RESUMO
INTRODUCTION: CAD (MIM*114010) encodes a large multifunctional protein with the enzymatic activity of the first three enzymes initiating and controlling the de novo pyrimidine biosynthesis pathway. Biallelic pathogenic variants in CAD cause the autosomal recessive developmental and epileptic encephalopathy 50 (MIM #616457) or CAD deficiency presenting with epilepsy, status epilepticus (SE), neurological deterioration and anemia with anisopoikilocytosis. Mortality is around 9% of patients, mainly related to the no use of its specific treatment with uridine. Majority of reported cases have an early onset during infancy, with some few starting later in childhood. CASE REPORT: Here we report a deceased female patient with CAD deficiency whose epilepsy started at 14 years. She showed a rapid neurologic deterioration including cognitive decline, electroencephalographic background slowing which later evolved to a fatal refractory SE and supra and infratentorial atrophy on neuroimaging. Anemia developed after SE onset. METHODS AND RESULTS: her post-mortem whole exome sequencing identified biallelic missense variants in CAD (NM_004341.5): c.[2944G > A];[5366G > A] p.[(Asp982Asn)];[(Arg1789Gln)]. Our review of twenty-eight reported cases (2015-2023) revealed an epilepsy age onset from neonatal period to 7 years and the SE prevalence of 46 %. DISCUSSION: With our case, we highlight the relevance of suspecting this treatable condition in older patients and in SE with no evident etiology.
Assuntos
Epilepsia , Humanos , Feminino , Epilepsia/genética , Adolescente , Di-Hidro-Orotase/genética , Mutação de Sentido Incorreto , Estado Epiléptico/genética , Disfunção Cognitiva/genética , Idade de Início , Aspartato Carbamoiltransferase , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)RESUMO
Mujer de 50 años, con historia de 3 semanas de cefalea ortostática progresiva y síntomas neurológicos inespecíficos, confirmándose higroma subdural a nivel C5 con fuga de líquido cefalorraquídeo compatible con Síndrome de Hipotensión Intracraneal Espontánea (SHIE). Tratamiento médico inicial sin respuesta. Se realiza parche sanguíneo epidural (PSE) a nivel torácico con 20 ml de sangre directo a través de trocar epidural, observándose respuesta terapéutica completa en seguimiento hasta 8 meses. Creemos que un PSE torácico ofrece las ventajas de uno cervical y lumbar y, por lo tanto, debe considerarse una alternativa terapéutica eficaz en este síndrome especialmente en pacientes anatómicamente complejos.
A 50-year-old woman, with a history of three-week orthostatic headache and nonspecific neurological symptoms, has a subdural hygroma at C5 level with a cerebrospinal fluid leakage compatible with Spontaneous Intracranial Hypotension Syndrome (SIHS). Initial conservative treatment has no response. A thoracic epidural blood patch (EBP) is performed, with a 20ml blood volume spread through an epidural needle, with a complete therapeutic response up-to 8 months. We believe that a higher blood volume patch through a thoracic approach gives the advantages of cervical and lumbar EBP, and, therefore, should be considered as a therapeutic alternative especially in technical anatomically difficult patients.