Alexander Disease: Report of Two Unrelated Infantile Form Cases, Identified by GFAP Mutation Analysis and Review of Literature; The First Report from Iran
A 15 month-old boy was referred to our hospital for evaluation of seizure disorder and developmental regression. He was the second child of non-consanguineous parents, born at term by elective cesarean section after an uneventful pregnancy. His birth weight and head circumference (HC) were 3.1Kg and 34cm, respectively. Family history was unremarkable. He attained head holding at 7 months of age. Visual fixation and following were not good. First episode of seizure occurred with fever at the age of 5 months. The second episode of seizure occurred without fever at the age of 7 months, and then developmental regression started. Macrocephaly (HC 51 cm), generalized spasticity and searching nystagmus were the main neurological findings. Metabolic tests including High performance liquid chromatography (HPLC) of serum aminoacids, urine organic acid profile, serum ammonia and lactate level and thyroid function tests were within normal limit. Brain MRI showed four of the five diagnostic criteria of Alexander disease described by van der Knapp et al in 2001[, ] ().\nThe diagnosis of AD was confirmed by genetic analysis, which revealed a heterozygous mutation of p.Arg239His in the exon 4 of GFAP gene.\nA 5.5 year-old boy was referred to our hospital for evaluation of developmental regression and seizures. He was the third child of healthy and consanguineous parents, born at term by elective cesarean section after an uneventful pregnancy. His birth weight was 3 Kg, HC at birth was not determined. Family history was unremarkable. At the age of 6 months he had developmental delay and was not able to partial weight bearing. Following the DPT vaccination seizures started and thereafter developmental regression occurred. Significant findings in physical examination were macrocephly (HC 51cm) and spasticity. Laboratory tests similar to the first patient, were all within normal limit. As in case 1, brain MRI showed four of the five diagnostic criteria of AD described by van der Knapp et al in year 2001 (). Genetic study revealed a heterozygous mutation of p.Arg79His in the exon 1 of GFAP gene.\nAccording to the age of onset our two cases were the infantile type. MRI findings were compatible with four of the five criteria of van der Knapp et al (2001)[, ] for the diagnosis of AD. Based on following criteria, AD diagnosis in our patients was wstablished.Periventricular rim (high signal on T1 and low signal on T2-weighted images. Extensive white matter abnormalities predominantly of frontal lobe and cystic degeneration of anterior deep periventricular white matter ( and ). Abnormalities of the basal ganglia and thalami. Brain stem abnormalities especially involving the mid brain area.