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Biomedical subjects

W H Hörl

Publications and source records attributed to W H Hörl.

At least 19 recordsLinked to original sources
PubMed2002

Contribution of anaemia to progression of renal disease: a debate.

It is hypothesized that anaemia contributes to the progression of renal disease via hypoxia and oxidative stress. These effects may stimulate the production of extracellular matrix by fibroblasts, increasing interstitial fibrosis and leading to tubular destruction. Recombinant human erythropoietin (r-HuEPO, epoetin) has antioxidative and anti-apoptotic properties, though these effects have yet to be demonstrated in renal cells. In theory, epoetin treatment might slow the progression of renal failure, not only by correcting anaemia but also via direct effects on tubular and vascular cell survival. Alternative hypotheses suggest, however, that epoetin could have negative effects on the kidney because of its vasoconstrictive action, which is independent of haemoglobin levels. Retrospective and prospective clinical studies clearly show that epoetin does not accelerate progression of renal disease, provided that blood pressure is well controlled. Some studies suggest that epoetin slows the progression of renal failure, although this remains a controversial issue, as all these studies have methodological limitations. Larger randomized controlled trials and meta-analysis of the existing trials are required to establish whether treatment of anaemia with epoetin can indeed slow the progression of renal disease.

Anemia↗
PubMed2001

N-terminal fragments of the proatrial natriuretic peptide in plasma and urine of kidney graft recipients.

BACKGROUND: Successful kidney transplantation normalizes elevated proatrial natriuretic peptide (proANP) plasma concentrations of renal failure patients in the early posttransplant period. We evaluated plasma and urinary proANP fragments in the late posttransplant period. METHODS: Immunoreactive proANP(1-30) and proANP(31-67) were determined in 389 renal transplant (Rtx) recipients in the long-term, follow-up period and in 16 healthy controls. RESULTS: Rtx recipients had significantly higher concentrations of proANP(1-30) and proANP(31-67) in both plasma and urine than healthy controls. Although their graft function was normal, all of these long-term Rtx recipients were taking glucocorticoids, which increase proANP(1-30) and proANP(31-67) in the circulation to the extent found in this investigation. Two-thirds of these recipients were also taking cyclosporine, which also increases atrial peptides. Urinary proANP(31-67) was significantly higher than urinary proANP(1-30); 5.5-fold in Rtx patients and 2-fold in controls. Deterioration of renal graft function was associated with a rise of plasma proANP(1-30) from 0.98+/-0.66 to 6.28+/-3.55 nmol/l (P<0.0001) and plasma proANP(31-67) from 1.81+/-1.04 to 7.89+/-3.76 nmol/l (P<0.0001). Urinary excretion of proANP(1-30) increased from 0.27+/-0.34 to 5.96+/-5.07 nmol/24 hr (P<0.0001) and proANP(31-67) from 1.45+/-0.85 to 12.23+/-5.12 nmol/24 hr (P<0.0001). Also proteinuria enhanced plasma and urinary proANP fragments. CONCLUSIONS: ProANP(1-30) and proANP(31-67) of Rtx recipients are affected by immunosuppression, hypertension, renal failure, and proteinuria. One would have expected proANP(1-30) and proANP(31-67) not to normalize because of the glucocorticoids that they were receiving.

Adult↗
PubMed2001

Serum proteins modified by neutrophil-derived oxidants as mediators of neutrophil stimulation.

Reactive oxygen intermediates (ROI) released during inflammation may act as important mediators of neutrophil effector functions. The objective of this investigation was to evaluate the influence of ROI generation on neutrophil adhesion molecule regulation and degranulation. Induction of the neutrophil oxidative burst via Fcgamma receptor cross-linking was accompanied by up-regulation of neutrophil surface CD11b, CD35, and CD66b only in the presence of selected serum proteins, such as purified human C4, C5, or human serum albumin (HSA). Scavenging of ROI attenuated protein-dependent receptor regulations. Moreover, exogenous hydrogen peroxide was effective to increase neutrophil CD11b expression in a protein-dependent way. HSA exposed to neutrophil-derived ROI displayed signs of oxidative modification in terms of carbonyl formation. Such modified HSA transferred to resting neutrophils bound readily to the cell surface and effected receptor modulation as well as cellular spreading. In contrast, neither native HSA nor HSA protected against oxidation by the tocopherol analog Trolox exhibited agonistic properties. In conclusion, we demonstrate that neutrophil-derived ROI modify selected serum proteins, which, in turn, act as proinflammatory mediators of neutrophil stimulation.

