Proteome profiling of formalin-fixed paraffin-embedded (FFPE) specimens has gained traction for the analysis of cancer tissue for the discovery of molecular biomarkers. However, reports so far focused on single cancer entities, comprised relatively few cases and did not assess the long-term performance of experimental workflows. In this study, we analyze 1220 tumors from six cancer entities processed over the course of three years.
View Article and Find Full Text PDFNewborn screening (NBS) allows early identification of individuals with rare disease, such as isovaleric aciduria (IVA). Reliable early prediction of disease severity of positively screened individuals with IVA is needed to guide therapeutic decision, prevent life-threatening neonatal disease manifestation in classic IVA and over-medicalization in attenuated IVA that may remain asymptomatic. We analyzed 84 individuals (median age at last study visit 8.
View Article and Find Full Text PDFAstrocytes are highly abundant in the mammalian brain, and their functions are of vital importance for all aspects of development, adaption, and aging of the central nervous system (CNS). Mounting evidence indicates the important contributions of astrocytes to a wide range of neuropathies. Still, our understanding of astrocyte development significantly lags behind that of other CNS cells.
View Article and Find Full Text PDFObjective: To study the impact of the quality of therapeutic control on fertility and on the prevalence of testicular adrenal rest tumours (TART) in young males with congenital adrenal hyperplasia (CAH).
Design: Combined cross-sectional and retrospective clinical study.
Methods: Twenty-nine patients and age-matched controls underwent clinical investigation, including semen analysis, testicular and adrenal ultrasound imaging, and serum and hair steroid analysis.
Isovaleric aciduria (IVA), a metabolic disease with severe (classic IVA) or attenuated phenotype (mild IVA), is included in newborn screening (NBS) programs worldwide. The long-term clinical benefit of screened individuals, however, is still rarely investigated. A national, prospective, observational, multi-center study of individuals with confirmed IVA identified by NBS between 1998 and 2018 was conducted.
View Article and Find Full Text PDFBackground And Objectives: Growth is an important criterion to evaluate health in childhood and adolescence, especially in patients depending on special dietary treatment. Phenylketonuria (PKU) is the most common inherited disease of amino acid metabolism. Patients with PKU depend on a special phenylalanine-restricted diet, low in natural protein.
View Article and Find Full Text PDFBackground: Impaired glucose tolerance and type 2 diabetes are well-known features in patients with Turner syndrome. To the best of our knowledge, there is only one reported case of hyperinsulinemic hypoglycemia associated with a complex mosaic Turner syndrome available in the current literature.
Patient: We report on the case of a 13-month-old girl with a complex mosaic Turner genotype and mild hyperinsulinemic hypoglycemia responsive to diazoxide therapy.
Background: Transition from pediatric to adult health care is a particularly vulnerable period for patients with inborn metabolic diseases. Aim of the present study was to evaluate the current transition situation of patients with phenylketonuria (PKU) in Leipzig, Germany, by analysis of the medical care, metabolic control, patients' satisfaction, socio-economic and psychosocial status, in order to identify areas of weakness and potential improvement.
Methods: Patients who had been transferred from pediatric to adult medical care between 2005 and 2008 were identified.
Autosomal-dominant brachydactyly type E (BDE) is a congenital limb malformation characterized by small hands and feet predominantly as a result of shortened metacarpals and metatarsals. In a large pedigree with BDE, short stature, and learning disabilities, we detected a microdeletion of approximately 900 kb encompassing PTHLH, the gene coding for parathyroid hormone related protein (PTHRP). PTHRP is known to regulate the balance between chondrocyte proliferation and the onset of hypertrophic differentiation during endochondral bone development.
View Article and Find Full Text PDFWien Med Wochenschr
October 2009
We report on a 21-year-old woman with classic phenylketonuria, who presented at our outpatient clinic at week 14 of pregnancy. Despite intensive preconceptional counselling about the risk of raised Phenylalanine (Phe) levels for the offspring and nutritional consultations about the necessity to be on a Phe-restricted diet she had elevated blood Phe concentrations. Phe level could be lowered to the recommended range during a stay as an inpatient, but the patient was not able to maintain the recommended levels due to non-compliance.
View Article and Find Full Text PDFContext: The LHX4 LIM-homeodomain transcription factor has essential roles in pituitary gland and nervous system development. Heterozygous mutations in LHX4 are associated with combined pituitary hormone deficiency.
Objectives: Our objectives were to determine the nature and frequency of LHX4 mutations in patients with pituitary hormone deficiency and to examine the functional outcomes of observed mutations.
The LHX3 and LHX4 LIM-homeodomain transcription factors play essential roles in pituitary gland and nervous system development. Mutations in the genes encoding these regulatory proteins are associated with combined hormone deficiency diseases in humans and animal models. Patients with these diseases have complex syndromes involving short stature, and reproductive and metabolic disorders.
View Article and Find Full Text PDFX-linked adrenal hypoplasia congenita (AHC) is a rare developmental disorder associated with primary adrenal insufficiency and combined primary and secondary male hypogonadism. It is caused by deletions or mutations of the NR0B1 (DAX1) gene encoding DAX1, an atypical orphan member of the nuclear receptor superfamily. The continuous molecular genetic analysis of male patients with primary adrenal insufficiency revealed 13 novel mutations within the coding region of the NR0B1 gene which are predicted to inactivate the DAX1 function.
View Article and Find Full Text PDFMutations in the PROP1 gene are the most frequent genetic defects in patients with combined pituitary hormone insufficiency. However, controversy exists about the timing and extent of pituitary insufficiency, and it remains unclear whether adrenal failure is a typical feature of this condition. We performed a retrospective longitudinal analysis of nine patients with PROP1 mutations who were under medical supervision at our clinic for 15.
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