Menkes kinky hair disease is a rare X-linked recessive disease nearly exclusively affecting males who present at 2-3 months of age due to abnormal functioning of copper-dependent enzymes due to deficiency of copper. Here, we describe a completely worked-up case of a 4-month-old male infant with very typical history and radiological features confirmed by biochemical and trichoanalysis. The initially seen asymmetric cortical and subcortical T2 hyperintensities in cerebral and cerebellar hemispheres converted into symmetrical diffuse cerebral and predominantly cerebellar atrophy with uniform loss of both white and grey matter on follow-up MRI. Also, subdural hemorrhages of various sizes and different stages and tortuosity of larger proximal intracranial vessels with distal narrowing were identified. Ours is a completely worked-up proven case of Menkes kinky hair disease (MKHD) with history, electroencephalography, biochemical, trichoanalysis, and MRI findings. This is a good teaching case and shows importance of clinical examination and biochemistry as complimentary to MRI. Tortuous intracranial arteries with blocked major vessels are found only in this disease, thus stressing the value of MR Angiography in these patients.
A four-month-old male infant born out of a non-consanguineous marriage at 33 weeks of gestation with perinatal history of cephalhaematoma and hyperbilirubinemia in the neonatal period presented with history of partial seizures and altered sensorium since 4 days which improved with anticonvulsants after 24–48 hours.
Electroencephalogram showed theta-delta range asymmetric background activity with intermittently sharp waves, sharp waves and slow waves seen over left hemisphere, and no further addition by photic stimulation. Metabolic workup done at the time was normal. Initial imaging workup with CT scan of brain revealed mild cerebellar atrophy with area of asymmetrical hypodensities in bilateral posterior parietal subcortical white matter (Figure
Child continued to progress with convulsions and delayed milestones till 8 months of age at which time, on repeat examination, he had reduced tone, inguinal hernia, and poor hair growth (Figure
Characteristic phenotypical appearance of baby—fuzzy sparse thin scalp hairs, fair complexion.
Axial computerized tomography scan shows hypodensities in bilateral posterior parietal subcortical white matter.
Atrophy of the cerebellum with prominence of cerebellar folia. Asymmetric cortical and subcortical hyperintensities on the axial T2WI predominantly in bilateral temporoparietal regions with involvement of the insular cortex.
Metabolic workup revealed increased lactate, decreased serum copper –22 ugm% (N: 75–160), and copper oxidase levels –0.10 OD (N: 0.20–0.55).
MRI showed diffuse bilateral white matter hyperintensities on T2-weighted sequences. Symmetrical cerebral and cerebellar atrophy was seen, the latter being more prominent (Figure
T2(TR: 5000, TE: 102) and fluid-attenuated inversion recovery (TR: 9000, TE: 2500) weighted axial image of brain on Siemens 3 Tesla TIM Trio machine showing bilateral subdural collections of differential intensities suggesting different ages of these hemorrhages.
MR angiography: Axial and coronal maximum intensity projection image of brain on Siemens 3 Tesla TIM Trio machine showing tortuous intracranial vessels (TR: 21.4, TE: 3.8).
Trichoanalysis report suggested weak shape of anagen bulb, weak hair shaft with presence of sheath with anagen-telogen ratio of epilated hair: A-6 and T-4, and diagnosis showed pili torti hair which can be present in both Menkes kinky hair syndrome and twisting hair dystrophy (Figure
Trichoanalysis showing pili torti.
Menkes kinky hair disease (MKHD) or trichopoliodystrophy is a progressive neurodegenerative disorder with an incidence of 1 case per 300000 [
The patients with Menkes disease are preterm or term delivered babies with nonspecific findings like large cephalhematomas, hypothermia, hypoglycemia, and jaundice in perinatal period. There is development of progressive hypotonia, loss of previously obtained developmental milestones, seizures, myoclonic jerks, failure to thrive, poor weight gain, loose skin, pectus excavatum, urinary bladder diverticula, and appearance of the characteristic short, sparse, coarse wiry hair—pili torti—by the time the individual with Menkes kinky hair disease is aged 4-5 months. Death usually occurs by the time the individual with Menkes kinky hair disease is aged 3 years mostly due to respiratory failure [
On
The diagnostic investigation of choice is
MRI at four months of age shows intense bilateral hyperintensities of white matter, very similar to diseases primarily affecting white matter. Hypointense areas on T1-weighted and hyperintense areas on T2-weighted images with volume loss of brain matter suggesting atrophy, necrosis, and gliosis of white matter may be identified before the phenotypic alterations. In such cases, the arteriopathy with vascular insufficiency probably leads to a deficient myelination process, mainly in semioval centers and long tracts [
One unusual case report showed symmetric deep peri-ventricular white matter lesions with diffuse cortical atrophy. Previously reported lesions were usually asymmetric, and they involved lobar white matter rather than deep white matter. These lesions may demonstrate persistent restricted diffusion which may be due to diffuse white matter ischemia as a result of tortuous intracranial vessels [
The most important condition in the differential diagnosis is the shaken baby syndrome. The combination of subdural hygromas and hematomas of different ages and bone fractures is very suggestive of this diagnosis. However, the clinical picture with skin and hair abnormalities, tortuosity of the arteries on MRI, and the presence of other bone abnormalities should help in the differentiation. Differential diagnosis also includes Leigh’s disease (subacute necrotizing encephalopathy), phenylketonuria, and certain diseases with specific hair findings. The low concentrations of copper and ceruloplasmin are however typical only of Menkes disease [
Intravenous copper and copper histidine therapy has been tried [
The authors declare that there is no conflict of interest.