Blood Proteins↗
PubMed2001

Efficacy of folinic versus folic acid for the correction of hyperhomocysteinemia in hemodialysis patients.

The effectiveness of intravenous folinic acid or intravenous folic acid for the treatment of hyperhomocysteinemia of hemodialysis patients is unknown. In a randomized, controlled, double-blind trial, 66 hemodialysis patients were administered either 15 mg of folic acid or an equimolar amount (16.1 mg) of folinic acid intravenously three times weekly. Normalization of total homocysteine (tHcy) plasma levels after 4 weeks of treatment was achieved in 10 patients (30.3%) in the folic-acid group and 6 patients (18.2%; P: = 0.389) in the folinic-acid group (normalization at any time during the study period in 39.4% and 33.3% of the patients; P: = 0.798). The relative reduction in tHcy plasma levels at week 4 was 32.2% in the folic-acid group and 34.1% in the folinic-acid group. A high baseline tHcy plasma concentration (P: = 0.00001), methylenetetrahydrofolate reductase (MTHFR) 677TT/1298AA genotype (P: = 0.03540), and low red blood cell folate concentrations (P: = 0.02285) were associated with a better relative response to treatment. Normalization of tHcy plasma levels was dependent on a lower baseline tHcy level (P: = 0.01976), younger age (P: = 0.00896), and MTHFR 677TT/1298AA or 677CT/1298AC genotypes (P: = 0.00208 and P: = 0.02320, respectively). A 4-week course of intravenous folinic acid is not superior to intravenous folic acid in reducing elevated tHcy plasma levels in hemodialysis patients. The response to treatment is predicted by tHcy plasma level, red blood cell folate content, and MTHFR genotype.

Double-Blind Method↗
PubMed2001

Rapidly progressive glomerulonephritis and carcinoma of the hypopharynx.

We report on a 50-year-old man with rapidly progressive glomerulonephritis and carcinoma of the hypopharynx. Because cancer treatment was followed by remission of proteinuria and complete restoration of renal function, a causal relationship between tumor and glomerular injury seems possible.

Brachytherapy↗
PubMed2001

A case of continuous ambulatory peritoneal dialysis peritonitis with an uncommon organism and an atypical clinical course.

This report describes a 46-year-old patient who experienced an atypical course of peritonitis while undergoing continuous ambulatory peritoneal dialysis (CAPD). The first sign of peritonitis was progressive impairment of ultrafiltration with increasing fluid absorption. The patient came to the center after 5 days with leg edemas and 645 leukocytes/microL in the first dialysate outflow. On the same day, the dialysate cell count decreased to 208/microL. During the following days, ultrafiltration failure persisted despite spontaneous normalization of PD-fluid leukocytes. No other clinical symptoms were observed, and the serum C-reactive protein (CRP) level remained normal. Magnetic resonance peritoneography and abdominal radiograph did not show dislocation of the catheter, a dialysate leak, or other causes of ultrafiltration failure. At day 14, fever, diarrhea, and an elevated serum CRP level occurred. Dialysate cultures taken on days 8, 11, and 14 showed growth of NEISSERIA: sicca. After initiation of antibiotic therapy with levofloxacine on day 14 ultrafiltration, clinical symptoms and serum CRP normalized within 3 days. In conclusion, Neisseria sicca should be considered as a rare cause of PD peritonitis. Our case report further illustrates the importance of ultrafiltration failure as an early and main symptom of peritoneal inflammation. The frequently used peritonitis criteria may not apply to cases of mild PD peritonitis.

C-Reactive Protein↗
PubMed2001

Treatment of coagulation inhibitors with extracorporeal immunoadsorption (Ig-Therasorb).

