RESUMEN
Four children in three unrelated families (one consanguineous) presented with lethargy, hyperlactatemia, and hyperammonemia of unexplained origin during the neonatal period and early childhood. We identified and validated three different CA5A alterations, including a homozygous missense mutation (c.697T>C) in two siblings, a homozygous splice site mutation (c.555G>A) leading to skipping of exon 4, and a homozygous 4 kb deletion of exon 6. The deleterious nature of the homozygous mutation c.697T>C (p.Ser233Pro) was demonstrated by reduced enzymatic activity and increased temperature sensitivity. Carbonic anhydrase VA (CA-VA) was absent in liver in the child with the homozygous exon 6 deletion. The metabolite profiles in the affected individuals fit CA-VA deficiency, showing evidence of impaired provision of bicarbonate to the four enzymes that participate in key pathways in intermediary metabolism: carbamoylphosphate synthetase 1 (urea cycle), pyruvate carboxylase (anaplerosis, gluconeogenesis), propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase (branched chain amino acids catabolism). In the three children who were administered carglumic acid, hyperammonemia resolved. CA-VA deficiency should therefore be added to urea cycle defects, organic acidurias, and pyruvate carboxylase deficiency as a treatable condition in the differential diagnosis of hyperammonemia in the neonate and young child.
Asunto(s)
Anhidrasa Carbónica V/deficiencia , Anhidrasa Carbónica V/genética , Hiperamonemia/genética , Adolescente , Secuencia de Bases , Niño , Preescolar , Exones , Femenino , Eliminación de Gen , Variación Genética , Homocigoto , Humanos , Hiperamonemia/terapia , Lactante , Hígado/enzimología , Masculino , Datos de Secuencia Molecular , Mutación Missense , Linaje , Análisis de Secuencia de ADN , TemperaturaRESUMEN
INTRODUCTION: Spinal arachnoid cysts are an infrequently reported cause of abdominal pain in children. In this report, we describe the unusual case of an extradural arachnoid cyst presenting as recurrent abdominal pain in a pediatric patient without any signs of cord or nerve root compression. CASE REPORT: A 14-year-old girl with recurrent abdominal pain as the only symptom of a spinal extradural arachnoid cyst is reported. The patient was incidentally diagnosed with an intraspinal mass on abdominal computed tomography (CT) during the course of investigating her abdominal pain. Magnetic resonance (MR) imaging confirmed the diagnosis of a T11-L2 extradural arachnoid cyst. After resection of the T11-L2 arachnoid cyst, the patient's abdominal pain resolved. To our knowledge, this is the first report describing abdominal pain as the sole presenting feature of a spinal arachnoid cyst in the pediatric population. CONCLUSION: This case illustrates that abdominal pain may be the first and only presentation of spinal arachnoid cysts in children. Spinal pathology should be considered in the differential diagnosis of unexplained abdominal pain, even when there are no other symptoms of spinal disease.