We have investigated seven patients with the type B form of pyruvate carboxylase (PC) deficiency.... more We have investigated seven patients with the type B form of pyruvate carboxylase (PC) deficiency. Mutation analysis revealed eight mutations, all novel. In a patient with exon skipping on cDNA analysis, we identified a homozygous mutation located in a potential branch point sequence, the first possible branch point mutation in PC. Two patients were homozygous for missense mutations (with normal protein amounts on western blot analysis), and two patients were homozygous for nonsense mutations. In addition, a duplication of one base pair was found in a patient who also harboured a splice site mutation. Another splice site mutation led to the activation of a cryptic splice site, shown by cDNA analysis.All patients reported until now with at least one missense mutation have had the milder type A form of PC deficiency. We thus report for the first time two patients with homozygous missense mutations with the severe type B deficiency, clinically indistinguishable from other patients with type B form of PC deficiency.The mutations found here are novel; it is noteworthy that four Turkish patients did not have any mutations in common, despite the rarity of PC deficiency. There is thus no evidence for recurrent mutations in the Turkish or other populations.
Metaphyseal chondrodysplasia (MCD) is a heterogeneous group of diseases characterised by defectiv... more Metaphyseal chondrodysplasia (MCD) is a heterogeneous group of diseases characterised by defective enchondral ossification, leading to metaphyseal changes. The different types of MCD can be distinguished by clinical findings, radiology and genetic tests. Based on a case story with MCD, pancreatic insufficiency and granulocytopenia (Shwachman's syndrome), we review the most common types of MCD with regard to clinical manifestations, radiological findings, and genetic background.
The medical records were reviewed for 109 children (0-15 years) who were investigated by abdomina... more The medical records were reviewed for 109 children (0-15 years) who were investigated by abdominal ultrasonography as part of the evaluation of recurrent abdominal pain. We characterised this group of children in an attempt to localise the characteristics that would predict abnormal findings by abdominal ultrasonography. We conclude that neither location, frequency or duration of pain, nor sex nor age have any predictive value. All abnormal findings seen by abdominal ultrasonography could have been revealed by a carefully taken history, thorough clinical examination and commonly performed laboratory tests, such as urine analysis. We recommend that abdominal ultrasonography should only be used in the evaluation of recurrent abdominal pain in children if there are other characteristics, such as a history of cystitis.
We randomised 59 children hospitalized for croup to treatment with either inhaled budesonide or i... more We randomised 59 children hospitalized for croup to treatment with either inhaled budesonide or injected dexamethasone. Group A were treated with two inhalations of 1000 micrograms budesonide and group B received dexamethasone 0.6 mg/kg intramuscularly. We used a modified Westley-score, based on chest-wall retractions, barking cough, respiratory frequency and stridor. The children was aged three months to six years (mean 20 months). Three hours after the first treatment there was significant improvement in score amongst all children (p < 0.001), but no difference between the two groups (p < 0.20). Six and 12 hours after the first treatment there were significantly better clinical scores in group B (p = 0.001, p = 0.0004). Based on this study we recommend dexamethasone 0.6 mg/kg intramuscularly for children to be treated for croup.
Omphalitis is a serious condition with important morbidity and mortality, especially in developin... more Omphalitis is a serious condition with important morbidity and mortality, especially in developing countries. The most commonly involved micro-organisms are Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. We describe a Danish patient with cellulitis, severe septicaemia, and portal vein thrombosis as fatal complications of omphalitis. In spite of early recognition and prompt treatment in this case, it was not possible to save the child.
Associations between the genetic variation within or downstream of the surfactant protein-D-encod... more Associations between the genetic variation within or downstream of the surfactant protein-D-encoding gene (SFTPD), which encodes the collectin surfactant protein-D (SP-D) and may lead to respiratory distress syndrome or bronchopulmonary dysplasia, recently were reported. Our aim was to investigate whether SFTPD variations affect serum SP-D levels in infants and pulmonary outcome in premature infants. Serum SP-D levels were measured in 211 mature and 202 premature infants, and 7 SFTPD single-nucleotide polymorphisms (SNPs) were genotyped. SNP analysis and haplotype analysis were used to associate genetic variation to SP-D, respiratory distress (RD), oxygen requirement, and respiratory support. The 5'-upstream SFTPD SNP rs1923534 and the 3 structural SNPs rs721917, rs2243639, and rs3088308 were associated with the SP-D level. The same SNPs were associated with RD, a requirement for supplemental oxygen, and a requirement for respiratory support. Haplotype analyses identified 3 hapl...
