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- Björkman, Kristoffer, et al.
(författare)
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Clinical course of patients with single large-scale mtDNA deletions and childhood onset anemia
- 2022
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Ingår i: 14th European Paediatric Neurology Society Congress, Glasgow, UK (ISBN 978-3-00-072065-9).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To add to our knowledge of the clinical spectrum of patients with single large-scale mitochondrial DNA (mtDNA) deletion and childhood onset anemia. Methods: Retrospective collection of clinical data from medical records for patients, both living and deceased, with a single large-scale mtDNA deletion from seven mitochondrial disease centers in five countries. Statistical analysis with descriptive methods and Kaplan-Meier survival analysis. Results: Seventeen patients matching the genetic criterium and with anemia onset before six years of age. Exocrine pancreatic insufficiency was only seen in five patients in this group. Multiple organs were involved in all patients, with the most common non-hematologic ones being skeletal muscle, central nervous system, endocrine, eyes, gastrointestinal system, kidneys, hearing, liver and heart. Psychomotor retardation was seen in ten patients, hearing impairment in nine patients, failure to thrive in eight patients. Eight later developed Kearns-Sayre syndrome. Eleven patients were deceased, with a median age at death of 7.5 years. Conclusions: The classically described phenotype of patients with large-scale mtDNA deletions and early onset anemia is Pearson marrow-pancreas syndrome, characterized by sideroblastic anemia and exocrine pancreas dysfunction. Only a minority of our patients fulfill the original criteria of Pearson syndrome though. Involvement of other organs than the pancreas is more common. The clinical course vary, but multi-system impact is the rule and life-expectancy is low. Early onset anemia in patients with large-scale mtDNA deletions is most frequently not associated with exocrine pancreas dysfunction. Better knowledge of the phenotype is helpful for diagnosis and more accurate prognosis.
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| 2. |
- Decker, Ralph, 1968, et al.
(författare)
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Case report of a girl with secondary amenorrhea associated with aurantiasis cutis
- 2016
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: --- Aurantiasis cutis is a condition of yellowish or golden skin discoloration that can result from eating excessive amounts of foods containing carotene leading to hypercarotenemia(1), described causing secondary amenorrhea(2). Objective & hypothesis: --- Hypercarotenemia can cause secondary amenorrhea without overconsumption of excessive quantities of carotene. Results: --- Laboratory tests showed a ß-Carotene level more than the 2-fold above the upper reference level. Hyperbilirubinemia could be excluded. Hypogonadotropic hypogonadism was not present. There was no evidence for adrenal dysfunction. Liver function tests were normal. Material/ Methods: --- A 16-year-old girl presented to our endocrine outpatient clinic with a 2-year history of varying yellow discoloration of her skin and secondary amenorrhea. The findings of the general physical examination were normal, but there was a marked yellow discoloration of the palms, soles, and nasolabial folds. A dietary history revealed a low carotene diet, but also a low carbohydrate diet. BMI was 19.9 kg/m² (-0.2 SDS) without signs of anorexia. Discussion: --- In this girl we observed hypercarotenemia associated with secondary nonhypothalamic amenorrhea in absence of excess external intake of carotenes. This suggests an intrinsic reason due to a polymorphism(3) in ß-carotene 15,15'-monooxygenase (BCO)(4), an enzyme breaking down carotenes to vitamin A(5). Phenotype-genotype association studies are needed to confirm this hypothesis. Conclusion: --- Secondary non-hypothalamic amenorrhea can be associated with hypercarotenemia. References: --- 1. Tanikawa K, Seta K, Machii A, Itoh S 1961 [Aurantiasis cutis due to overeating of dried laver (nori): a case report]. Jpn J Med Sci Biol 50:414-419 2. Kemmann E, Pasquale SA, Skaf R 1983 Amenorrhea associated with carotenemia. JAMA 249:926-929 3. Leung WC, Hessel S, Meplan C, Flint J, Oberhauser V, Tourniaire F, Hesketh JE, von Lintig J, Lietz G 2009 Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB j 23:1041-1053 4. Frumar AM, Meldrum DR, Judd HL 1979 Hypercarotenemia in hypothalamic amenorrhea. Fertil Steril 32:261-264 5. Lindqvist A, Andersson S 2002 Biochemical properties of purified recombinant human beta-carotene 15,15'-monooxygenase. J Biol Chem 277:23942-23948
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| 4. |
- Seoane, Fernando, et al.
(författare)
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Slightly superior performance of bioimpedance spectroscopy over single frequency regression equations for assessment of total body water.
