A very rare cause of infantile spasms
Keywords:Copper transport disease, developmental disability, early diagnosis, electroencephalography, epilepsy, genetic counselling, hair, Menkes kinky hair disease, neurological manifestations
Psychomotor development regression or delay associated with epilepsy represent a diagnostic challenge. The diagnostic approach should take into account age group, epileptic syndrome, physical and neurological data, and organ and/or system involvement. Herein is reported the case of a toddler for whom hair development, epileptic seizure evolution, and electroencephalographic findings were key for Menkes kinky hair disease diagnosis. The typical electroclinical evolution in this syndrome has rarely been previously reported.
A 22-month-old boy, born at 35 weeks, was admitted to the hospital by the age of two months due to epileptic seizures. Physical examination revealed dysmorphic facial features, pectus excavatum, and inguinal hernias. Antiepileptic drugs were initiated and one month later the patient was readmitted with recurrent epileptic seizures. Transfer to a hospital with Pediatric Neurology support was required, where light-toned and pleated skin, sparse hair, failure to thrive, and axial hypotonia were remarked. Initial investigation with general metabolic, neuroimaging, ophthalmological, and microarray study revealed no changes. Electroencephalograms were markedly abnormal, initially with focal changes and later with hypsarrhythmia. Considering the patient’s phenotype, copper serum level was analysed, with null value. Molecular study confirmed Menkes kinky hair disease and copper histidine therapy was initiated.
Menkes kinky hair disease should be considered in infants with global developmental delay, severe hypotonia, refractory epilepsy, and typical hair and skin changes occurring early in life. However, neonatal diagnosis is hampered by age-unspecific signs and symptoms. Despite being a rare and fatal entity, timely diagnosis allowing early therapy institution and avoiding unnecessary additional tests and prompt genetic counseling are of utmost importance.
Hoffmann GF, Zschocke J, Nyhan WL. Inherited Metabolic Diseases. Berlin: Springer; 2017.
Karimzadeh P. Approach to Neurometabolic Diseases from a Pediatric Neurological Point of View. Iranian Journal of Child Neurology. 2015; 9:1-16.
Bierings M, Clayton P, Houwen R. Disorders of Metal Transport (2012) In Saudubray JM, Berghe G, Walter JH eds. Inborn Metabolic Diseases: Diagnosis and Treatment. Berlin: Springer; 2012. 539-40p.
Kaler SG. ATP7A-Related Copper Transport Disorders. 2003 May 9 [cited 2018 Mar 1]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1413/.
Online Mendelian Inheritance in Man (OMIM). URL: http://omim.org/entry/309400. Consulted on 02-04-2018.
Orphanet.URL:http://www.orpha.net/consor/cgibin/OC_Exp.php?lng=EN&Expert=56. Consulted on 02-04-2018.
Kodama H, Fujisawa C, Bhadhprasit W. Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment. Curr Drug Metab. 2012; 13:237–250.
Tümer Z. An overview and update of ATP7A mutations leading to Menkes disease and occipital horn syndrome. Hum Mutat. 2013; 34:417–429.
Genetics Home Reference. URL: https://ghr.nlm.nih.gov/gene/ATP7A#resources. Consulted on 01-03-2018.
Kaler SG. Inborn errors of copper metabolism. Handb Clin Neurol. 2013; 113:1745-54.
Marques JS, Mateus M, Torres T, Santos H, Real MV, Santos F. Visual diagnosis: 8-day-old hypotonic newborn with sparse hair. Pediatr Rev. 2014; 35:e53-e56.
Bahi-Buisson N, Kaminska A, Nabbout R, Barnerias C, Desguerre I, De Lonlay P, et al. Epilepsy in Menkes disease: analysis of clinical stages. Epilepsia. 2006; 47:380-6.
Campistol J, Plecko B. Treatable newborn and infant seizures due to inborn errors of metabolism. Epileptic Disord. 2015; 17:229-42.
Manara R, D’Agata L, Rocco MC, Cusmai R, Freri E, Pinelli L. et al. Neuroimaging Changes in Menkes Disease, Part 1. Am J Neuroradiol. 2017; 38:1850 –57.
Manara R, Rocco MC, D’Agata L, Cusmai R, Freri E, Giordano L. et al. Neuroimaging Changes in Menkes Disease, Part 2. Am J Neuroradiol. 2017; 38:1858-65.
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