Coagulation inhibitors may occur as alloantibodies in patients with congenital factor deficiencies or as autoantibodies in patients with a previously normal coagulation. We treated 10 patients with factor VIII inhibitors (three haemophiliacs and seven patients with acquired factor VIII inhibitors) and one patient with a factor V inhibitor using extracorporeal immunoadsorption to immobilized antibodies against human immunoglobulins (Ig-Therasorb). The initial inhibitor titre was between 18 BU/ml and 540 BU/ml. Nine patients had signs of bleeding. Eighty-nine immunoadsorption sessions were performed in the 11 patients (8.1 +/- 5.1 per patient), each processing 6980 +/- 880 ml of plasma in 3.8 +/- 0.5 h. The mean reduction of the inhibitor titre was 71.9 +/- 19.4% per session. Serum IgG, IgA and IgM levels decreased by 68.7 +/- 10.1%, 55.7 +/- 12.7% and 48.6 +/- 11.1% respectively. In two haemophiliac patients, an initial titre reduction prior to an immune tolerance protocol was performed. Another haemophiliac patient was treated because of acute cerebral bleeding. In six out of eight patients with acquired inhibitors, a durable elimination was achieved within a median of 18 d. Treatment was safe and well-tolerated and seems to be a promising method in the treatment of patients with coagulation inhibitors, especially when a fast inhibitor titre reduction is necessary.

Adult↗
PubMed2001

Differential effects of growth hormone therapy in malnourished hemodialysis patients.

BACKGROUND: Malnutrition is common in chronic hemodialysis patients and is associated with increased morbidity and mortality. Several factors such as metabolic acidosis, hyperparathyroidism, and insulin as well as growth hormone (GH) resistance may lead to enhanced protein catabolism. Recombinant human growth hormone (rhGH) has been proposed as treatment of malnutrition because of its anabolic effects. METHODS: In the present placebo-controlled, double blind study, the effects of three months of rhGH therapy on nutritional and anthropometric parameters, on bone metabolism and bone mineral density (BMD), as well as on polymorphonuclear leukocyte (PMNL) function and quality of life (QoL) were evaluated in 19 malnourished hemodialysis patients (10 females and 9 males) with a mean age of 59.3 +/- 13.4 years. RhGH (0.125 IU/kg) was given three times a week during the first four weeks and 0.25 IU/kg thereafter three times a week after each dialysis session. RESULTS: Insulin-like growth factor I (IGF-I) concentration rose significantly from 169.2 +/- 95.6 ng/mL to 262.9 +/- 144.4 ng/mL (p< 0.01) in the group receiving rhGH. Albumin, prealbumin, transferrin, cholesterol, high-density lipoprotein (HDL) cholesterol, cholinesterase, predialytic creatinine, and blood urea nitrogen showed no significant changes during the three months in both groups. Total body fat (%TBF) was slightly reduced after three months (P = NS) in the patients receiving GH, whereas lean body mass (LBM) remained stable during therapy. Procollagen I carboxy terminal peptide (PICP), a marker of bone formation, increased significantly after three months from 250.1 +/- 112.6 to 478.5 +/- 235.2 microg/L (P < 0.01) in the GH-treated patients, whereas parameters of bone resorption like telopeptide ICTP showed only a slight increase (50.3 +/- 18.5 vs. 70.0 +/- 39.5 microg/L, P = NS). BMD at the lumbar spine decreased significantly after three months in the treatment group (0.8 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, P < 0.01), whereas BMD at the femoral neck remained stable in both groups. Phagocytic activity of PMNLs increased significantly after three months of therapy with rhGH, whereas other parameters of PMNL function were not affected by GH. QoL was slightly improved in the GH treated group, but decreased markedly in the placebo group. CONCLUSIONS: Three months of treatment with rhGH in malnourished patients on chronic hemodialysis causes a significant increase in IGF-I levels without significant changes in nutritional and anthropometric parameters. In contrast, bone turnover was enhanced with an initial decrease in BMD at the lumbar spine, and phagocytic activity of PMNLs was increased.

Adult↗
PubMed2001

Plasma concentration and urinary excretion of N-terminal proatrial natriuretic peptides in patients with kidney diseases.

