Intermediate hyperhomocysteinaemia and compound heterozygosity for the common variant c.677C>T and a MTHFR gene mutation.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the regulation of plasma homocysteine levels. MTHFR deficiency, an autosomal recessive disorder, results in homocystinuria and hypomethioninaemia and presents with highly variable symptoms affecting many organs but predominantly the central nervous system. The common polymorphism of the MTHFR gene, c.677C>T, a known risk factor for elevated plasma homocysteine levels, occurs frequently in the caucasian population. In this study we investigated three subjects with moderate hyperhomocysteinaemia (total plasma homocysteine 72 micromol/L in case 1 and 90 micromol/L in case 3, total non-protein-bound homocysteine 144-186 micromol/L in case 2) but different clinical presentation with no symptoms in case 1, muscle weakness at 17 years of age in case 2, and syncopes and cerebral convulsions at 18 years of age in case 3. Each subject was compound heterozygous for the c.677C>T polymorphism and a novel mutation of the MTHFR gene (case 1: c.883G>A [p.D291N]; case 2: c.1552_c.1553delGA [p.E514fsX536]; case 3: c.616C>T [p.P202S]). Moderately decreased fibroblast MTHFR activity was associated with severely reduced affinity for NADPH and increased sensitivity to inhibition by S-adenosylmethionine (AdoMet) in case 2, and with mild FAD responsiveness in case 3. In case 1, fibroblast MTHFR activity was normal but the sensitivity to inhibition by AdoMet was slightly reduced. This study indicates that the sequence alteration c.677C>T combined with severe MTHFR mutations in compound heterozygous state may lead to moderate biochemical and clinical abnormalities exceeding those attributed to the c.677TT genotype and might require in addition to folate substitution further therapy to normalize homocysteine levels.

[Upper-abdominal ultrasonography and ERCP? (author's transl)]. / Oberbauchsonographie und ERCP? Parallele Untersuchungen bei Patienten mit Verdacht auf Erkrankungen des Gallengangssystems oder der Bauchspeicheldrüse.

Endoscopic retrograde cholangiopancreatography (ERCP) as well as upper-abdominal ultrasonography were performed on 134 patients. Organ structure was optimally demonstrated by ultrasonography in 94 patients (70.2%) and partially in 29 (21.6%) Comparing the diagnostic assessment in 62 patients who had undergone 73 tests and had subsequently been operated on (57) or examined post-mortem (5) there was a statistically significant advantage of ERCP in diseases in which the choledochal duct had been involved. The method was successful in 95% of cases of choledocholithiasis (20 cases) compared with 45% by ultrasound and in 85% of cases of gall-bladder carcinoma which also involved the choledochal duct (38% by ultrasound). In clinically manifest carcinoma of the head of the pancreas (9 cases) and cholecystolithiasis (19 cases) ultrasonography provided the correct diagnosis in 89%, while the results for ERCP were 56% and 74%, respectively.