Neuropediatrics 2008; 39 - V31
DOI: 10.1055/s-0029-1215744

IAHSP caused by maternal uniparental isodisomy in ALS2

D Vater 1, U Müller 2, T Herzfeld 2, P Winter 2, H Hackstein 3, N Wolf 1
  • 1Universitätsklinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin, Neuropädiatrie, Heidelberg, Germany
  • 2Justus-Liebig-Universität, Institut für Humangenetik, Gießen, Germany
  • 3Justus-Liebig-Universität, Institut für Klinische Immunologie und Transfusionsmedizin, Gießen, Germany

Introduction: Infantile-onset ascending spastic paralysis (IAHSP) is a rare autosomal recessive early-onset motor neuron disease. A subset is caused by mutations in ALS2 coding for Alsin.

Case report: We report on an eight year old boy with the clinical signs of a progressive bilateral spastic movement disorder. Pregnancy and perinatal period were uneventful. Motor development showed early delay: No sitting or walking without support, crawling with nine months, stiff walking with support at the age of 14 months. At the age of 20 months spastic paralysis of both legs was obvious. Imaging and neurophysiological tests were normal, CSF analysis could not confirm a disorder of neurotransmission. We saw the child first at the age of 6.9 years. Clinical examination showed facial diplegia, intermittent ptosis and symmetric spastic movement disorder more of his legs than of his arms. Probatory treatment with levodopa had no effect. Sequencing of ALS2 revealed a homozygous mutation of the splice acceptor site in exon 10 (IVS9–2A>T). Analysis of the parental ALS2 gene confirmed heterozygosity for the mutation in the mother, but not in the father. Subsequently, in our patient partial maternal isodisomy of chromosome 2 could be demonstrated.

Conclusion: Infantile-onset ascending spastic paralysis is a clinical diagnosis and should be considered as a differenzial diagnosis in children with a progressive spastic tetraparesis with early pseudobulbar involvement. Sequencing of ALS2 reveals mutations in approximately half of the cases. If a mutation seems to be homozygous, both parents have to be examined to exclude rare complex mechanisms such as uniparental disomy in our patient.

Plenarsitzung Neurometabolische Erkrankungen