Spinal muscular atrophy (SMA) is a clinically and genetically heterogeneous disease characterized by the degeneration of lower motor neurons. The most frequent form is linked to mutations in SMN1. Childhood SMA associated with progressive myoclonic epilepsy (SMA-PME) has been reported as a rare autosomal-recessive condition unlinked to mutations in SMN1. Through linkage analysis, homozygosity mapping, and exome sequencing in three unrelated SMA-PME-affected families, we identified a homozygous missense mutation (c.125C>T [p.Thr42Met]) in exon 2 of ASAH1 in the affected children of two families and the same mutation associated with a deletion of the whole gene in the third family. Expression studies of the c.125C>T mutant cDNA in Farber fibroblasts showed that acid-ceramidase activity was only 32% of that generated by normal cDNA. This reduced activity was able to normalize the ceramide level in Farber cells, raising the question of the pathogenic mechanism underlying the CNS involvement in deficient cells. Morpholino knockdown of the ASAH1 ortholog in zebrafish led to a marked loss of motor-neuron axonal branching, a loss that is associated with increased apoptosis in the spinal cord. Our results reveal a wide phenotypic spectrum associated with ASAH1 mutations. An acid-ceramidase activity below 10% results in Farber disease, an early-onset disease starting with subcutaneous lipogranulomata, joint pain, and hoarseness of the voice, whereas a higher residual activity might be responsible for SMA-PME, a later-onset phenotype restricted to the CNS and starting with lower-motor-neuron disease.

Objective: This retrospective follow‐up study was performed to evaluate the suitability of the recently reported exchange transfusion limits (serum indirect bilirubin level of 428‐496 μmol/1, 25‐29 mg/dl) for Turkey. Material and methods: The study groups totalled 102 children, 8‐13 years of age, who had been born at term with birthweights greater than 3000 g and had been treated for indirect hyperbilirubinemia during their newborn period; the control group consisted of 27 children of the same age‐group without indirect hyperbilirubinemia. Children were grouped according to their maximum serum indirect bilirubin levels and direct Coombs’test results. Physical and neurological examinations, visual and brainstem auditory evoked potentials and the Wechsler Intelligence Scale for Children—Revised for Turkish Children were performed. Results: There was no difference between the groups with regard to mean visual and brainstem auditory evoked potential latencies. Children whose direct Coombs’tests were positive had significantly lower IQ scores and more prominent neurological abnormalities (p < 0.05). IQ scores and prominent neurological abnormalities did not differ among the other groups. Nine children had prominent neurological abnormalities associated with abnormal brainstem auditory evoked potentials. An important risk factor was the duration that the infant's serum indirect bilirubin level remained greater than 342 μmol/1 (20 mg/dl). Conclusion: The current limit of 342 μmol/1 should continue to be used for infants whose direct Coombs’tests are positive in our country. Until better criteria for exchange transfusion other than the indirect bilirubin level are established, the current limits should also still be followed for infants whose direct Coombs’tests are negative in Turkey, where regular neonatal follow‐up examinations are not satisfactory.

We treated 22 patients with subacute sclerosing panencephalitis (SSPE) with intraventricular alpha-interferon (IFN) and inosiplex PO and followed them for 2 to 54 months. Three deaths occurred. Clinical improvement, demonstrated by decreasing scores on the Neurological Disability Index, occurred in 11/22 (50%); five patients became stable, and the progression rate of the disease decreased in three. The remission rate was significantly higher than untreated controls from the same institution. Patients who had a slowly progressive disease responded best to treatment. Serious side effects were rare. We recommend intraventricular IFN, combined with oral inosiplex, in the treatment of SSPE.

On T2-weighted images, WD is suggested by: atrophy; putaminal lesions with a pattern of symmetric, bilateral, concentric-laminar T2 hyperintensity; and the involvement of the pars compacta of the substantia nigra, periaqueductal gray matter, the pontine tegmentum and the thalamus. The hepatic component of WD may cause increased T1 signal intensity in basal ganglia. In the adult age group, the basal ganglia lesions may be different from those in the pediatric group; the putaminal lesions may not be present; the globus pallidus and substantia nigra may show increased hypointensity on T2-weighted images. Cortical and subcortical lesions may also be present with a predilection to the frontal lobe.

Sixteen children with definite multiple sclerosis (MS; aged 6–17 years, mean 11.4 ± 2.7; 8 boys, 8 girls) were reviewed. Cerebellar symptoms and signs were frequent at initial presentation. Among laboratory studies, the cerebrospinal fluid (CSF) IgG index or oligoclonal bands were informative in 75%, evoked potentials in 70%, electroencephalography (EEG) in 83%, magnetic resonance imaging in 80% and computed tomography in 45%. When compared with patients with other neurological disorders and similar presentation (non-MS group, n = 13), MS patients were more likely to recover from the first attack without significant sequelae. CSF protein was usually normal in MS and high in non-MS patients. The CSF IgG index and/or oligoclonal bands were also helpful in differentiating these two groups. The absence of female preponderance, the frequency of EEG abnormalities and the lower yield from CSF analysis are particularly interesting in this childhood series. Different pathogenetic mechanisms may be involved in MS from different ages, genetic backgrounds, or environments.