To describe physical outcome and school performance in a cohort of very-low-birthweight infants t... more To describe physical outcome and school performance in a cohort of very-low-birthweight infants treated with early nasal continuous positive airway pressure (NCPAP)/minimal handling regimen with permissive hypercapnia, in comparison to siblings of normal birthweight. Neonatal and follow-up data from 213 very-low-birthweight infants from 1983-1988 were registered and a questionnaire concerning school achievements was sent to the families of survivors and siblings attending school. Mortality was 22%. Of the survivors, 4% had moderate-severe and 9% mild sequelae. Eighty-seven per cent of VLBW children and 95% of their siblings attended regular school. Average or above-average achievement was accomplished by 33 (65%) of the VLBW children and 34 (74%) of the siblings in mathematics, and 35 (69%) and 32 (68%), respectively, in reading/spelling. None of these differences reached statistical significance. However, the performance ratings correlated significantly with socio-economic conditions. In this study of infants treated with a regimen of early NCPAP/minimal handling, we found a relatively low incidence of handicaps and impairments. Nearly 90% attended ordinary schools, with near-average performances in mathematics and reading/spelling, which were not statistically different to their siblings. The overall results indicate that these infants fare at least as well as survivors after conventional treatment.
To develop a rapid method for diagnosing lung maturity at birth with the purpose of administering... more To develop a rapid method for diagnosing lung maturity at birth with the purpose of administering surfactant early to infants with immature lungs and to spare infants with mature lungs from this treatment. Lamellar body counts (LBC) on gastric aspirates from 191 newborns were counted in the platelet window in automatic blood cell counters. A preliminary study was performed on 108 aspirates from 2000 in infants with <32 weeks' gestation. Furthermore, 83 aspirates from 2004 to 2005 in infants with <30 weeks' gestation were analysed. Lamellar bodies in gastric aspirate were identified by electron microscopy. Seventy of the aspirates from 2004 to 2005 were analysed with a Sysmex XE-2100 (Sysmex, Holbaek, Naestved, Odense and Rigshospitalet, Denmark) counter. Twenty-four of these infants developed moderate to severe respiratory distress syndrome (RDS). The best cut-off value was 8000/μL with a sensitivity of 75% and a specificity of 72%. Forty-four of the 70 aspirates from 2004 to 2005 were analysed by Sysmex, Advia 120 and Cell-Dyn 4000. Thirteen other aspirates from 2004 to 05 were analysed by Sysmex and Coulter Counter LH755. Using Advia and Coulter the results were similar to Sysmex, but LBC obtained with Cell-Dyn were not correlated with the development of RDS. Lamellar body counts on gastric aspirate is a promising tool for prediction of development of RDS in infants of <30 weeks` gestation.
We have investigated seven patients with the type B form of pyruvate carboxylase (PC) deficiency.... more We have investigated seven patients with the type B form of pyruvate carboxylase (PC) deficiency. Mutation analysis revealed eight mutations, all novel. In a patient with exon skipping on cDNA analysis, we identified a homozygous mutation located in a potential branch point sequence, the first possible branch point mutation in PC. Two patients were homozygous for missense mutations (with normal protein amounts on western blot analysis), and two patients were homozygous for nonsense mutations. In addition, a duplication of one base pair was found in a patient who also harboured a splice site mutation. Another splice site mutation led to the activation of a cryptic splice site, shown by cDNA analysis.All patients reported until now with at least one missense mutation have had the milder type A form of PC deficiency. We thus report for the first time two patients with homozygous missense mutations with the severe type B deficiency, clinically indistinguishable from other patients with type B form of PC deficiency.The mutations found here are novel; it is noteworthy that four Turkish patients did not have any mutations in common, despite the rarity of PC deficiency. There is thus no evidence for recurrent mutations in the Turkish or other populations.
Metaphyseal chondrodysplasia (MCD) is a heterogeneous group of diseases characterised by defectiv... more Metaphyseal chondrodysplasia (MCD) is a heterogeneous group of diseases characterised by defective enchondral ossification, leading to metaphyseal changes. The different types of MCD can be distinguished by clinical findings, radiology and genetic tests. Based on a case story with MCD, pancreatic insufficiency and granulocytopenia (Shwachman's syndrome), we review the most common types of MCD with regard to clinical manifestations, radiological findings, and genetic background.
The medical records were reviewed for 109 children (0-15 years) who were investigated by abdomina... more The medical records were reviewed for 109 children (0-15 years) who were investigated by abdominal ultrasonography as part of the evaluation of recurrent abdominal pain. We characterised this group of children in an attempt to localise the characteristics that would predict abnormal findings by abdominal ultrasonography. We conclude that neither location, frequency or duration of pain, nor sex nor age have any predictive value. All abnormal findings seen by abdominal ultrasonography could have been revealed by a carefully taken history, thorough clinical examination and commonly performed laboratory tests, such as urine analysis. We recommend that abdominal ultrasonography should only be used in the evaluation of recurrent abdominal pain in children if there are other characteristics, such as a history of cystitis.
