William Reed

The Winchester syndrome: a nonlysosomal connective tissue disease.

The Winchester syndrome, a recently recognized inherited disorder of connective tissue, consists of dwarfism, contractures, skin lesions, corneal opacities, osteoporosis, carpal-tarsal osteolysis, and rheumatoid-like small joint destruction. We have studied the third, fourth, and fifth recognized cases of this disorder and find: (1) progressive lysis of carpal and tarsal bones; (2) replacement of bone and cartilage by dense fibrous tissue containing abnormal blood vessels; (3) scanty trabecular and cortical bone, but normal resting cartilage and growth plates; (4) hypervascularity apparently associated with osteolysis at large joints; and (5) widespread proliferation of ultrastrurally abnormal fibroblasts. Although this disorder was originally postulated to be a new mucopolysaccharidosis, we find no evidence for a lysosomal storage disease, and propose reclassification of this disorder as a nonlysosomal connective tissue disease.

Collection of sibling donor cord blood for children with thalassemia.

Bone marrow transplantation has curative potential for patients with thalassemia major who have a matched sibling marrow donor, but usefulness of alternative stem cell sources is undergoing investigation. Cord blood (CB) from a sibling has different characteristics from marrow and has potential advantages and disadvantages as a stem cell source. Whereas many families caring for a child with thalassemia major (or other transplant-treatable condition) experience an additional pregnancy, most give birth at hospitals without the infrastructure needed to collect and process the new infants CB. To address this, and with funding from the National Institutes of Health, we have developed the first noncommercial CB program, operating across the United States, designed specifically to facilitate medically indicated CB collections from sibling donors. Using a case-management model, we have collected CB for 25 thalassemia families in eight states. Three of these CB units have now been used for transplantation; two others are human leukocyte antigen-identical and contain adequate nucleated cell dose to perform transplantation in their intended recipient. We conclude that a CB bank focused on sibling donations may be a useful stem cell resource and that families with specific medical need, such as a child with thalassemia, should consider preserving CB from siblings.

Sickle-cell disease not identified by newborn screening because of prior transfusion

Erythrocyte transfusion can impair detection of sickle-cell disease, galactosemia, or biotinidase deficiency with newborn screening. We report on 4 infants with SCD in whom delayed diagnosis was associated with neonatal transfusion. In 2 cases, the initial newborn screening showed no hemoglobin S. In no case was the recommended screening >/=120 days from the last transfusion obtained. Two children had significant SCD-related morbidity before diagnosis.

The Skin in the Winchester Syndrome: Histologic and Ultrastructural Studies

The Winchester syndrome, a rare inherited disorder, is characterized by dwarfism, carpal-tarsal osteolysis, rheumatoidlike small joint destruction, corneal opacities, and thickening and hypertrichosis of the skin, unlike that seen in other genodermatoses. The early stages of cutaneous abnormalities are characterized by proliferation of fibroblasts deep in the dermis, while hypocellular homogenization of the collagen is evident later. Ultrastructural peculiarities of fibroblasts include dilated and vacuolated mitochondria, the presence of varying amounts of myofilaments in the cytoplasm, and a prominent fibrous nuclear lamina. Cells other than fibroblasts display no abnormalities. The basic defect in this disorder is unknown; however, it may be related to abnormal function of fibroblasts.

Sibling donor cord blood banking for children with sickle cell disease.

Although hematopoietic stem cell transplantation has curative potential for selected patients with sickle cell disease (SCD), most patients who are eligible for transplantation do not have a suitable donor. Cord blood (CB) from a sibling could provide an alternative stem cell source that, while not as well established as marrow, may offer certain advantages for selected families. These potential advantages include low risk to the infant donor, the possibility that mismatched CB units from sibling donors may be acceptable for transplantation, prompt availability of a stored CB unit for transplant, and decreased risk of clinically significant graft-versus-host disease. When families with SCD (or other transplant-treatable condition) conceive a sibling, no comprehensive research resource exists to assist the family in collecting the new infants CB. With support from the National Heart Lung and Blood Institute, we are developing a noncommercial research-based CB Banking Program specifically for medically indicated sibling donations. In preliminary experience, we have collected CB from 52 SCD families across 19 states. Of these, 2 CB units have thus far been used for transplantation and 9 others are HLA-identical. We conclude that a CB bank focusing on sibling-donations may be feasible, but further study is required to determine whether such a bank can colled CB units of sufficient quantity and quality to support controlled trials of sibling CB transplantation. Families with a specific medical need, such as those already caring for a child with SCD, should consider collecting sibling CB as part of comprehensive care if the opportunity becomes available.