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J Häberle

Publications and source records attributed to J Häberle.

17 recordsLinked to original sources
PubMed2005

Misleading diagnosis of partial N-acetylglutamate synthase deficiency based on enzyme measurement corrected by mutation analysis.

UNLABELLED: N-acetylglutamate synthase (NAGS) deficiency is a rare urea cycle disorder. Most of the patients present in the early neonatal period with severe hyperammonaemia and marked neurological impairment. We report on a Turkish family with an index patient, who died due to hyperammonemia, and another three siblings, who received a prophylactic treatment consisting of arginine hydrochloride, sodium benzoate and phenylbutyrate directly after birth. Enzyme measurement in a liver biopsy suggested a diagnosis of partial NAGS deficiency in all three siblings. Thereafter, N-carbamylglutamate was added to the treatment. None of the patients developed hyperammonaemia. After the human NAGS gene was identified, mutation analysis revealed that the consanguineous parents and two siblings were heterozygous for a private mutation (W484R), whereas the wild-type gene was found in the eldest sibling. Therapy was stopped without any deterioration of urea cycle function. CONCLUSION: Diagnosis of partial NAGS deficiency based on enzyme measurement may be misleading and should be completed by mutation analysis.

Acetyltransferases↗
PubMed2003

Gene structure of human carbamylphosphate synthetase 1 and novel mutations in patients with neonatal onset.

Carbamylphosphate synthetase 1 (E.C. 6.3.4.16) deficiency is a rare autosomal recessive disorder of the urea cycle that can result in severe neonatal hyperammonemia. Since the genomic structure of the CPS1 gene was not yet elucidated, mutation detection was performed by analysis of transcripts in the past. Here, we present the entire DNA sequence of the human CPS1 gene including all exon-intron boundaries. Moreover, mutation analysis was performed in six patients leading to the detection of 9 novel mutations including the missense mutations c.2528T>C and c.2623A>G, the nonsense mutations c.712C>T and c.2115ins35bp, the splice site mutations c.1263+5G>C, c.3558+1G>C and c.4101+2T>C, and a small deletion c.3036_3038delGGT. The mutations c.2528T>C and c.2623A>G were identified on a double mutated allele. New data on the genomic structure of the CPS1 gene provided in this study are useful to characterize the heterogenous molecular basis of the disease in patients deficient for carbamylphosphate 1 deficiency.

Age of Onset↗
PubMed2003

Diagnosis of N-acetylglutamate synthase deficiency by use of cultured fibroblasts and avoidance of nonsense-mediated mRNA decay.

Molecular diagnosis of N-acetylglutamate synthase deficiency (NAGSD) has become possible now that the corresponding gene has been identified. We describe the genetic analysis of a patient with NAGSD using low-level transcripts derived from cultured fibroblasts. One defective allele (c.1306-1307insT) was detected by PCR amplification. However, the transcript from a second mutation (IVS3 - 2A>T), causing aberrant splicing with the generation of a premature termination codon, was not detected until interference of nonsense-mediated mRNA decay was abrogated by the translation inhibitor cycloheximide. We demonstrate that low-level transcripts in cells that do not express significant enzyme activity are a valuable tool for molecular studies of genetic alterations, and suggest routine abrogation of nonsense-mediated mRNA decay using cycloheximide when transcript analysis is performed.

Acetyltransferases↗
PubMed2002

Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia.

Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia, an autosomal recessive inherited defect of the urea cycle. Most patients described so far have presented with the classical form of the disease. There are also patients with a mild form of citrullinemia in whom the exact molecular basis and clinical relevance are uncertain. Mutations in the human ASS gene have not yet been described in mildly affected or asymptomatic patients with citrullinemia. The genomic sequence of the human ASS gene is not precisely known making mutation analysis difficult. Here, the entire genomic DNA sequence and mutations in the ASS gene of patients with the classical and mild form of the disease are described. The mutations c.1168G-->A (G390R) and IVS13+5 G-->A and the novel mutation c.323G-->T (R108L) have been found to be associated with classical citrullinemia, whereas the novel mutations c.535T-->G (W179R), and c.1085G-->T (G362V) have been detected on alleles of the mildly affected patients. Thus, mutations found in the human ASS gene of asymptomatic children with biochemical abnormalities and in some cases enzymatically proven citrullinemia have allowed us to classify these cases as ASS-deficient patients. The elucidation of the structure of the human ASS gene has made possible the use of intronic primers for molecular analysis of patients with mild disease and the classical form, and provides another option for prenatal diagnostics in affected families with the severe type.

