Pseudo-(tumor-induced) rickets.

An athletic 8-year-old boy developed severe muscle weakness over 2 years. At the age of 10 years, investigation for possible neuromuscular disease disclosed hypophosphatemia (1.8 mg/dl) and rickets. There was selective renal tubular wasting of inorganic phosphate (Pi) but no history of toxin exposure, familial bone or kidney disease, or biochemical evidence of vitamin D deficiency. Urine amino acid quantitation was unremarkable. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] concentration was in the lower half of the reference range. Our presumptive diagnosis was tumor-induced rickets; however, physical examination and bone scanning in search of a neoplasm were unrevealing. Soon after 1,25(OH)2D3 and Pi treatment began, muscle strength improved considerably. After 6 months of therapy, radiographic abnormalities were substantially better. During the next 6 years, physical examinations, a second bone scan, whole-body and nasal sinus magnetic resonance imaging, and octreotide scintigraphy were unremarkable. When his physes fused at the age of 16 years, assessment of his course showed excellent control of his rickets requiring decreasing doses of medication. Furthermore, fasting serum Pi levels and tubular maximum phosphorus/glomerular filtration (TmP/ GFR) values had increased steadily and normalized after 3 years of treatment. Accordingly, therapy was stopped. Seven months after stopping medication, he continues to feel completely well. Fasting serum Pi levels, TmP/GFR, other biochemical parameters of bone and mineral homeostasis, creatinine clearance, and renal sonography are normal. Neither spontaneous or pharmacologic cure of tumor-induced rickets or osteomalacia nor a patient matching ours has been reported. His disorder, which we call pseudo-(tumor-induced) rickets, should be considered when investigation for oncogenic rickets or osteomalacia discloses no causal lesion. Consequently, prolonged medical therapy and futile searches for a neoplasm may be avoided.

Retinal and intraventricular cerebral hemorrhages in the preterm infant born at or before 30 weeks' gestation.

PURPOSE: To determine the prevalence of retinal hemorrhages and their association with cerebral intraventricular hemorrhages (IVH) in low-birth-weight preterm neonates born at or before 32 weeks' gestation. METHODS: We prospectively studied a consecutive series of 22 neonates (24-30 weeks' gestation; mean gestational age, 27 weeks; mean weight, 1065 g) admitted to the neonatal intensive care unit. Anterior segment and indirect ophthalmoscopic examination, as well as cranial ultrasonographic examination, were performed on day 1 and day 10 of life. The prevalence of retinal and intraventricular hemorrhage was tested statistically for association with obstetric and neonatal clinical variables. RESULTS: The prevalence of retinal hemorrhage was 9% (2/22; 95% CI, 3%-21%) on day 1 and 2% (1/22) on day 10. The prevalence of IVH was 27% (6/22; 95% CI, 9%-46%): 14% (3/22) on day 1 and 23% (5/22) on day 10. Retinal hemorrhages occurred with greater frequency in neonates born to women who had intrauterine infection (chorioamnionitis, P =.043) and low umbilical cord pH levels (P =.027). No association was found between the presence of retinal hemorrhage and IVH (P = 1.000), mode of delivery (ie, vaginal vs cesarean section, P = 1.000), birth weight (P =.476), or gestational age (P = 1.000). The presence of subconjunctival hemorrhage was associated with IVH (P =.046). CONCLUSIONS: Retinal hemorrhages occur in less than 10% of low-birth-weight neonates, ie, a prevalence one half that observed in term neonates (22%). The hemorrhages tend to resolve without sequelae in the first 10 days of life and occur more commonly in infants born to women with uterine infection. Retinal hemorrhages in very premature neonates are not predictive of IVH-related brain damage.

Vision readiness of the reserve forces of the U.S. Army.

In 1996 and 1997, the Army conducted an exercise to assess the ability to rapidly mobilize the reserve forces. In accordance with Army requirements, each soldier was evaluated to determine if he or she met vision and optical readiness standards. Of the 1,947 individuals processed through the optometry section, 40% met vision requirements without correction and 32% met vision requirements with their current spectacles. The remaining 28% required examination. A major impediment to processing reserve units for deployment is the lack of vision and optical readiness. In the mobilization for the Persian Gulf War, significant delays were incurred because of the time required to perform eye examinations and fabricate eyewear. However, as a result of this exercise, current prescriptions will be available in the event of mobilization. To ensure readiness, all units should perform such exercises periodically.

Preonset studies of spondyloepiphyseal dysplasia tarda caused by a novel 2-base pair deletion in SEDL encoding sedlin.