- 2015
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Ingår i: Engineering in Medicine and Biology Society (EMBC), 2015 37th Annual International Conference of the IEEE. 25-29 Aug. 2015, Milan, Italy.. - : IEEE. - 1094-687X .- 1558-4615. - 9781424492718 - 9781424492701 ; 2015, s. 3707-10
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Konferensbidrag (refereegranskat)abstract
- Electrical bioimpedance has been used for several decades to assess body fluid distribution and body composition by using single frequency and bioimpedance spectroscopic (BIS) techniques. It remains uncertain whether BIS methods have better performance compare to single frequency regression equations. In this work the performance of two BIS methods and four different 50 kHz single frequency prediction equations was studied in a data set of wrist-to-ankle tetrapolar BIS measurements (5-1000 kHz) together with reference values of total body water obtained by tritium dilution in 92 patients. Data were compared using regression techniques and Bland-Altman plots. The results of this study showed that all methods produced similarly high correlation and concordance coefficients, indicating good accuracy as a method. Limits of agreement analysis indicated that the population level performance of Sun's prediction equations was very similar to the performance of both BIS methods. However, BIS methods in practice have slightly better predictive performance than the single-frequency equations as judged by higher correlation and the limits of agreement from the Bland-Altman analysis. In any case, the authors believe that an accurate evaluation of performance of the methods cannot be done as long as the evaluation is done using Bland-Altman analysis, the commonly accepted technique for this kind of performance comparisons.
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| 5. |
- Decker, Ralph, 1968, et al.
(författare)
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Early increase of the bone formation marker PINP is in a higher degree related to growth response compared to bone mineralization in GH treated prepubertal children
- 2015
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Ingår i: Horme Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 84:Suppl 1
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: It has been reported that short-term increases of the bone formation markers intact amino-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BALP) and osteocalcin display different temporal patterns. In adults, the biphasic model of GH action in bone remodelling shows that GH treatment results initially in an increased bone resorption with a concomitant bone loss, which later on is followed by increased bone formation. In children, little is known how bone remodelling takes place. Objective and hypotheses: Bone formation markers reflect different events during osteogenesis, and respond with different time courses during anabolic GH treatment. Method: The study population comprised 128 short prepubertal children (age range 3−11 years; 90 boys, 38 girls) who participated in a longitudinal, prospective, multicenter study in individual GH dosing1, TRN 98-0198-003. The investigated children had either normal or reduced levels of GH secretion. Data from the first 2 years of GH treatment were analyzed. The bone markers were measured using the IDS-iSYS automatic system (Immunodiagnostic Systems)2. The DXA derived variable bone mineral density (BMD) was measured by Lunar DPX-L or Lunar Prodigy. Results: The bone markers PINP, BALP, osteocalcin and 25-hydroxyvitamin D (25(OH)D) at start and deltaPINP at 3 months of GH treatment explained 63% of the growth response at 2 years (p<0.0001), while only 26% of the variation in BMD response after 2 years of treatment was explained (p<0.0001). Conclusion: Bone markers at start of GH treatment, and the 3 months increase of PINP were associated with both growth response and bone mineralization after 2 years of treatment, but with different magnitude of impact on these anabolic GH effects.
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| 6. |
- Decker, Ralph, 1968, et al.
