Missense variant c.1460 T > C (p.L487P) enhances protein degradation of ER mannosyltransferase ALG9 in two new ALG9-CDG patients presenting with West syndrome and review of the literature.

ALG9-CDG is a CDG-I defect within the group of Congenital Disorders of Glycosylation (CDG). We here describe the clinical symptoms of two new and unrelated ALG9-CDG patients, both carrying the novel homozygous missense variant c.1460 T > C (p.L487P) in the ALG9 gene which led to global developmental delay, psychomotor disability, facial dysmorphisms, brain and heart defects, hearing loss, hypotonia, as well as feeding problems. New clinical symptoms comprised West syndrome with hypsarrhythmia. Quantitative RT-PCR analysis revealed a significantly enhanced ALG9 mRNA transcript level, whereas the protein amount in fibroblasts was significantly reduced. This could be ascribed to a stronger degradation of the mutated ALG9 protein in patient fibroblasts. Lipid-linked oligosaccharide analysis showed an ALG9-CDG characteristic accumulation of Man6GlcNAc2-PP-dolichol and Man8GlcNAc2-PP-dolichol in patient cells. The clinical findings of our patients and of all previously published ALG9-CDG patients are brought together to further expand the knowledge about this rare N-glycosylation disorder. SYNOPSIS: Homozygosity for p.L487P in ALG9 causes protein degradation and leads to West syndrome.

Compliance with recommended immunizations in adolescents.

INTRODUCTION: Little is known about the completeness and timely administration of recommended standard immunizations in Germany. The goal of this study was to determine compliance with official standard immunization recommendations in adolescents attending secondary schools in the city of Erlangen, Germany. METHODS: Adolescents who were attending 5th grade (at approximately 11 years of age), 8th grade (14 years), or 10th and 11th grade (16-17 years) classes at any of the 13 of 14 schools that had agreed to participate were eligible to be enrolled. RESULTS: While coverage for the primary series of diphtheria, tetanus and poliomyelitis immunizations was satisfactory (98%), coverage for measles-mumps-rubella immunizations (dose 1: 89-96%; dose 2: 60-76%) and hepatitis B (doses 1-3: 61%) was suboptimal. Of note, 39% of students had not received any immunization against pertussis. Completion of immunization series generally was significantly delayed. Furthermore, rates for recommended booster doses in adolescence were disappointingly low with 21% for tetanus component vaccines and <10% for the fifth dose of pertussis. CONCLUSIONS: Significant immunization gaps for all recommended standard immunizations in adolescents were detected. This puts individuals at risk for serious vaccine-preventable diseases, contributes to suboptimal herd immunity in the population under study leaving the potential for future epidemics, and impedes national and international targets of disease reduction or elimination.