Which parameters predict correction of the intermetatarsal angle after first metatarsophalangeal fusion?

Fusion of the first metatarsophalangeal joint (MTPJ) is a commonly performed surgical procedure. Although the effect of first MTPJ fusion on reduction of Intermetatarsal angle (IMA) is well described, contributing factors remain unclear. The aim of this study was to identity predictive parameters for IMA reduction. Fifty-one patients (68 feet) who underwent a first MTPJ fusion and had an IMA greater than fourteen degrees were assessed retrospectively. The average age was 68 (31.4-79.3) years. Sixteen demographic and radiographic variables were evaluated using a multivariate regression analysis for association with change in IMA after surgery. The mean preoperative IMA was 16.11 (range, 14.0-22.5) degrees with a mean reduction of 4.95 (range, 0-17) degrees after surgery. Multivariate regression analysis revealed three significant independent predictors of the change in IMA. Increased preoperative IMA (ß = .663, CI = .419, .908, P <.001), increased preoperative translation at base of MT1 (ß = .490, CI = 0.005, .974, P = 0.039), and less postoperative translation in the fusion (ß= -0.693, CI= -1.054, -.331, P= 0.002) significantly increased the amount of IMA reduction. Pre-operative IMA and translation at the base of the first metatarsal were positive predictors for correction of IMA after first MTPJ fusion. Translation at the level of the MTP I fusion was a negative predictor for the amount of IMA correction. Based on these findings, we recommend minimizing the lateral translation of the proximal phalanx relative to the metatarsal head to optimize IMA correction after MTPJ fusion.

RFT1-CDG: deafness as a novel feature of congenital disorders of glycosylation.

Congenital disorders of glycosylation (CDG) are genetic diseases due to defects in the synthesis of glycans and in the attachment of glycans to lipids and proteins. Actually, some 42 CDG are known including defects in protein N-glycosylation, in protein O-glycosylation, in lipid glycosylation, and in multiple and other glycosylation pathways. Most CDG are multisystem diseases and a large number of signs and symptoms have already been reported in CDG. An exception to this is deafness. This symptom has not been observed as a consistent feature in CDG. In 2008, a novel defect was identified in protein N-glycosylation, namely in RFT1. This is a defect in the assembly of N-glycans. RFT1 is involved in the transfer of Man(5)GlcNAc(2)-PP-Dol from the cytoplasmic to the luminal side of the endoplasmic reticulum. According to the novel nomenclature (non-italicized gene symbol followed by -CDG) this defect is named RFT1-CDG. Recently, three other patients with RFT1-CDG have been reported and here we report two novel patients. Remarkably, all six patients with RFT1-CDG show sensorineural deafness as part of a severe neurological syndrome. We conclude that RFT1-CDG is the first 'deafness-CDG'. CDG should be included in the work-up of congenital, particularly syndromic, hearing loss.

The normal phenotype of Pmm1-deficient mice suggests that Pmm1 is not essential for normal mouse development.

Phosphomannomutases (PMMs) are crucial for the glycosylation of glycoproteins. In humans, two highly conserved PMMs exist: PMM1 and PMM2. In vitro both enzymes are able to convert mannose-6-phosphate (mannose-6-P) into mannose-1-P, the key starting compound for glycan biosynthesis. However, only mutations causing a deficiency in PMM2 cause hypoglycosylation, leading to the most frequent type of the congenital disorders of glycosylation (CDG): CDG-Ia. PMM1 is as yet not associated with any disease, and its physiological role has remained unclear. We generated a mouse deficient in Pmm1 activity and documented the expression pattern of murine Pmm1 to unravel its biological role. The expression pattern suggested an involvement of Pmm1 in (neural) development and endocrine regulation. Surprisingly, Pmm1 knockout mice were viable, developed normally, and did not reveal any obvious phenotypic alteration up to adulthood. The macroscopic and microscopic anatomy of all major organs, as well as animal behavior, appeared to be normal. Likewise, lectin histochemistry did not demonstrate an altered glycosylation pattern in tissues. It is especially striking that Pmm1, despite an almost complete overlap of its expression with Pmm2, e.g., in the developing brain, is apparently unable to compensate for deficient Pmm2 activity in CDG-Ia patients. Together, these data point to a (developmental) function independent of mannose-1-P synthesis, whereby the normal knockout phenotype, despite the stringent conservation in phylogeny, could be explained by a critical function under as-yet-unidentified challenge conditions.