BackgroundAdenylosuccinate lyase deficiency (ADSLD) is an ultrarare neurometabolic recessive disorder caused by loss-of-function mutations in the ADSL gene. The disease is characterized by wide clinical variability. Here we provide an updated clinical profiling of the disorder and discuss genotype-phenotype correlations. ResultsData were collected through "Our Journey with ADSL deficiency Association" by using a dedicated web survey filled-in by parents. Clinical and molecular data were collected from 18 patients (12 males, median age 10.9 years7.3), from 13 unrelated families. The age at onset ranged from birth to the first three years (median age 0.63 years +/- 0.84 SD), and age at diagnosis varied from 2 months to 17 years, (median age 6.4 years +/- 6.1 SD). The first sign was a psychomotor delay in 8/18 patients, epilepsy in 3/18, psychomotor delay and epilepsy in 3/18, and apneas, hypotonia, nystagmus in single cases. One patient (sibling of a previously diagnosed child) had a presymptomatic diagnosis. The diagnosis was made by exome sequencing in 7/18 patients. All patients were definitively diagnosed with ADSL deficiency based on pathogenic variants and/or biochemical assessment. One patient had a fatal neonatal form of ADSL deficiency, seven showed features fitting type I, and nine were characterized by a milder condition (type II), with two showing a very mild phenotype. Eighteen different variants were distributed along the entire ADSL coding sequence and were predicted to have a variable structural impact by impairing proper homotetramerization or catalytic activity of the enzyme. Six variants had not previously been reported. All but two variants were missense.Conclusions The study adds more details on the spectrum of ADSLD patients' phenotypes and molecular data.

Mastrogiorgio, G., Macchiaiolo, M., Buonuomo, P.s., Bellacchio, E., Bordi, M., Vecchio, D., et al. (2021). Clinical and molecular characterization of patients with adenylosuccinate lyase deficiency. ORPHANET JOURNAL OF RARE DISEASES, 16(1), 112 [10.1186/s13023-021-01731-6].

Clinical and molecular characterization of patients with adenylosuccinate lyase deficiency

Bordi, Matteo;Cecconi, Francesco;
2021

Abstract

BackgroundAdenylosuccinate lyase deficiency (ADSLD) is an ultrarare neurometabolic recessive disorder caused by loss-of-function mutations in the ADSL gene. The disease is characterized by wide clinical variability. Here we provide an updated clinical profiling of the disorder and discuss genotype-phenotype correlations. ResultsData were collected through "Our Journey with ADSL deficiency Association" by using a dedicated web survey filled-in by parents. Clinical and molecular data were collected from 18 patients (12 males, median age 10.9 years7.3), from 13 unrelated families. The age at onset ranged from birth to the first three years (median age 0.63 years +/- 0.84 SD), and age at diagnosis varied from 2 months to 17 years, (median age 6.4 years +/- 6.1 SD). The first sign was a psychomotor delay in 8/18 patients, epilepsy in 3/18, psychomotor delay and epilepsy in 3/18, and apneas, hypotonia, nystagmus in single cases. One patient (sibling of a previously diagnosed child) had a presymptomatic diagnosis. The diagnosis was made by exome sequencing in 7/18 patients. All patients were definitively diagnosed with ADSL deficiency based on pathogenic variants and/or biochemical assessment. One patient had a fatal neonatal form of ADSL deficiency, seven showed features fitting type I, and nine were characterized by a milder condition (type II), with two showing a very mild phenotype. Eighteen different variants were distributed along the entire ADSL coding sequence and were predicted to have a variable structural impact by impairing proper homotetramerization or catalytic activity of the enzyme. Six variants had not previously been reported. All but two variants were missense.Conclusions The study adds more details on the spectrum of ADSLD patients' phenotypes and molecular data.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/06
English
Adenylosuccinate lyase deficiency
Epilepsy
Exome sequencing
Intellectual disability
Neurometabolic disease
Purine nucleotide cycle defect
Adolescent
Child
Child, Preschool
Female
Humans
Infant
Infant, Newborn
Male
Phenotype
Adenylosuccinate Lyase
Autistic Disorder
Purine-Pyrimidine Metabolism, Inborn Errors
Mastrogiorgio, G., Macchiaiolo, M., Buonuomo, P.s., Bellacchio, E., Bordi, M., Vecchio, D., et al. (2021). Clinical and molecular characterization of patients with adenylosuccinate lyase deficiency. ORPHANET JOURNAL OF RARE DISEASES, 16(1), 112 [10.1186/s13023-021-01731-6].
Mastrogiorgio, G; Macchiaiolo, M; Buonuomo, Ps; Bellacchio, E; Bordi, M; Vecchio, D; Brown, Kp; Watson, Nk; Contardi, B; Cecconi, F; Tartaglia, M; Bartuli, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/303778
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