Spondyloepiphyseal dysplasia tarda (SEDT), an X-linked recessive skeletal disorder, presents with disproportionate short stature and "barrel-chest" deformity in affected (hemizygous) adolescent boys. In four reported families to date, mutations in a gene designated SEDL (spondyloepiphyseal dysplasia late) cosegregate with SEDT. We diagnosed SEDT in a short-stature, kyphotic 15-year-old boy because of his characteristic vertebral malformations. Clinical manifestations of SEDT were evident in at least four previous generations. A novel 2-base pair (bp) deletion in exon 5 of SEDL was found in the propositus by polymerase chain reaction (PCR) amplification and sequencing of all four coding exons. The mutation ATdel241-242 cosegregated with the kindred's skeletal disease. The deletion is adjacent to a noncanonical splice site for exon 5 but does not alter splicing. Instead, it deletes 2 bp from the coding sequence, causing a frameshift. A maternal aunt and her three young sons were investigated subsequently. Radiographs showed subtle shaping abnormalities of her pelvis and knees, suggesting heterozygosity. X-rays of the spine and pelvis of her 8-year-old son revealed characteristic changes of SEDT, but her younger sons (aged 6 years and 3 years) showed no abnormalities. SEDL analysis confirmed that she and only her eldest boy had the 2-bp deletion. Molecular testing of SEDL enables carrier detection and definitive diagnosis before clinical or radiographic expression of SEDT. Although there is no specific treatment for SEDT, preexpression molecular testing of SEDL could be helpful if avoiding physical activities potentially injurious to the spine and the joints proves beneficial.

Expansile skeletal hyperphosphatasia: a new familial metabolic bone disease.

We describe a new familial metabolic bone disease characterized by expanding hyperostotic long bones, early onset deafness, premature tooth loss, and episodic hypercalcemia. The condition affects a mother and daughter studied at the age of 36 years and 11 years, respectively. Both individuals lost all hearing in early childhood and suffered premature shedding of teeth. Skeletal pains began just before puberty. Swelling and aching of most middle phalanges in the hands is an especially troublesome manifestation. The mother also had episodes of symptomatic hypercalcemia first documented in late childhood and subsequently during intercurrent illness and postpartum lactation. Radiographs show hyperostosis and/or osteosclerosis predominantly in the skull and appendicular skeleton. Long bones also are expanded considerably, especially the middle phalanges in the fingers. The mother's skeletal abnormalities are more severe. Biochemical parameters of bone turnover, including serum alkaline phosphatase (ALP) activity, are elevated substantially. In the proposita, dynamic histomorphometry of nondecalcified sections of iliac crest revealed rapid skeletal remodeling. In the mother, who had been treated with bisphosphonates, electron microscopy (EM) showed disorganized collagen bundles as well as necrotic and apoptotic bone cells but no osteocytic osteolysis. Measles virus gene transcripts were not detected in peripheral blood monocytes. Karyotyping was normal, 46,XX. Hyperphosphatasia with bone disease previously has been reported as either a sporadic or autosomal recessive condition. Expansile skeletal hyperphosphatasia (ESH) is probably inherited as an autosomal dominant trait with a high degree of penetrance.

Deficiency of the alpha-subunit of the stimulatory G protein and severe extraskeletal ossification.

Progressive osseous heteroplasia (POH) is a rare disorder characterized by dermal ossification beginning in infancy followed by increasing and extensive bone formation in deep muscle and fascia. We describe two unrelated girls with typical clinical, radiographic, and histological features of POH who also have findings of another uncommon heritable disorder, Albright hereditary osteodystrophy (AHO). One patient has mild brachydactyly but no endocrinopathy, whereas the other manifests brachydactyly, obesity, and target tissue resistance to thyrotropin and parathyroid hormone (PTH). Levels of the alpha-subunit of the G protein (Gsalpha) were reduced in erythrocyte membranes from both girls and a nonsense mutation (Q12X) in exon 1 of the GNAS1 gene was identified in genomic DNA from the mildly affected patient. Features of POH and AHO in two individuals suggest that these conditions share a similar molecular basis and pathogenesis and that isolated severe extraskeletal ossification may be another manifestation of Gsalpha deficiency.

Vertebral anomalies in a new family with ODED syndrome.

We report a new family with oculodigitoesophagoduodenal syndrome (ODED syndrome), which associates microcephaly, abnormalities of the hands and feet, shortened palpebral fissures, tracheoesophageal fistula and duodenal atresia. In addition, previously unreported vertebral anomalies are described. This report further delineates the clinical and radiographic spectrum of this syndrome, providing useful information for diagnosis and family counseling.