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The aim of this study was to evaluate the quality of life in patients with vascular chronic Q fever at time of diagnosis and during follow-up. Based upon the SF-36 questionnaire, the mean physical and mental health of each patient were assessed at 3-month intervals for up to 18 months. A total of 26 patients were included in the study. At time of diagnosis, the mean physical health and mental health score was 50·6 [95% confidence interval (CI) 46·7–54·4] and 44·6 (95% CI 41·6–47·5), respectively. During treatment, the mean physical health score declined significantly by 1·7 points each 3 months (P < 0·001) to 40·8 (95% CI 34·4–45·1). The mean mental health score significantly and steadily increased towards 51·2 (95% CI 46·9–54·3) during follow-up (P = 0·026). A total of 23% of patients were cured after 18 months of follow-up. In conclusion, quality of life at time of diagnosis for patients with vascular chronic Q fever is lower compared to a similar group of patients, matched for age and gender, with an aortic abdominal aneurysmal disease, and physical health decreases further after starting treatment. Considering the low percentage of cure, the current treatment of vascular chronic Q fever patients may require a separate strategy from that of endocarditis in order to increase survival.
The Netherlands experienced an unprecedented outbreak of Q fever between 2007 and 2010. The Jeroen Bosch Hospital (JBH) in 's-Hertogenbosch is located in the centre of the epidemic area. Based on Q fever screening programmes, seroprevalence of IgG phase II antibodies to Coxiella burnetii in the JBH catchment area was 10·7% [785 tested, 84 seropositive, 95% confidence interval (CI) 8·5–12·9]. Seroprevalence appeared not to be influenced by age, gender or area of residence. Extrapolating these data, an estimated 40 600 persons (95% CI 32 200–48 900) in the JBH catchment area have been infected by C. burnetii and are, therefore, potentially at risk for chronic Q fever. This figure by far exceeds the nationwide number of notified symptomatic acute Q fever patients and illustrates the magnitude of the Dutch Q fever outbreak. Clinicians in epidemic Q fever areas should be alert for chronic Q fever, even if no acute Q fever is reported.
Large outbreaks of Q fever in The Netherlands have provided a unique opportunity for studying longitudinal serum antibody responses in patients. Results are presented of a cohort of 344 patients with acute symptoms of Q fever with three or more serum samples per patient. In all these serum samples IgM and IgG against phase 1 and 2 Coxiella burnetii were measured by an immunofluorescence assay. A mathematical model of the dynamic interaction of serum antibodies and pathogens was used in a mixed model framework to quantitatively analyse responses to C. burnetii infection. Responses show strong heterogeneity, with individual serum antibody responses widely different in magnitude and shape. Features of the response, peak titre and decay rate, are used to characterize the diversity of the observed responses. Binary mixture analysis of IgG peak levels (phases 1 and 2) reveals a class of patients with high IgG peak titres that decay slowly and may represent potential chronic cases. When combining the results of mixture analysis into an odds score, it is concluded that not only high IgG phase 1 may be predictive for chronic Q fever, but also that high IgG phase 2 may aid in detecting such putative chronic cases.
Smith–Lemli–Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient
activity of 7-dehydrocholesterol reductase (DHCR7; EC 184.108.40.206), the final enzyme of the cholesterol
biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursor
7-dehydrocholesterol in plasma and tissues. We here report mutations identified in the DHCR7 gene
of 13 children diagnosed with SLOS by clinical and biochemical criteria. We found a high frequency
of the previously described IVS8–1 G > C splice acceptor site mutation (two homozygotes, eight
compound heterozygotes). In addition, 13 missense mutations and one splice acceptor mutation were
detected in eleven patients with a mild to moderate SLOS-phenotype. The mutations include three
novel missense mutations (W182L, C183Y, F255L) and one novel splice acceptor site mutation
(IVS8–1 G > T).
Two patients, homozygous for the IVS8–1 G > C mutation, presented with a severe clinical
phenotype and died shortly after birth. Seven patients with a mild to moderate SLOS-phenotype
disclosed compound heterozygosity of the IVS8–1 G > C mutation in combination with different
novel and known missense mutations.
We report a branch site mutation in the gene of the enzyme tyrosine hydroxylase (TH): a −24t
> a substitution two bases upstream of the adenosine in the branchpoint sequence (BPS) of intron
11. As normal lariat formation is therefore prevented, alternative splicing takes place: use of the BPS
of intron 12 results in skipping of exon 12, whereas the use of a cryptic branch site in intron 11 leads
to partial retention of this intron in the mRNA. This leads in both cases to an aberrant protein
product. In the one case, skipping of exon 12 results in the absence of 32 amino acids. In the other,
retention of 36 nucleotides of intron 11 in the mRNA results in the incorporation of twelve additional
amino acids. The functional consequences of this mutation for the patient, who is also heterozygous
for another previously identified mutation, become apparent in a severe clinical phenotype.
Mutation detection in the Tyrosine Hydroxylase gene (TH) was performed in patients from two
families. DNA sequencing revealed the presence of four novel missense mutations (exon 9 and 14 in
family A, exon 8 and 9 in family B); the mutations were confirmed with restriction enzyme analysis,
and did not occur in control alleles. Three mutations are in the catalytic domain of the enzyme and
one may disturb tetramerization. At the moment, all patients are in the fourth decade of life. For
more than 30 years they have been able to live a normal life with low-dose L-DOPA medication.
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