Infantile Alexander Disease with Late Onset Infantile Spasms and Hypsarrhythmia.

Alexander disease (AxD) is a rare autosomal dominant leukodystrophy with three clinical subtypes: infantile, juvenile and adult. Forms differ by age of symptoms occurrence and the clinical presentation. Although recent data suggest considering only two subtypes: type I (infantile onset with lesions extending to the cerebral hemispheres); type II (adult onset with primary involvement of subtentorial structures). Dominant mutations in the glial fibrillary acidic protein (GFAP) gene in AxD cause dysfunction of astrocytes (a type III intermediate filament). The authors discuss the clinical picture of a boy with infantile form of AxD confirmed by the presence of de novo heterozygous mutation c.236G>A in the GFAP gene and without striking symptoms such as macrocephaly and with exceptional late-onset epileptic spasms with hypsarrhyth- mia on electroencephalogram (EEG).

Magnetic resonance spectroscopy and molecular studies in ornithine transcarbamylase deficiency novel mutation c.802A>G in exon 8 (p.Met268Val).

Ornithine transcarbamylase (OTC) deficiency, an X-linked, semidominant disorder, is the most common inherited de-fect in ureagenesis, resulting in hyperammonaemia type II. The OTC gene, localised on chromosome X, has been mapp-ed to band Xp21.1, proximate to the Duchenne muscular dystrophy (DMD) gene. More than 350 different mutations, including missense, nonsense, splice-site changes, small de-letions or insertions and gross deletions, have been describ-ed so far. Almost all mutations in consensus splicing sites confer a neonatal phenotype. Most mutations in the OTC gene are 'private' and are distributed throughout the gene with a paucity of mutation in the sequence encoding the leader peptide (exon 1 and beginning of exon 2) and in exon 7. They have familial origin or occur de novo. Even with sequencing of the entire reading frame and exon/intron boundaries, only about 80% of the mutations are detected in patients with proven OTC deficiency. The remainder probably occur within the introns or in regulatory domains. The authors present a 4-year-old boy with the unreported missense mutation c.802A>G. The nucleotide transition leads to amino acid substitution Met to Val at codon 268 of the OTC protein.

Do children with Adams-Oliver syndrome require endocrine follow-up? New information on the phenotype and management.

Adams-Oliver syndrome (AOS) is a rare genetic condition in which the main diagnostic criteria are terminal transverse limb defects and aplasia cutis congenita. Within the spectra of the clinical phenotype of AOS, anthropometric abnormalities have also been reported. We present growth pattern along with hormonal assays in three patients with AOS, one being treated with growth hormone (GH). In Patient 1 (a boy, age 1.9 years), with delayed psychomotor development, epilepsy, deficits of body mass and height, cryptorchidism, low insulin-like growth factor (IGF-1) levels were found and magnetic resonance imaging (MRI) revealed hypoplasia of midline structures of the central nervous system (CNS). In Patient 2 (a girl, age 3.6 years) no significant abnormalities in development, body mass, height or neuroimaging were found. In Patient 3 (a girl, age 8.2 years), with delayed psychomotor development and short stature, low IGF-1 levels and partial GH deficiency were found; MRI revealed small pituitary and polymicrogyria. The girl started GH treatment, improving height velocity and gross coordination. Based on these observations, it seems that intensity of auxologic and hormonal deficits in children with AOS is associated with CNS lesions. Hence, there are indications for neuroimaging and interdisciplinary follow-up of psychomotor development, growth and puberty in this subset of patients with AOS.