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Molecular correlates of epilepsy in early diagnosed and treated Menkes disease.

ABSTRACT: Epilepsy is a major feature of Menkes disease, an X-linked recessive infantile neurodegenerative disorder caused by mutations in ATP7A, which produces a copper-transporting ATPase. Three prior surveys indicated clinical seizures and electroencephalographic (EEG) abnormalities in a combined 27 of 29 (93%) symptomatic Menkes disease patients diagnosed at 2 months of age or older. To assess the influence of earlier, presymptomatic diagnosis and treatment on seizure semiology and brain electrical activity, we evaluated 71 EEGs in 24 Menkes disease patients who were diagnosed and treated with copper injections in early infancy (?6 weeks of age), and whose ATP7A mutations we determined. Clinical seizures were observed in only 12.5% (3/24) of these patients, although 46% (11/24) had at least one abnormal EEG tracing, including 50% of patients with large deletions in ATP7A, 50% of those with small deletions, 60% of those with nonsense mutations, and 57% of those with canonical splice junction mutations. In contrast, five patients with mutations shown to retain partial function, either via some correct RNA splicing or residual copper transport capacity, had neither clinical seizures nor EEG abnormalities. Our findings suggest that early diagnosis and treatment improve brain electrical activity and decrease seizure occurrence in classical Menkes disease irrespective of the precise molecular defect. Subjects with ATP7A mutations that retain some function seem particularly well protected by early intervention against the possibility of epilepsy.

SUBMITTER: Kaler SG

PROVIDER: S-EPMC3113468 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Molecular correlates of epilepsy in early diagnosed and treated Menkes disease.

Kaler Stephen G SG Liew Clarissa J CJ Donsante Anthony A Hicks Julia D JD Sato Susumu S Greenfield Jacquelyn C JC

Journal of inherited metabolic disease 20100721 5

Epilepsy is a major feature of Menkes disease, an X-linked recessive infantile neurodegenerative disorder caused by mutations in ATP7A, which produces a copper-transporting ATPase. Three prior surveys indicated clinical seizures and electroencephalographic (EEG) abnormalities in a combined 27 of 29 (93%) symptomatic Menkes disease patients diagnosed at 2 months of age or older. To assess the influence of earlier, presymptomatic diagnosis and treatment on seizure semiology and brain electrical ac ...[more]

PMID: 20652413

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Project description:BackgroundThere is a paucity of research on the prevalence of diagnosed as well as undiagnosed neurological disorders with episodic manifestations such as epilepsy and migraine headaches in people with severe psychiatric disorders (SPD). To the best of our knowledge, this is the first study analyzing and comparing the prevalence of diagnosed and undiagnosed chronic neurological disorders with episodic manifestations including epilepsy and migraine headache in people with SPD.MethodThis quantitative cross-sectional survey was undertaken among 309 patients with SPD selected by a systematic random sampling technique. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to confirm SPD among the participants. The International Classification of Headache Disorders (ICHD-3) and International League Against Epilepsy (ILAE) were used to define migraine headache and epilepsy, respectively]. Risk factors for chronic neurologic disorders were explored by using logistic regression models.ResultIn this study, the prevalence of overall neurological disorders, epilepsy, and migraine headache among people with SPD were found to be 5.2% (95%CI 3.2-8.3), 1.6% (95%CI 0.7-3.9), and 3.9% (95%CI 2.2-6.7), respectively. We found that a considerably higher proportion of people with SPD had undiagnosed overall neurological disorder (87.5%; 14/16), epilepsy (60%; 3/5), as well as migraine headaches (100%; 12/12). On the other hand, in this study, 12.5%, 40%, and 0% of patients with overall neurologic disorder, epilepsy, and migraine headaches respectively were diagnosed by the professionals. Higher disability score (WHODAS score) was associated with increased odds of having neurological disorders compared with the lower WHODAS score [OR = 1.30 (95% CI 1.02-1.66)].ConclusionWhilst the prevalence estimates of neurological disorders with episodic manifestations including epilepsy and migraine headache was high among people with SPD, the vast majority of them remained undiagnosed. The diagnosis rates of those disorders were significantly low, perhaps surprisingly zero for migraine headache. High WHODAS score was associated with increased odds of having neurological disorders. Routine screening and management of epilepsy and migraine headache are imperative among people with SPD.

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Molecular correlates of epilepsy in early diagnosed and treated Menkes disease.

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Molecular correlates of epilepsy in early diagnosed and treated Menkes disease.

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