Dados do Trabalho

Título

Sialuria and generalized epilepsy: a first case report

Apresentação do caso

A 16-year-old female patient with onset of tonic-clonic seizures and typical absences by the age of two, initially on a weekly basis, had partial seizure control after valproic acid introduction. Her medical records had no significant remarks in the neonatal period and no family history of epilepsy or consanguinity. During clinical follow-up, she displayed a mild neuropsychomotor development delay, besides hepatomegaly and a slight increase in transaminases. By that time, facial dysmorphisms were evident, including: fusion of the eyebrows, a bulging forehead, upward slant of palpebral fissure, low implanted ears and clinodactyly of the 5th fingers. EEG was performed, which showed a mild background activity slowing and 4 Hz generalized spike-and-wave and polyspike-and-wave complexes. Brain MRI and karyotype were unrevealing; exome sequencing, however, showed a heterozygous mutation in exon 5 of the GNE gene. Levels of free urinary sialic acid were high, and a diagnosis of sialuria was made.

Discussão

Sialuria is a rare inborn error of metabolism, with autosomal dominant inheritance, and is characterized by overproduction of sialic acid, causing cytoplasmic accumulation and increased urinary excretion of this molecule. Its pathophysiology rests on the failure of feedback inhibition of the sialic acid synthesis pathway limiting enzyme, encoded by the GEN gene on 9p13.3. Heterozygous missense variants at two allosteric sites (Arginine 294 and Arginine 297) have been implicated in the development of sialuria. This condition was first described in 1968, and since then only ten cases have been reported. Signs and symptoms include neonatal jaundice, hepatomegaly, short stature, and hypotonia. In addition, seizures were described in four patients, mostly relating to febrile seizures; none of them presented with unprovoked absence seizures and interictal EEG abnormalities typical of genetic/idiopathic generalized epilepsies.

Comentários finais

Sialuria is a very rare genetic disorder; the patient described here is the eleventh case, and the first one associated with generalized epileptogenesis and absence seizures.