BACKGROUND: Biologically active N-terminal fragments such as proANP(1-30), proANP(31-67), and proANP(1-98) derive from the prohormone of alpha-human atrial natriuretic peptide [proANP(99-126) or alpha-ANP]. No systematic data are available for patients with different kidney diseases. METHODS: Specific immunoassays were developed to determine plasma and urine concentrations of these fragments in 121 patients with different degrees of kidney function and urinary protein excretion, respectively. RESULTS: In patients with kidney disease and normal renal function without proteinuria, circulating proANP(1-30) and proANP(31-67) increased 2.8-fold and 6.5-fold, respectively. Urinary excretion of proANP(31-67) increased by a factor of 7.7 in these patients, whereas proANP(1-30) was not affected. Patients with impaired renal function had a dramatic increase of urinary proANP(31-67) excretion even before serum creatinine levels started to rise. The progression of renal failure caused a significant rise of circulating proANP(1-30) (4.3-fold) and proANP(31-67) (3.0-fold) compared with patients with normal renal function. Urinary excretion of proANP peptides significantly increased, particularly when the serum creatinine level was> 5.0 mg/dL [proANP(1-30) 26-fold, proANP(31-67) 8.4-fold]. Urinary excretion of proANP(1-30) increased up to 4.4-fold and urinary excretion of proANP(31-67) increased up to 2.4-fold in patients with proteinuria in excess of 3 g/24 h. CONCLUSIONS: Plasma concentrations and urinary excretion of proANP(1-30) and proANP(31-67) are affected by kidney disease and function, but not by proteinuria per se. It is proposed that the diseased kidney increases early urinary excretion of proANP fragments to participate in the regulation of renal function as well as sodium and water excretion.

Adolescent↗
PubMed2001

Uremic toxins modulate the spontaneous apoptotic cell death and essential functions of neutrophils.

Clearance of neutrophils via apoptosis from the site of infection is crucial for the coordinated resolution of inflammation. The balance between stimulating and attenuating as well as between pro- and anti-apoptotic factors is necessary for maintenance of an effective immune response without the harmful side effects of neutrophil action. This article describes the effect of glucose-modified serum proteins and of free immunoglobulin light chains (IgLCs) on neutrophil functions and apoptosis. Both groups of proteins are found at elevated levels in sera of uremic patients. Glucose-modified proteins increase both the chemotactic movement of neutrophils and the activation of glucose uptake. Spontaneous neutrophil apoptosis is increased in the presence of these modified serum proteins. On the other hand, the presence of free IgLCs, previously shown to diminish neutrophil chemotaxis and the activation of glucose uptake, increase the percentage of viable neutrophils by inhibiting spontaneous apoptotic cell death. We conclude that both glucose-modified proteins and free IgLCs can be considered to be uremic toxins and both contribute to the disturbed immune function in uremic patients. Their concentrations as well as the microenvironment in which they are acting seem to be important for their actual effects.

Apoptosis↗
PubMed2001

Complement-dependent acceleration of apoptosis in neutrophils by dialyzer membranes.

Recently, we have shown that cuprophan (CU) causes receptor modulation by a C5-dependent mechanism, which is activated by neutrophil-derived reactive oxygen intermediates. The objective of our study was to evaluate the contribution of dialyzer membranes to the induction of apoptosis in human neutrophils [polymorphonuclear cells (PMNs)]. PMNs harvested from healthy donors were incubated with hollow fibers from a biocompatible membrane polysulfone (PS) and a bioincompatible membrane CU, all in the presence of 25% human serum. After 4, 8, and 12 hours of incubation at 37 degrees C, apoptosis was quantitated by counting the numbers of cells showing features of apoptosis on cytospins by light microscopy and also by flow cytometry using propidium iodide nuclear staining. Compared with PMNs incubated with serum alone, cells cultured with fibers of PS demonstrated a higher percentage of apoptosis. Fibers from CU dialyzers led to a more pronounced induction of apoptosis in PMNs, which was significantly higher compared with PS. This effect was partly mediated by heat-sensitive serum products and depended on the presence of divalent cations. In contrast to the recently described C5-dependent pathway in PMN receptor modulation by CU, this effect seemed to depend on the presence of the complement factor C3. In conclusion, our results indicate that besides the well-known accelerated apoptosis of PMNs in uremia, both biocompatible and bioincompatible dialyzer material itself can accelerate apoptosis in human PMNs.

Apoptosis↗
PubMed2001

Recent insights into the molecular genetics of the homocysteine metabolism.

