Citations

Purpose Our purpose was to evaluate the results of transphyseal anterior cruciate ligament (ACL) reconstruction with medial hamstring autograft in skeletally immature patients. Methods We reviewed the records of all skeletally immature patients who underwent transphyseal ACL reconstruction with medial hamstring autograft between 1988 and 2002 at our institution. Inclusion criteria were age less than 15 years for male patients, age less than 14 years for female patients, and radiographic evidence of wide open physes. We identified 16 patients (11 male and 5 female). All underwent preoperative and postoperative clinical evaluation (physical examination and modified Lysholm and International Knee Documentation Committee scores), and knee radiographs. Each patient was followed up until skeletal maturity was confirmed, with a mean clinical follow‐up of 41.1 months (range, 24 to 112 months). Results The mean time from ACL injury to reconstruction was 5.6 months (range, 0.7 to 26.9 months). During the preoperative time period, 4 patients (25%) developed meniscal tears that were not visualized on the index magnetic resonance imaging scans. At last follow‐up, the mean leg length discrepancy measured 0.62 cm (range, 0.2 to 1.5 cm), and clinical or radiographic evidence of malalignment was not present in any of the patients. In 1 patient a symptomatic 1.5‐cm limb overgrowth developed, which was treated with an internal shoe lift. At follow up, the mean modified Lysholm score was 98.8 (range, 94 to 100), and the mean International Knee Documentation Committee score was 89.9 (range, 73.6 to 94.3). Of the patients, 7 (43.8%) underwent a reoperation, and 2 suffered traumatic graft disruption. Conclusions ACL reconstruction with a medial hamstring autograft via a transphyseal technique yields satisfactory clinical results in skeletally immature patients. No new meniscal tears were identified after ACL reconstruction, and most patients (87.5%) returned to their previous level of activity. The rate of reoperation was high (43.8%). Physeal growth arrest did not occur. Level of Evidence Level IV, therapeutic case series.

The multivesicular body (MVB) sorting pathway impacts a variety of cellular functions in eukaryotic cells. Perhaps the best understood role for the MVB pathway is the degradation of transmembrane proteins within the lysosome. Regulation of cargo selection by this pathway is critically important for normal cell physiology, and recent advances in our understanding of this process have highlighted the endosomal sorting complexes required for transport (ESCRTs) as pivotal players in this reaction. To better understand the mechanisms of cargo selection during MVB sorting, we performed a genetic screen to identify novel factors required for cargo-specific selection by this pathway and identified the Mvb12 protein. Loss of Mvb12 function results in differential defects in the selection of MVB cargoes. A variety of analyses indicate that Mvb12 is a stable member of ESCRT-I, a heterologous complex involved in cargo selection by the MVB pathway. Phenotypes displayed upon loss of Mvb12 are distinct from those displayed by the previously described ESCRT-I subunits (vacuolar protein sorting 23, -28, and -37), suggesting a distinct function than these core subunits. These data support a model in which Mvb12 impacts the selection of MVB cargoes by modulating the cargo recognition capabilities of ESCRT-I.

Abstract Congenital erythropoietic porphyria (CEP), an autosomal recessive disorder, is due to mutations of uroporphyrinogen III synthase (UROS). Deficiency of UROS results in excess uroporphyrin I, which causes photosensitization. We evaluated a 3-year-old boy with CEP. A hypochromic, microcytic anemia was present from birth, and platelet counts averaged 70 × 109/L (70 000/μL). Erythrocyte UROS activity was 21% of controls. Red cell morphology and globin chain labeling studies were compatible with β-thalassemia. Hb electrophoresis revealed 36.3% A, 2.4% A2, 59.5% F, and 1.8% of an unidentified peak. No UROS or α- and β-globin mutations were found in the child or the parents. The molecular basis of the phenotype proved to be a mutation of GATA1, an X-linked transcription factor common to globin genes and heme biosynthetic enzymes in erythrocytes. A mutation at codon 216 in the child and on one allele of his mother changed arginine to tryptophan (R216W). This is the first report of a human porphyria due to a mutation in a trans-acting factor and the first association of CEP with thalassemia and thrombocytopenia. The Hb F level of 59.5% suggests a role for GATA-1 in globin switching. A bone marrow allograft corrected both the porphyria and the thalassemia.