title: Clinical, biochemical, molecular and therapeutic aspects of 2 new cases of 2-aminoadipic semialdehyde synthase deficiency.
abstract: Our aim was to report two new cases of hyperlysinemia type I describing the clinical, biochemical and molecular features of the disease and the outcome of lysine restriction. Two children presented with febrile seizures followed by developmental delay, clumsiness and epilepsy. At age 2 and 8 years a biochemical and genetic diagnosis of hyperlysinemia type I was confirmed and lysine-restricted diet was started in both cases. Three years after initiation of lysine restriction, case 1 had not suffered further seizures. In case 2, tremor and dysmetria improved, but fine motor clumsiness persisted. Mild cognitive impairment was present in both patients despite dietary treatment. Laboratory studies: Plasma, urine and cerebrospinal fluid amino acid concentrations were measured by ion exchange chromatography. Mutation analysis of the AASS gene was performed by directly sequencing the PCR products. The plasma lysine values were higher than 1200 μmol/L in both cases. Additionally, an increase in dibasic aminoaciduria was observed. Lysine restriction decreased plasma lysine values and nearly normalised dibasic aminoaciduria. Mutational screening of the AASS gene revealed that case 1 was a compound heterozygote for c.2662 + 1_2662 + 5delGTAAGinsTT and c.874A>G and that case 2 was a compound heterozygote for c.976_977delCA and c.1925C>G. In conclusion, we present two children with hyperlysinemia type I and neurological impairment in which implementation of lysine-restricted diet achieved a mild improvement of symptoms but did not reverse cognitive impairment. The partial decrease of lysine concentrations and the normalisation of urine excretion of dibasic amino acids after lysine restriction further reinforce the possibility of this therapeutic intervention, although further investigations seem necessary.
authors.affiliation: Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain. Electronic address: mtondo@hsjdbcn.org.
authors.forename: Mireia
authors.initials: M
authors.lastname: Tondo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Calpena
authors.forename: Gema
authors.initials: G
authors.lastname: Arriola
authors.forename: Paloma
authors.initials: P
authors.lastname: Sanz
authors.forename: Loreto
authors.initials: L
authors.lastname: Martorell
authors.forename: Aida
authors.initials: A
authors.lastname: Ormazabal
authors.forename: Esperanza
authors.initials: E
authors.lastname: Castejon
authors.forename: Manuel
authors.initials: M
authors.lastname: Palacin
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ugarte
authors.forename: Carmen
authors.initials: C
authors.lastname: Espinos
authors.forename: Belen
authors.initials: B
authors.lastname: Perez
authors.forename: Belen
authors.initials: B
authors.lastname: Perez-Dueñas
authors.forename: Celia
authors.initials: C
authors.lastname: Pérez-Cerda
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000097:blood / Q000652:urine; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D023061:Gene Order; D005838:Genotype; D006801:Humans; D020167:Hyperlysinemias / Q000175:diagnosis* / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012443:Saccharopine Dehydrogenases / Q000235:genetics
chemical_list: D000596:Amino Acids; C043044:AASS protein, human; D012443:Saccharopine Dehydrogenases
keywords: 2-aminoadipic semialdehyde synthase deficiency; AASS; CSF; Dibasic amino acids; Familial hyperlysinemia; Lysine restriction; MRI; Magnetic resonance imaging; PCR; cerebrospinal fluid; polymerase chain reaction; α-aminoadipate δ-semialdehyde synthase