RESUMO
OBJECTIVE: To characterize a new lethal fetal and early postnatal variant of adenylosuccinate lyase (ADSL) deficiency. STUDY DESIGN: This was a retrospective analysis of 6 patients with very early presentation of ADSL deficiency. RESULTS: Most of the 6 patients had impaired intrauterine growth, microcephaly, fetal hypokinesia, and a lack of fetal heart rate variability. Postnatally, they shared severe muscular hypotonia necessitating mechanical ventilation, intractable seizures, and early death. All 6 patients had biochemical evidence of severe (type 1) disease and low residual ADSL activities. All were compound heterozygous for mutations that, based on expression studies, have a pronounced effect on ADSL activity and/or stability. CONCLUSIONS: ADSL deficiency may present with prenatal growth restriction, fetal and neonatal hypokinesia, and rapidly fatal neonatal encephalopathy. This clinical presentation is associated with genotypes resulting in very low residual enzyme activity.
Assuntos
Adenilossuccinato Liase/deficiência , Morte Fetal/etiologia , Erros Inatos do Metabolismo da Purina-Pirimidina/enzimologia , Adenilossuccinato Liase/genética , DNA/genética , Evolução Fatal , Feminino , Morte Fetal/enzimologia , Seguimentos , Expressão Gênica , Predisposição Genética para Doença , Humanos , Recém-Nascido , Masculino , Mutação , Gravidez , Erros Inatos do Metabolismo da Purina-Pirimidina/complicações , Erros Inatos do Metabolismo da Purina-Pirimidina/genética , Estudos RetrospectivosRESUMO
Deficiency of the purine salvage pathway enzyme purine nucleoside phosphorylase causes a combined immunodeficiency and neurologic abnormalities and is usually fatal in childhood. We report the first successful transplantation of bone marrow from a sibling with identical class II human leukocyte antigens in this condition, demonstrating correction of both lymphocyte metabolic and functional abnormalities.