Amino Acid Sequence↗
PubMed2001

Cervical encephalocele in a newborn--Chiari III malformation. Case report and review of the literature.

Chiari malformations are brain stem anomalies with or without spinal canal involvement. The combination of brain stem and cerebellar anomaly with a cervical cele is named Chiari III malformation. Patients with this extremely rare defect frequently present with severe neurological defects and can have a poor prognosis. Following a report on a newborn child with a Chiari III malformation that took a fatal but typical course the literature is reviewed.

Arnold-Chiari Malformation↗
PubMed2001

Genetic analysis of carbamoylphosphate synthetase I and ornithine transcarbamylase deficiency using fibroblasts.

UNLABELLED: Deficiencies of carbamoylphosphate synthetase or of ornithine transcarbamylase, two urea cycle enzymes located within mitochondria, often present as severe neonatal hyperammonaemic crises and have a poor prognosis. While genetic analysis of the X-chromosomal transmitted ornithine transcarbamylase deficiency (OTC) is performed by exon-wise mutation screening of genomic DNA in most cases, identification of mutations in the autosomal inherited carbamoylphosphate synthetase (CPS 1) deficiency requires analysis of transcripts due to the unknown genomic structure. We tested the hypothesis that CPS 1 and OTC are expressed at low levels in fibroblasts and indeed were able to amplify full-length cDNA from that source. Using a reverse transcriptase polymerase chain reaction based procedure we completely characterised the genetic background in five patients and identified three novel mutations and a novel polymorphism of the CPS 1 gene (deletion/insertion 2170delGCTCinsCCA, nonsense mutation 2359C > T, missense mutation 3161T > G and Thr1406Asn, respectively), as well as the missense mutations 482A > G and 994T > A of the OTC gene. CONCLUSION: Cultured fibroblasts are an easily accessible source for genetic analysis of inborn errors of urea cycle enzymes which are functionally expressed only in liver and gut.

Carbamoyl-Phosphate Synthase (Ammonia)↗
PubMed1999

New strategies in diagnosis and treatment of thrombotic thrombocytopenic purpura: case report and review.

UNLABELLED: The pentad of thrombocytopenia, haemolytic anaemia, mild renal dysfunction, neurological signs and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults but also children have been described with this condition. The disorder may take a relapsing course, termed chronic relapsing TTP (CRTTP), which although very rare, may also begin in childhood. Deficiency of a recently identified enzyme, the von Willebrand factor (vWF)-cleaving protease, seems to play a major role in the development of TTP. We report on a 3-year-old boy with a dramatic but typical clinical course of CRTTP. At the time of diagnosis, neurological deficits and multiple cerebral infarctions had already occurred. In plasma, vWF-cleaving protease was completely absent, both during acute TTP and in remission. There was no protease inhibitor detected. Regular infusions of fresh frozen plasma were successfully given for replacement on a prophylactic basis. CONCLUSION: Assay of von Willebrand factor-cleaving protease helps to diagnose a form of thrombotic thrombocytopenic purpura which may be managed by prophylactic treatment with fresh frozen plasma.

Blood Coagulation Tests↗
PubMed1999

Studying patients with inflammatory back pain and arthritis of the lower limbs clinically and by magnetic resonance imaging: many, but not all patients with sacroiliitis have spondyloarthropathy.

