Neuropediatrics 2018; 49(S 01): S1-S12
DOI: 10.1055/s-0038-1651850
Oral Communications
Georg Thieme Verlag KG Stuttgart · New York

Long-Term Follow-Up in Two Families with Adenylosuccinate Lyase Deficiency and Genotype: Phenotype Correlations through a Revision of Literature

S. Masnada
1   Department of Brain and Behavior, University of Pavia, Pavia, Italy
,
G. Lesca
3   Department of Genetics, University Hospitals of Lyon, University Lyon1, Lyon, France
,
M. Valente
4   Genomic and post-Genomic Center, National Neurological Institute “C. Mondino,” IRCCS, Pavia, Italy
,
G. Papalia
2   Department of Child and Adolescence Neurology, IRCCS C. Mondino National Neurological Institute, Pavia, Italy
,
A. Pichiecchio
6   Department of Neuroradiology, IRCCS C.Mondino National Neurological Institute, Pavia, Italy
,
V. De Giorgis
1   Department of Brain and Behavior, University of Pavia, Pavia, Italy
,
D. Tonduti
7   Child Neurology Department, Children Ospital V. Buzzi, Milan, Italy
,
D. Ville
8   Department of Pediatric Neurology, University Hospital of Lyon, Lyon, France
,
I. Bousquet
3   Department of Genetics, University Hospitals of Lyon, University Lyon1, Lyon, France
,
L. Pasca
2   Department of Child and Adolescence Neurology, IRCCS C. Mondino National Neurological Institute, Pavia, Italy
,
C. Varesio
2   Department of Child and Adolescence Neurology, IRCCS C. Mondino National Neurological Institute, Pavia, Italy
,
C. Cereda
4   Genomic and post-Genomic Center, National Neurological Institute “C. Mondino,” IRCCS, Pavia, Italy
,
P. Veggiotti
7   Child Neurology Department, Children Ospital V. Buzzi, Milan, Italy
› Author Affiliations
Further Information

Publication History

Publication Date:
27 April 2018 (online)

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    Study Objectives: Adenylosuccinate lyase (ADSL) deficiency is a rare autosomal recessive disorder of purine metabolism resulting in a wide spectrum of disease, from a mild form with intellectual disability and autistic features to fatal form with neonatal onset.

    Methods: We describe the cases of two brothers and two siblings, who developed an early onset encephalopathy with epilepsy, with different severity of the disease and outcome in the two families. We performed genetic analysis and we reviewed the literature to find genotype–phenotype associations.

    Results: Both the two brothers and two siblings displayed psychomotor regression followed by epilepsy. The two brothers displayed a drug-resistant epilepsy with several electrical and electroclinical status epilepticus together with a progressive pyramidal and extrapyramidal syndrome, autistic features, visual, and severe cognitive impairment. In the other two siblings, a self-limiting epilepsy with a less severe encephalopathy was identified. In all of them magnetic resonance imaging showed progressive cerebral atrophy and white matter abnormalities. In the two brothers neurophysiological evaluations (electroencephalograms, visual evoked potentials, and electroretinograms) showed progressive deterioration of signals, while in the two siblings electroencephalography (EEG) showed only epileptiform discharges.

    Genetic analysis revealed different omozygotic mutations on ADSL gene: c.1277G>A, p.R426H in the first family and c.1288G>A, p.D430Asn in the siblings. Reviewing the literature, we have found genotype–phenotype associations in ours and others mutations.

    Conclusion: We will discuss different clinical, EEG, and neuroradiological presentation of the disease and their evolution during time, through a long-term follow-up up. We will define previously unreported genotype–phenotype correlations and therapeutic options specific for ADSL deficiency.


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    No conflict of interest has been declared by the author(s).