The homocysteine plasma level is determined by non-genetic and genetic factors. In recent years evidence has accumulated that the total homocysteine plasma level of patients under different forms of renal replacement therapy is influenced by a common mutation at nucleotide position 677 of the gene coding for 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T). Furthermore, compound heterozygosity for the 677T allele and a novel A-->C polymorphism at nucleotide position 1298 of MTHFR is suggested to correlate with a decrease of folate plasma concentrations. Because polymorphisms of genes coding for proteins involved in the metabolism of homocysteine may contribute to elevated total homocysteine plasma concentrations, molecular genetic analyses of the homocysteine pathways experienced a drift towards screening for candidate genes with a putative relationship to total homocysteine plasma levels. One example is the cloning of the FOLR1 gene coding for the folate-binding protein (Folbp1), which has recently been inactivated in mice, thus representing an elegant model to investigate the consequence on the homocysteine metabolism. Furthermore, the recent characterization of the CUBN gene encoding the intrinsic factor-vitamin B12 receptor (cubilin) provides a basis to identify the causative mutations in patients suffering from a hereditary syndrome of hyperhomocysteinemia that presents with megaloblastic anemia and proteinuria. This review focuses on recent insights into the molecular genetics of MTHFR, FOLR1, and CUBN, and their relationships to the metabolism of the amino acid homocysteine.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2001

Effect of MTHFR genotypes and hyperhomocysteinemia on patient and graft survival in kidney transplant recipients.

BACKGROUND: The total homocysteine (tHcy) plasma level, which is partly determined by the MTHFR 677C-->T genotype, may be associated with vascular disease. We prospectively examined the influence of MTHFR genotypes (677C-->T, 1298A-->C) and tHcy plasma concentration on all cause mortality and graft outcomes of renal transplant recipients. METHODS: Baseline tHcy plasma levels of 189 patients (three groups with either the MTHFR 677CC, CT or TT genotype, including 63 patients in each group, were matched for age, gender, body mass index and creatinine clearance at baseline), were obtained between September 1996 and May 1997. Follow-up data (time until return to dialysis therapy, time and cause of death) were collected from April to June 1999. Kaplan-Meier survival estimations were calculated and plotted, the groups (three MTHFR 677C-->T genotype groups, or three MTHFR 1298A-->C genotype groups, or two groups with tHcy plasma levels above/below 15 micromol/L) were compared by log-rank test. Age, gender, body mass index (BMI), time since transplantation, serum creatinine, creatinine clearance, combined MTHFR 677C-->T/1298A-->C genotypes, tHcy, folate and vitamin B12 plasma levels were evaluated with regard to graft and patient survival in a multivariate Cox-proportional hazard regression model. RESULTS: During the follow-up period of 2.26 +/- 0.66 years, 9 patients died (5 in the TT, 2 in the CT and 2 in the CC genotype group; P = 0.34) and 22 returned to dialysis treatment (7 in the TT, 9 in the CT and 6 in the CC genotype group; P = 0.65). There was also no influence of MTHFR 1298A-->C genotypes (AA genotype, 114 patients; AC genotype, 64 patients; CC genotype, 11 patients) on patient or graft survival (P = 0.7087 and P = 0.1633, respectively). Two of 93 patients with a tHcy plasma level < or = 15 micromol/L died, in contrast to 7 of 96 patients in the tHcy > 15 micromol/L group, P = 0.0778. Two patients in the low tHcy group had to return to dialysis, in contrast to 20 patients in the high tHcy group (P = 0.0001). In the multivariate model there was no significant predictor of patient survival, and the serum creatinine was the only predictor of graft survival (P < 0.0001). CONCLUSIONS: In summary, our study shows that neither MTHFR 677C-->T/1298A-->C genotypes nor hyperhomocysteinemia are independently associated with patient or graft survival following kidney transplantation.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2001

Is there a role of cyclosporine A on total homocysteine export from human renal proximal tubular epithelial cells?