OBJECTIVE: Clinical and magnetic resonance imaging (MRI) data of 170 consecutive patients with inflammatory back pain (IBP) and/or oligoarthritis of the lower limbs were evaluated in a retrospective study. The aim was to determine the frequency of sacroiliitis and spondyloarthropathy (SpA) in this population, and to assess the significance of HLA B27 measurements for diagnosis in early disease. METHODS: Pelvic X-rays were performed in all IBP patients and dynamic MRI of the sacroiliac joints in patients with IBP who had indefinite results on sacroiliac X-rays (n = 32). RESULTS: European Spondyloarthropathy Study Group criteria for SpA were fulfilled by 106/170 patients (62.4%); eight additional patients had symptoms suggestive of SpA (4.7%). The most frequent SpA subset was undifferentiated SpA (uSpA), diagnosed in 46/106 patients (43.4%). Sacroiliitis was detected by MRI in 21/32 patients with IBP and unclear X-rays (65.6%). Of those, 14 were diagnosed as SpA and seven females with moderate unilateral sacroiliitis, but no features of SpA, also not on follow-up (at least 1 yr), were classified as undifferentiated sacroiliitis (US). Ten of the 14 SpA (71.4%) and none of the seven US patients were HLA B27 positive. CONCLUSION: HLA B27 positivity in IBP patients with MRI-proven sacroiliitis positively predicts SpA. uSpA is a frequent SpA subset. There are HLA B27-negative non-SpA patients with moderate unilateral sacroiliitis whom we propose to be classified as US.

Adult↗
PubMed1997

Nested polymerase chain reaction strategy simultaneously targeting DNA sequences of multiple bacterial species in inflammatory joint diseases. II. Examination of sacroiliac and knee joint biopsies of patients with spondyloarthropathies and other arthritides.

OBJECTIVE: Bacteria play a crucial pathogenetic role in reactive arthritis (ReA) and other forms of spondyloarthropathy (SpA) and in Lyme arthritis. Although there is evidence of local persistence of bacterial antigens no definitive method revealing microbes in peripheral joints has been established. We detected DNA of individual bacteria in synovial material by PCR. Applying molecular technology we screened simultaneously for 8 bacterial genomes in arthritis and sacroiliitis. METHODS: Sacroiliac (SI) biopsy specimens taken from the SI joint of 8 patients with ankylosing spondylitis (AS, n = 5) and undifferentiated SpA (uSpA, n = 3) by computed tomography guided biopsy were investigated for presence of bacterial DNA. Similarly, synovial membrane samples obtained by office arthroscopy from 15 patients with ReA (n = 5), uSpA (n = 3), undifferentiated oligoarthritis (uOligo, n = 3), and rheumatoid arthritis (RA, n = 4) were screened. Nested PCR was performed for DNA of the following bacteria: Chlamydia trachomatis, C. pneumoniae, Yersinia enterocolitica, Salmonella enteritidis, Campylobacter jejuni, Shigella flexneri, Klebsiella pneumoniae, and Borrelia burgdorferi. RESULTS: No bacterial DNA was found in the SI biopsies of patients with uSpA and AS. DNA of B. burgdorferi (n = 2) and C. trachomatis (n = 1) was detected in 3 patients with uOligo, but not in patients with ReA or RA. DNA of other microbes including K. pneumoniae was not found. Patients' mean disease duration was 5.3 years (2 mo-8.4 yrs). CONCLUSION: We found bacterial DNA in peripheral joints of patients with uOligo, while in patients with ReA, AS, and uSpA no bacterial DNA was detected in peripheral or SI joints. The failure to detect bacterial DNA in patients with SpA suggests autoimmune mechanisms operate in later stages of disease.

Adult↗
PubMed1992

[Stent-supported percutaneous therapy of iliac vein stenosis following operative thrombectomy and placement of a shunt].

Among 15 patients with acute thrombotic disease of pelvic veins who had been submitted to operative thrombectomy and creation of arteriovenous fistula in the groin, 12 presented with stenotic lesions 3 months later. These stenoses were submitted to percutaneous angioplasty. If angioplasty failed, percutaneous placement of a vascular stent (wall stent) was performed immediately (n = 7). Stenting in cross-over-technique proved practicable in all cases. Secondary stenotic disease in the exclusively dilated area was observed in 3/5 cases and was also treated with a wall stent. In one patient with recurrent stenoses who refused stenting, extended thrombosis occurred after occlusion of the AV-fistula. At mid-term PTA was successful in only two cases. Intimal hyperplasia was observed in only one wall stent treated patient. Percutaneous treatment of iliacal stenoses in patients with postthrombotic syndrome may be performed safely under the protective effect of the fistula. With the presented technique, patency of pelvic veins could be restored in 11/12 patients with postoperative significant venous stenoses.