(författare)
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Trans-location of different CYP21A2 mutations in a family with late-onset congenital adrenal hyperplasia (CAH) : Compound CYP21A2-gene mutations in late-onset CAH
- 2017
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Ingår i: JA-PED Meeting 17-19 Nov 2017 (German Paediatric Endocrine Society).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is caused by different mutations in the CYP21A2-gene. To confirm if the symptoms of a heterozygous 21-hydroxylase deficiency are due to a trans- or a cis-location of the different mutations. The patient was a 18-year-old adolescent female. She presented with hirsutism with 26/48 scores of the Ferriman-Gallwey scoring system. At the age of 16, she presented with oligomenorrhea. We detected a hyperandrogenemia (testosterone 2.42 nmol/L; reference 0.29 - 1.67), slightly elevated serum 17-OH-progesterone (17-OHP) levels (2.4 μg/L; reference follicle phase 0.32 – 1.47 μg/l), normal ACTH and plasma renin. No signs of cortisol deficiency (serum early morning cortisol 378 nmol/L; reference 6-10 h: 133 - 537 nmol/L) or salt-wasting were present. ACTH-testing revealed a sufficient cortisol response after 60 min. (645 nmol/L; reference >550 nmol/L) but a substantial increase of 17-OHP (6.2 µg/L; reference <2.6 µg/L), indicating a heterozygous 21-hydroxylase deficiency. The heterozygous mutations were confirmed by DNA sequence analysis of the CYP21A2-gene in this family: 1.) Mother - heterozygous Val281Leu (1). She is a conductor of the late-onset CAH. 2.) Father - IVS2-13A>G (2) and Pro453Ser (3), on the same allele and c.*13G>A on the other allele. He is conductor of the late-onset CAH and the classical CAH at the same time. Both parents have no complains and show no signs of CAH. The mutations in all three children are positioned in trans-locations, consistent with late-onset CAHs: 3.) 18-yo index patient inherited one allele with Val281Leu (maternal) and the other allele with c.*13G>A (paternal). He is conductor of the late-onset CAH and the classical CAH at the same time. 4.) Her 17-yo brother – on one allele IVS2-13A>G and Pro453Ser (paternal) and the other allele Val281Leu (maternal). 5.) Her 12-yo brother Val281Leu and c.*13G>A. Genetic testing confirmed the suspected diagnosis late-onset CAH in our patient as well as in her siblings due to trans-locations of different mutations of the CYP21A2-gene. The wife of the 17-yo brother became pregnant recently. The fetus in the 10th gestational week is at risk to inherit both the classical CAH and late-onset CAH. Examinations of families with late-onset CAH and genetic counseling is mandatory in order to evaluate compound heterozygosity.
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| 9. |
- Smith, SR, et al.
(författare)
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The effect of orlistat 60 mg on changes in body composition over a 24 week treatment: a randomized, placebo-controlled, multicenter study
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: A paucity of data exists on the effects of 60 mg orlistat on changes in body composition, particularly visceral adipose tissue (VAT). Methods: Overweight and obese adults (BMI 25–34.9) with a waist circumference >88 cm (women) or >102 cm (men) were randomized to either orlistat 60 mg (n = 61) or placebo (n = 62) tid for 6 months to examine changes in body composition. Subjects were encouraged to maintain a hypocaloric (-500 kcals/day), low fat (30% calories from fat) diet and were encouraged to exercise. Change from baseline for VAT (kg) by CT was examined at 12 and 24 weeks by ANCOVA. Change from baseline in total fat mass (FM) by EchoMRI, body weight, and waist circumference were examined across multiple time points beginning at week 2 using repeated measure analysis. Results: Mean changes from baseline for all variables were significant in both groups. VAT reduction was greater with orlistat compared to placebo at 12 (LS mean ± SE; )0.50 ± 0.06 vs. )0.32 ± 0.06, P < 0.05) and 24 weeks ()0.62 ± 0.08 vs. )0.32 ± 0.08 P < 0.01). A significantly greater reduction was observed over the 24 weeks in the orlistat group for FM and body weight, as compared to placebo (Group effect P < 0.05), but not waist circumference. Conclusion: Orlistat 60 mg provided significantly greater reductions in weight, FM and VAT across 24 weeks, compared to placebo. The reductions in VAT were relatively stable from 12 to 24 weeks in placebo subjects, whereas VAT reduction in orlistat-treated subjects continued over the 24 week duration.
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| 10. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Significant reduction in body fat assessed by echomri in subjects treated with orlistat 60 mg for 6 months compared with placebo: relationships between changes in body composition and body weight
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: A randomised, double-blind study has demonstrated that orlistat 60 mg is significantly more effective than placebo in reducing visceral fat measured by CT (1). New data from this multicentre study are used to investigate associations between changes in body composition [EchoMRI, total fat mass; body impedance analysis (BIA), % body fat] and body weight. Methods: Adults (BMI 25–34.9 kg/m2) with a waist circumference >88 cm (women) or 102 cm (men) were randomised to receive orlistat 60 mg or placebo, 3x/day for 6 months. A reduced calorie, lower-fat diet was recommended and subjects were encouraged to exercise. Body fat was measured at baseline and weeks 2, 4, 12, and 24. Results: Demographic and baseline characteristics were similar between orlistat 60 mg (n = 62) and placebo (n = 61) groups. Conclusion: Orlistat 60 mg was significantly more effective than placebo in reducing body fat as assessed by EchoMRI and BIA. Change in total fat mass measured by EchoMRI was highly correlated with change in body weight, but the association with weight loss was less marked when measured by BIA (1). Orlistat 60 mg demonstrates a significant reduction in visceral adipose tissue at 24 weeks compared with placebo. Abstract presented at ICAO, Hong Kong, January 2010. Conflict of interest: Investigator, GlaxoSmithKline Consumer Healthcare.
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