (c.897del [p.Leu299Phefs*7]) confirming the diagnosis of Menkes disease, a rare X-linked neurodegenerative disorder of copper metabolism. Males present by 5 to 6 months with failure to thrive, developmental regression, brittle hair, and seizures. Progressive neurodegeneration occurs with death by 3 years. Early treatment with copper histidine may prolong survival but does not improve neurologic outcomes.[1] [2]

Fig. 1 Axial T2 turbo spin echo demonstrates confluent T2 hyperintense signal within the white matter of the temporal lobes (white arrows), with relative preservation of the overlying cortex. Prominence of the cerebellar fissures indicates progressive volume loss (white arrowheads).

Fig. 2 Axial diffusion-weighted imaging shows restricted diffusion within the globus pallidus bilaterally (white arrows).

Fig. 3 Coronal time-of-flight MR angiogram shows marked tortuosity of the cervical and intracranial vessels, particularly the distal cervical internal carotid arteries (white arrows). MR, magnetic resonance.

Imaging is characterized by cerebral and cerebellar atrophy, white matter abnormalities, particularly in the temporal lobes, subdural hematomas, tortuous vessels, and deep gray nuclei signal abnormalities.[3] Recognition of these clinical and imaging features is important to differentiate this disorder from abusive head trauma and to facilitate early diagnosis.

Publication History

Received: 24 January 2022

Accepted: 03 February 2022

Accepted Manuscript online:
04 February 2022

Article published online:
21 April 2022

• References

• 1 Tümer Z, Møller LB. Menkes disease. Eur J Hum Genet 2010; 18 (05) 511-518
• 2 Vairo FPE, Chwal BC, Perini S, Ferreira MAP, de Freitas Lopes AC, Saute JAM. A systematic review and evidence-based guideline for diagnosis and treatment of Menkes disease. Mol Genet Metab 2019; 126 (01) 6-13
• 3 Ahmed MI, Hussain N. Neuroimaging in Menkes disease. J Pediatr Neurosci 2017; 12 (04) 378-382