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Biomedical subjects

M C Eddy

Publications and source records attributed to M C Eddy.

10 recordsLinked to original sources
PubMed2001

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.

Calcitriol↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Adult↗
PubMed1999

X-linked recessive spondyloepiphyseal dysplasia tarda. Clinical and radiographic evolution in a 6-generation kindred and review of the literature.

We characterize the clinical and radiographic evolution of X-linked recessive spondyloepiphyseal dysplasia tarda (SEDT) in a 6-generation kindred from Arkansas (SEDT(AK)). Our observations show the natural progression of SEDT(AK) and enable carrier detection by radiographic study. We find that, SEDT(AK) manifests as a postnatal defect. Affected hemizygous males can have radiographically normal vertebrae at birth. The pathogenesis seems to involve a developmental disturbance in endochondral bone formation that is reflected most dramatically in vertebrae by a radiographically inapparent ring apophysis. This defect leads to distinctive malformation of the anterior margins of the lumbar vertebrae during childhood. Subsequently, there is degeneration of intervertebral discs and destruction of spinal facet joints. In the femur, the head, neck, and distal condyles are abnormally shaped and become distorted so that osteoarthritis of the hip is not uncommon. Obligate carrier females heterozygous for the SEDT(AK) gene defect demonstrate several similar but more subtle skeletal abnormalities beginning in early adult life. These women seem to be troubled frequently by arthralgia by middle age. The cumulative findings in SEDT(AK) implicate a defect in a gene at Xp22.2-22.1 that engenders a relatively mild disturbance in endochondral bone formation, especially in the axial skeleton. Accounts of large, well-characterized SEDT kindreds remain essential to appreciate fully any interfamily variability of disease expression and to understand better the pathogenesis of the SEDT defect on the X chromosome.

Adult↗
PubMed1999

Polycystic bone disease: A new, autosomal dominant disorder.

We describe a new heritable bone disease characterized radiographically by increasingly numerous and enlarging cyst-like lesions throughout the skeleton. Beginning in early childhood, a father, son, and daughter all suffered from progressively frequent pathological fractures involving such radiolucencies. Healing occurred uneventfully and with little residual pain or deformity. Biochemical parameters of mineral homeostasis and skeletal turnover were normal. Bone scanning showed increased radioisotope uptake primarily in fractures and in the largest collections of the lesions. The histopathology is uncertain, but may reflect a form of intraosseous lipomatosis. This unique condition, which we have provisionally named polycystic bone disease, is inherited as an autosomal dominant trait with a high degree of penetrance.

Bone Cysts↗
PubMed1998

Bilateral radial ray hypoplasia with multiple epiphyseal dysplasia.

We describe a 5-4/12-year-old girl with the unique combination of bilateral radial ray hypoplasia and multiple epiphyseal dysplasia (MED). Radial ray hypoplasia was diagnosed at birth. MED was documented at age 4-3/12 years when she presented with leg pain and short stature and was found to have femoral anteversion and tibial torsion giving rise to severe genu valgum deformity and intoeing. She has no facial anomalies and is developmentally normal. Family history is unremarkable and chromosomal analysis was normal. Investigation of mineral metabolism showed idiopathic hypercalciuria. Surgical lengthening of her severely hypoplastic left radius at age 19 months was successful. Bilateral femoral and tibial osteotomies at age 5-4/12 years corrected her lower limb deformities. This combination of two distinctive but rare skeletal abnormalities may represent a new syndrome.

Abnormalities, Multiple↗
PubMed1997

Metachondromatosis: report of a family with facial features mildly resembling trichorhinophalangeal syndromePediatr Radiol 1997 Nov;27(11):864.

Four members of a family - three of whom have facial features mildly resembling those of the trichorhinophalangeal syndrome, type I, and all of whom manifested appendicular bony prominences similar to trichorhinophalangeal syndrome, type II - were found to have the radiographic findings of metachondromatosis. The radiographic manifestations and evolution of metachondromatosis are depicted in this report.

Adult↗
PubMed1997

X-linked hypophosphatemia: normal renal function despite medullary nephrocalcinosis 25 years after transient vitamin D2-induced renal azotemia.

Nephrocalcinosis (NC) detected by ultrasound is a recognized abnormality for some patients with X-linked hypophosphatemia (XLH) who received vitamin D2 and inorganic phosphate therapy, but is commonly observed in XLH patients treated with 1,25-dihydroxyvitamin D3 and inorganic phosphate supplementation. Nevertheless, long-term follow-up of kidney function in XLH patients with NC detected ultrasonographically has not been reported. We investigated two women with XLH, ages 31 (patient 1) and 39 (patient 2) years, each of whom had suffered at least one documented episode of vitamin D2-induced hypercalcemia and renal azotemia during childhood. Patient 2 had also been treated with inorganic phosphate. No medications for XLH had been taken during adulthood. Renal ultrasonography at our institution demonstrated marked bilateral medullary NC in both women. No other explanation was found for their NC that apparently occurred several decades earlier from medical therapy for XLH. Detailed studies (including creatinine clearance, beta2-microglobulin excretion, and fasting urinary osmolality and acidification) revealed no impairment of kidney function in either patient. Our findings indicate that subradiographic medullary NC acquired during medical therapy for XLH may persist for decades, but with no adverse renal sequelae. Definitive (long-term) assessment of kidney function in the XLH population with NC, however, will be necessary to fully understand the risk of current medical treatment for this most common heritable form of rickets.

Adult↗