BACKGROUND: Immunosuppressive therapy may influence homocysteine metabolism in allograft recipients. We examined whether cyclosporine A influences the in vitro formation of homocysteine as determined by the measurement of total homocysteine (tHcy) concentrations in supernatants of human renal proximal tubule epithelial cells (hRPTEC), an important site of homocysteine metabolism. METHODS: Cells were incubated with and without vitamins in the presence of low or high methionine concentrations at different cyclosporine A concentrations for 24, 48 and 72 hours (N = 7 for each experiment). The concentration of tHcy in culture supernatants was measured by a fluorescence polarization immunoassay. Data were analyzed by four-way ANOVA, three-way ANOVA and t tests. RESULTS: The Hcy export from hRPTEC (tHcy in the culture supernatant) was 2.69 micromol/L during standard cell culture conditions at time point 24 hours and increased by 28.3% at 48 hours and by 44.6% at 72 hours. Comparisons of tHcy levels in culture supernatants over time by four way ANOVA showed that cyclosporine A at 200 or 800 ng/mL had no influence on tHcy export from hRPTEC (P = 0.67991). In contrast, the presence of vitamins in the medium (P = 0.000001), in vitro methionine loading (P < 0.000001), and prolonged incubation time (P < 0.000001) were associated with an increase of tHcy export from hRPTEC. Significant interactions in this analysis were "vitamins x methionine" (P = 0.001804), "vitamins x time" (P = 0.001478), "methionine x time" (P < 0.000001), and "vitamins x methionine x time" (P = 0.018128), pointing to a combined effect of vitamins in the presence of high methionine concentrations at the later time points. CONCLUSION: Our study shows that hRPTEC export Hcy into the cell culture medium, an effect that is enhanced by in vitro methionine loading and modulated by the presence of vitamins. Cyclosporine A had no major influence on Hcy export from tubule cells. Therefore, our findings do not support the assumption that cyclosporine A elevates total homocysteine plasma levels in organ transplant patients.

Biological Transport, Active↗
PubMed2001

Expanding our interventional skills: placement of totally implantable injection ports by internists/intensivists.

Totally implantable injection ports are usually placed by surgeons or radiologists using fluoroscopic guidance. In a prospective study we evaluated the efficacy of percutaneous insertion of these devices without the use of fluoroscopic control by internists/intensivists experienced in the placement of permanent cuffed catheters. The supraclavicular approach to the subclavian vein was chosen for first line puncture site because of its low rate of malpositions and complications. 101 ports were inserted in 101 consecutive patients, 96 from the supraclavicular approach. Difficulties in introducing the catheter through the peel-away sheath, misplacement into adjacent vessels, secondary migration, or fragmentation of a line were not observed. Function was excellent in all ports. Three pneumothoraces (3%) and three arterial punctures (3%), none of which required intervention, were recorded. Two ports (2%) had to be revised, one due to local hematoma and another because of inadequate catheter length. Catheter survival was 94% in a 30-month observation period. Placement of totally implantable port systems by internists/intensivists experienced in placing central venous lines is safe and efficient, thus the implantation can easily be performed with minimal technical expenditure in the setting of an intensive care unit. The supraclavicular approach is suitable for insertion of permanent infusion port systems without fluoroscopic control.

Adult↗
PubMed2001

Molecular and clinical characterisation of homocystinuria in two Austrian families with cystathionine beta-synthase deficiency.

The influence of the genotype on the phenotypic expression of homocystinuria due to cystathionine beta-synthase (CBS) deficiency is frequently unclear. We therefore investigated the genotype and the phenotype of CBS deficiency in two Austrian families also considering genetic polymorphisms with a putative association with vascular disease (MTHFR 677C-->T, MTHFR 1298A-->C, F5 1691G-->A, F2 20210G-->A) and response to therapy. We identified the CBS 833T-->C/1058C-->T and CBS 828ins104/1358del134 compound heterozygous genotype in our index patients. Both patients showed mental retardation and ectopia lentis. CBS 833T-->C/1058C-->T was associated with severe vascular complications, which was not the case for CBS 828ins104/1358del134. The patient with CBS 828ins104/1358del134 was negative for F5 1691G-->A, F2 20210G-->A, MTHFR 677C-->T, and MTHFR 1298A-->C, while the patient with CBS 833T-->C/1058C-->T was heterozygous for MTHFR 1298A-->C. A combination therapy including pyridoxine, folic acid, hydroxycobalamin, and betaine failed to lower total homocysteine plasma levels below 50 mumol/L in both patients. In summary, our study demonstrates that the CBS 833C/1058T-MTHFR 1298AC genotype can be related to severe vascular disease, while the CBS 828ins104/1358del134-MTHFR 1298AA genotype presents with a somewhat milder clinical phenotype. Both genotypes do not allow for normalisation of total homocysteine plasma levels following vitamin therapy.

Adult↗