The hypomyelinating leukodystrophies X-linked Pelizaeus-Merzbacher disease (PMD) and Pelizaeus-Merzbacher-like disease (PMLD) are characterized by nystagmus, progressive spasticity, and ataxia. In a consanguineous family with PMLD, we performed a genomewide linkage scan using the GeneChip Mapping EA 10K Array (Affymetrix) and detected a single gene locus on chromosome 1q41-q42. This region harbors the GJA12 gene, which encodes gap junction protein alpha 12 (or connexin 46.6). Gap junction proteins assemble into intercellular channels through which signaling ions and small molecules are exchanged. GJA12 is highly expressed in oligodendrocytes, and, therefore, it serves as an excellent candidate for hypomyelination in PMLD. In three of six families with PMLD, we detected five different GJA12 mutations, including missense, nonsense, and frameshift mutations. We thereby confirm previous assumptions that PMLD is genetically heterogeneous. Although the murine Gja12 ortholog is not expressed in sciatic nerve, we did detect GJA12 transcripts in human sciatic and sural nerve tissue by reverse-transcriptase polymerase chain reaction. These results are in accordance with the electrophysiological finding of reduced motor and sensory nerve conduction velocities in patients with PMLD, which argues for a demyelinating neuropathy. In this study, we demonstrate that GJA12 plays a key role in central myelination and is involved in peripheral myelination in humans.

The Quantitative Sensory Testing (QST) protocol of the German research network on neuropathic pain (DFNS) encompassing all somatosensory modalities assesses the functioning of different nerve fibers and of central pathways. The aim of our study was: (1) to explore, whether this QST protocol is feasible for children, (2) to detect distribution properties of QST data and the impact of body site, age and gender and (3) to establish reference values for QST in children and adolescents. The QST protocol of the DFNS with modification of instructions and pain rating was used in 176 children aged 6.12-16.12years for six body sites. QST was feasible for children over 5years of age. ANOVAs revealed developmental, gender and body site differences of somatosensory functions similar to adults. The face was more sensitive than the hand and/or foot. Younger children (6-8years) were generally less sensitive to all thermal and mechanical detection stimuli but more sensitive to all pain stimuli than older (9-12years) children, whereas there were little differences between older children and adolescents (13-17years). Girls were more sensitive to thermal detection and pain stimuli, but not to mechanical detection and pain stimuli. Reference values differ from adults, but distribution properties (range, variance, and side differences) were similar and plausible for statistical factors. Our results demonstrate that the full QST protocol is feasible and valid for children over 5years of age with their own reference values.

ABSTRACT. Objectives. To further define the clinical spectrum of the disease for pediatric and metabolic spe cialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde de hydrogenase (SSADH) deficiency in the differential di agnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative or ganic acid analysis in such patients.Patients. The clinical features of 23 patients (20 fam ilies) with SSADH deficiency (4-hydroxybutyric acid uria) are presented. The age at diagnosis ranged from 3

FLIP&FLAP is an effective child- and family-centred programme. It is currently being established in Northern Germany to test its usefulness in routine care.

Almost half of the children with diabetes have subclinical large- and small-fibre neuropathies. Tactile detection was better than vibration for neuropathy assessment. Quantitative sensory testing is a valuable tool for assessment of neuropathy as well as a target of interventional studies in children with diabetes.