GM1 gangliosidosis and Morquio B syndrome, both arising from beta-galactosidase (GLB1) deficiency, are very rare lysosomal storage diseases with an incidence of about 1:100,000– 1:200,000 live births worldwide. Here we report the beta-galactosidase gene (GLB1) mutation analysis of 21 unrelated GM1 gangliosidosis patients, and of 4 Morquio B patients, of whom two are brothers. Clinical features of the patients were collected and compared with those in literature. In silico analyses were performed by standard alignments tools and by an improved version of GLB1 three-dimensional models. The analysed cohort includes remarkable cases. One patient with GM1 gangliosidosis had a triple X syndrome. One patient with juvenile GM1 gangliosidosis was homozygous for a mutation previously identified in Morquio type B. A patient with infantile GM1 gangliosidosis carried a complex GLB1 allele harbouring two genetic variants leading to p.R68W and p.R109W amino acid changes, in trans with the known p.R148C mutation. Molecular analysis showed 27 mutations, 9 of which are new: 5 missense, 3 microdeletions and a nonsense mutation. We also identified four new genetic variants with a predicted polymorphic nature that was further investigated by in silico analyses. Three-dimensional structural analysis of GLB1 homology models including the new missense mutations and the p.R68W and p.R109W amino acid changes, showed that all the amino acids replacements affected the resulting protein structures in different ways, from changes in polarity to folding alterations. Genetic and clinical associations led us to undertake a critical review of the classifications of late-onset GM1 gangliosidosis and Morquio B disease.

CGL patients from Turkey had both previously reported and novel mutations of the AGPAT2, BSCL2, and PTRF genes. Our study highlights the early onset of severe metabolic abnormalities and increased risk of end-organ complications in patients with CGL.

Our data suggest that all antiepileptic drugs studied except levetiracetam had varying degrees of deleterious effects on thyroid function.

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Objective : To evaluate the value of neurologic and cardiologic assessment and also the frequency of iron deficiency anemia in children with Breath Holding Spells (BHS). Methods : The hospital charts of patients diagnosed with BHS between 2011 and 2013 were reviewed retrospectively. Results : A total of 165 children (90 boys, 75 girls) with BHS comprised the study group. A matched group of 200 children with febrile convulsions served as controls. Among the first-degree relatives, 13.3% had BHS, 1.8% had febrile convulsions and 12.1% had epilepsy. The spells were cyanotic in 140 (84.8%) children and pallid or mixed in the remainder. BNS type was simple in 46.7% of patients and complicated in the remainder. Eighteen patients had abnormalities in electroencephalography, however only one patient was diagnosed with epilepsy. Sixty nine (47.9%) patients were found to have iron deficiency anemia. Conclusion : Referral of children with clinically definite BHS to pediatric neurology or pediatric cardiology clinics and performance of echocardiography and EEG investigations for exclusion of heart disease or epilepsy appear unnecessary. However, performance of an electrocardiogram to search for prolonged QT syndrome should be considered although no patient in our series had any cardiologic abnormalities.