ABSTRACT
An 11-year-old black male presenting with severe subacute sensory ataxia, unusual skin hyperpigmentation, megaloblastic anemia, low serum B12 levels, and an abnormal part I Schilling test was diagnosed with pernicious anemia in the context of a polyglandular syndrome. Intrinsic factor and thyroid microsomal antibodies were positive, and thyroid-stimulating hormone levels were undetectable. There was a strong familial aggregation because the mother, a maternal aunt, the maternal grandfather, and the maternal great-grandmother had been diagnosed with pernicious anemia, albeit of unspecified etiology. Spinal magnetic resonance imaging (MRI) demonstrated extensive demyelination of the posterior columns along the entire length of the cord, as well as areas of contrast enhancement. Treatment with cobalamin produced complete remission of the neurologic deficits and normalization of the MRI findings in the short space of 2 months. Although rare, childhood pernicious anemia is a treatable disease that should be included in the differential diagnosis of the sensory ataxias in children. In this article, we review the causes of pernicious anemia in children and discuss the MRI findings.
Subject(s)
Anemia, Pernicious/complications , Gait Ataxia/etiology , Polyendocrinopathies, Autoimmune/diagnosis , Spinal Cord/pathology , Vitamin B 12/therapeutic use , Anemia, Pernicious/drug therapy , Anemia, Pernicious/genetics , Anemia, Pernicious/pathology , Child , Diagnosis, Differential , Gait Ataxia/pathology , Humans , Magnetic Resonance Imaging , Male , Polyendocrinopathies, Autoimmune/complications , Polyendocrinopathies, Autoimmune/pathology , Remission Induction , Schilling Test , Vitamin B 12/bloodABSTRACT
Calbindin-D28k is a highly conserved 28,000 (dalton) molecular-weight (Mr) calcium binding protein with broad tissue distribution, yet cell-type-specific expression predominantly in subpopulations of central and peripheral nervous system neurons, distal tubular cells of the kidney, and enteric neuroendocrine cells. A polyclonal antiserum against rat renal calbindin-D28k and a monoclonal antibody to calbindin-D28k purified from chicken intestine (clone CL-300) were used for immunohistochemical evaluation of formalin-fixed, paraffin-embedded tissues from multiple areas of the human small and large intestines and 93 primary neoplasms of the gastrointestinal tract (foregut, midgut, and hindgut derivatives) and the lung (foregut derivative). Calbindin-D28k immunostaining was obtained in a minority of enterochromaffin (neuroendocrine) cells, predominantly of the appendix and small intestine, as well as in autonomic neurons of the neural plexuses. Focal cytoplasmic Golgi-type staining was obtained with monoclonal antibody CL-300 in the appendiceal surface epithelium and dendritic macrophages confined to the appendiceal lymphoid follicles. Epithelial progenitor cells in enteric crypts and absorptive, goblet, and Paneth cells were calbindin-D28k negative, while no immunoreactivity was demonstrated in the mucosae of the colon and rectum. Calbindin-D28k staining was consistently detected in subpopulations of neuroendocrine phenotypes in midgut (appendiceal/ileal) and foregut (bronchial) carcinoids and small-cell carcinomas, but was absent in adenocarcinomas, squamous cell carcinomas, leiomyomas/leiomyosarcomas, schwannomas, and lymphomas. Our observations suggest that calbindin-D28k is a novel adjuvant neuroendocrine marker that is potentially useful in diagnostic tumor immunohistochemistry.