In an infant in which epilepsy was the first manifestation of adenylosuccinase deficiency (ADSLD; 103050), Maaswinkel-Mooij et al. (1997) reported homozygosity for an arg401-to-his (R401H) substitution in the ADSL gene.
Marie et al. (1999) found 5 apparently unrelated patients with adenylosuccinate lyase deficiency who had an arg426-to-his (R426H) mutation, which had previously been identified as R401H by Maaswinkel-Mooij et al. (1997). The discrepancy in the numbering system was due to the finding by Marie et al. (1999) that the cDNA of human ADSL encodes a protein of 484 rather than 459 amino acids. The authors noted that 426H mutation was the most frequent one identified to that time, accounting for 12 of the 34 alleles investigated.
Kmoch et al. (2000) described a patient with ADSLD who was homozygous for the R426H mutation.
Edery et al. (2003) observed an unusually variable combination of clinical features and striking intrafamilial variability in the phenotype. Among 3 sibs from a family originally from Portugal, the proband had marked psychomotor regression and progressive cerebellar vermis atrophy; the other 2 affected sibs presented mainly autistic features. The sibs were homozygous for the R426H mutation. The authors suggested that, in any patient with mental retardation of unexplained origin, adenylosuccinate lyase deficiency should be considered and assessed using a simple urinary screening method for the presence of succinylpurines.
Jurecka et al. (2008) identified homozygosity for the R426H mutation in 2 unrelated Polish patients with ADSL deficiency. One had a severe form of the disorder with severe psychomotor retardation, inability to walk, and refractory seizures, and was bedridden by age 9.5. The other had a relatively less severe phenotype and could sit and walk a few steps at age 4.5 years. Two additional unrelated Polish patients were compound heterozygous for the R426H allele and another pathogenic mutation in the ADSL gene.