We randomised 59 children hospitalized for croup to treatment with either inhaled budesonide or i... more We randomised 59 children hospitalized for croup to treatment with either inhaled budesonide or injected dexamethasone. Group A were treated with two inhalations of 1000 micrograms budesonide and group B received dexamethasone 0.6 mg/kg intramuscularly. We used a modified Westley-score, based on chest-wall retractions, barking cough, respiratory frequency and stridor. The children was aged three months to six years (mean 20 months). Three hours after the first treatment there was significant improvement in score amongst all children (p < 0.001), but no difference between the two groups (p < 0.20). Six and 12 hours after the first treatment there were significantly better clinical scores in group B (p = 0.001, p = 0.0004). Based on this study we recommend dexamethasone 0.6 mg/kg intramuscularly for children to be treated for croup.
Omphalitis is a serious condition with important morbidity and mortality, especially in developin... more Omphalitis is a serious condition with important morbidity and mortality, especially in developing countries. The most commonly involved micro-organisms are Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. We describe a Danish patient with cellulitis, severe septicaemia, and portal vein thrombosis as fatal complications of omphalitis. In spite of early recognition and prompt treatment in this case, it was not possible to save the child.
Associations between the genetic variation within or downstream of the surfactant protein-D-encod... more Associations between the genetic variation within or downstream of the surfactant protein-D-encoding gene (SFTPD), which encodes the collectin surfactant protein-D (SP-D) and may lead to respiratory distress syndrome or bronchopulmonary dysplasia, recently were reported. Our aim was to investigate whether SFTPD variations affect serum SP-D levels in infants and pulmonary outcome in premature infants. Serum SP-D levels were measured in 211 mature and 202 premature infants, and 7 SFTPD single-nucleotide polymorphisms (SNPs) were genotyped. SNP analysis and haplotype analysis were used to associate genetic variation to SP-D, respiratory distress (RD), oxygen requirement, and respiratory support. The 5'-upstream SFTPD SNP rs1923534 and the 3 structural SNPs rs721917, rs2243639, and rs3088308 were associated with the SP-D level. The same SNPs were associated with RD, a requirement for supplemental oxygen, and a requirement for respiratory support. Haplotype analyses identified 3 hapl...
To describe physical outcome and school performance in a cohort of very-low-birthweight infants t... more To describe physical outcome and school performance in a cohort of very-low-birthweight infants treated with early nasal continuous positive airway pressure (NCPAP)/minimal handling regimen with permissive hypercapnia, in comparison to siblings of normal birthweight. Neonatal and follow-up data from 213 very-low-birthweight infants from 1983-1988 were registered and a questionnaire concerning school achievements was sent to the families of survivors and siblings attending school. Mortality was 22%. Of the survivors, 4% had moderate-severe and 9% mild sequelae. Eighty-seven per cent of VLBW children and 95% of their siblings attended regular school. Average or above-average achievement was accomplished by 33 (65%) of the VLBW children and 34 (74%) of the siblings in mathematics, and 35 (69%) and 32 (68%), respectively, in reading/spelling. None of these differences reached statistical significance. However, the performance ratings correlated significantly with socio-economic conditions. In this study of infants treated with a regimen of early NCPAP/minimal handling, we found a relatively low incidence of handicaps and impairments. Nearly 90% attended ordinary schools, with near-average performances in mathematics and reading/spelling, which were not statistically different to their siblings. The overall results indicate that these infants fare at least as well as survivors after conventional treatment.
To develop a rapid method for diagnosing lung maturity at birth with the purpose of administering... more To develop a rapid method for diagnosing lung maturity at birth with the purpose of administering surfactant early to infants with immature lungs and to spare infants with mature lungs from this treatment. Lamellar body counts (LBC) on gastric aspirates from 191 newborns were counted in the platelet window in automatic blood cell counters. A preliminary study was performed on 108 aspirates from 2000 in infants with <32 weeks' gestation. Furthermore, 83 aspirates from 2004 to 2005 in infants with <30 weeks' gestation were analysed. Lamellar bodies in gastric aspirate were identified by electron microscopy. Seventy of the aspirates from 2004 to 2005 were analysed with a Sysmex XE-2100 (Sysmex, Holbaek, Naestved, Odense and Rigshospitalet, Denmark) counter. Twenty-four of these infants developed moderate to severe respiratory distress syndrome (RDS). The best cut-off value was 8000/μL with a sensitivity of 75% and a specificity of 72%. Forty-four of the 70 aspirates from 2004 to 2005 were analysed by Sysmex, Advia 120 and Cell-Dyn 4000. Thirteen other aspirates from 2004 to 05 were analysed by Sysmex and Coulter Counter LH755. Using Advia and Coulter the results were similar to Sysmex, but LBC obtained with Cell-Dyn were not correlated with the development of RDS. Lamellar body counts on gastric aspirate is a promising tool for prediction of development of RDS in infants of <30 weeks` gestation.
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