General description

Adenylosuccinate lyase deficiency (ADSLD) is a rare autosomal recessive disorder of purine metabolism with profound neurological implications.

ADSLD is primarily characterized by neurological symptoms, with seizures affecting the majority of patients. These seizures often begin within the first year of life and exhibit a complex profile, including partial seizures, tonic seizures, spasms, and myoclonic episodes that are frequently resistant to treatment. EEG findings show distinct patterns, such as poor background organization, hypsarrhythmia with spasms, and generalized epileptic discharges with a frontal or frontotemporal emphasis. Seizure patterns may evolve over time, starting with brief partial motor manifestations and progressing to more complex forms.

Psychomotor development is invariably affected, ranging from profound impairment in severe cases to milder delays in type II cases. Severe forms often lead to early developmental arrest, lack of eye contact, and, in extreme cases, a coma vigil state. Autistic traits, such as repetitive behaviors and agitation, are frequently observed, particularly in type I. Neurological examinations typically reveal early hypotonia, which may later progress to spasticity, along with cortical visual impairment. Motor dysfunctions, including ataxia, dystonia, and pyramidal and extrapyramidal signs, significantly impact mobility.

Most children with ADSLD are born following uncomplicated pregnancies, with normal birth and family histories, and exhibit normal initial growth parameters. Microcephaly is the most common dysmorphic feature, though other variable physical traits, such as brachycephaly, a flat occiput, or facial dysmorphisms, may be present. The severity of neurological symptoms varies, with severe cases displaying symptoms early in the neonatal period, while milder cases may initially appear normal.

References

1. Jurecka, Agnieszka, et al. "Adenylosuccinate lyase deficiency." Journal of inherited metabolic disease 38 (2015): 231-242.
2. Kayfan, Samar, et al. "MRI findings of hypomyelination in adenylosuccinate lyase deficiency." Radiology Case Reports 14.2 (2019): 255-259.
3. Jurecka, Agnieszka, Elzbieta Jurkiewicz, and Anna Tylki-Szymanska. "Magnetic resonance imaging of the brain in adenylosuccinate lyase deficiency: a report of seven cases and a review of the literature." European journal of pediatrics 171 (2012): 131-138.