Adult↗
PubMed1992

[Malignant fibrous histiocytoma: productive use of imaging procedures].

Malignant fibrous histiocytoma (MFH) of soft tissue is a rare tumor. We present a case of MFH in the bicipital muscle. Local muscle hypertrophy or lesions of the long tendon of the bicipital muscle may be a difficult differential diagnosis. This case is used for outlining advantages of ultrasound, computed tomography and magnetic resonance imaging. In conventional radiography MFH is seen as a soft-tissue tumor sometimes involving the bone. CT is the best way to test bone involvement. Tumor extension will be assessed with great accuracy by means of ultrasonics and magnetic resonance imaging (MRI).

Arm↗
PubMedDate not supplied

[Thrombocytic alpha-delta-storage-pool-disease: shortening of bleeding time after infusion of 1-desamino-8-D-arginine vasopressin].

BACKGROUND: The synthetic vasopressin derivate desmopressin (1-desamino-8-D-arginine vasopressin) has been reported to shorten the bleeding time in patients with hemophilia A, von Willebrand's disease and several functional platelet disorders. In addition to substitution of platelets, vasopressin is therefore used to prevent bleeding complications. CASE: We report the case of a 14-year-old female patient with prolonged bleeding time due to the rare thrombocytic alpha-delta-storage-pool-disease. When normal donor platelet substitution alone was ineffective, bleeding time was normalised after infusion of desmopressin and elective wisdom-tooth extraction was performed without significant postoperative bleeding. DISCUSSION: Infusion of desmopressin appears to be effective in shortening bleeding time in thrombocytic storage-pool-disease. Its use could prevent bleeding complications after trauma and surgical interventions and may possibly help to spare the need for platelet concentrates.

Adolescent↗
PubMedDate not supplied

CT-guided intraarticular corticosteroid injection into the sacroiliac joints in patients with spondyloarthropathy: indication and follow-up with contrast-enhanced MRI.

PURPOSE: Our goal was to prospectively study the therapeutic efficacy of CT-guided intraarticular corticosteroid instillation of inflamed sacroiliac joints (SIJs) in patients with spondyloarthropathies and to evaluate the role of MRI as a procedure for establishing the indication and for therapeutic follow-up. METHOD: A total of 103 CT-guided corticosteroid injections of the SIJs were performed in 66 patients with inflammatory back pain (IBP): 37 bilateral, 29 unilateral. All patients did not respond to an immediately preceding 4 week nonsteroidal antiinflammatory therapy. Forty milligrams of a crystalline long-acting corticoid was instilled in each joint. All 66 patients underwent continuous clinical follow-up at 10 to 12 week intervals after corticosteroid injection to a maximum of 18 months. The degree of subjective complaints before and after the intervention was recorded using a analogue scale (0 = no pain, 10 = unbearable pain). Dynamic contrast-enhanced (Gd-DTPA, 0.1 mmol/kg body wt) MRI with quantitative determination of contrast enhancement was performed in all patients before the therapeutic intervention and in 38 patients at 8 +/- 4 months. RESULTS: Sixty-one of the 66 study patients (92.5%) showed a statistically significant abatement of subjective complaints from 8.8 +/- 1.3 to 3.3 +/- 2.3 (p < 0.01) at 1.7 +/- 1.1 weeks after intervention, and this improvement lasted for 10 +/- 5 months. The percentage contrast enhancement at dynamic MRI likewise showed a significant reduction from 100.3 +/- 48% before to 44.3 +/- 36.1% after intraarticular cortisone administration (p < 0.01). CONCLUSION: CT-guided intraarticular corticosteroid instillation in the SIJs may be regarded as an effective therapy for florid sacroiliitis. The severity of inflammation and the response to therapy can be determined quantitatively by dynamic MRI.

Adult↗