Growth hormone (GH) insensitivity due to primary GH receptor deficiency.

As demonstrated in Table 2, the differential diagnosis of growth hormone insensitivity (GHI) includes a number of discrete disorders that can be broadly classified as primary or secondary forms. We have selected GHRD (Laron syndrome) as the prototypic disorder of GHI, in part because such dramatic and rapid progress has been made in this clinical condition over the last 6 yr. These advances represent the fortunate convergence of: 1) the cloning of the GHR gene and the identification of deletions and mutations of this gene in GHRD; 2) the development of assay methods for measurement of the GHBP, IGF peptides, and binding proteins; 3) the discovery of a larger number of affected individuals than had been previously suspected, including the recognition and description of a large genetically homogeneous population of GHRD patients in Ecuador; and 4) the production of recombinant IGF-I for therapeutic trials in GHRD.

Circulating growth hormone binding proteins.

The 'high-affinity' growth hormone binding protein (GHBP) corresponds to the extracellular domain of the membrane-associated GH receptor. In man, it is produced by proteolytic cleavage of the extracellular portion of the receptor, while in the rat and mouse, it is the product of alternative splicing of GH receptor mRNA. Because of the relationship between the GHBP and the GH receptor, measurement of serum concentrations of GHBP provide an index of GH receptor concentrations and/or affinity.

Deletion mapping of Aland Island eye disease to Xp21 between DXS67 (B24) and Duchenne muscular dystrophy.

Aland Island Eye Disease (AIED) is an X-linked form of ocular hypopigmentation--also known as Forsius-Eriksson, or type 2, ocular albinism--in which affected males demonstrate subnormal visual acuity, protanomalous red-green colorblindness, axial myopia, astigmatism, hypoplasia of the fovea, and hypopigmentation of the fundus. A patient has previously been described who, in addition to AIED, manifested a contiguous gene syndrome which included congenital adrenal hypoplasia (AHC), glycerol kinase deficiency (GKD), and Duchenne muscular dystrophy (DMD). In the present paper report we report the molecular genetic analysis of his deletion.

Transient myeloproliferative disorder of the Down type in the normal newborn.

Two infants with congenital nonlymphoblastic leukemia were discovered to have mosaicism for trisomy 21. Both infants achieved durable spontaneous remissions. Trisomy was apparently restricted to the leukemic clone and could be detected in neither phytohemagglutinin-stimulated peripheral blood cells or bone marrow in either patient nor in myeloid progenitor cells from the second patient after resolution of the transient myeloproliferative disorder.

Aland Island eye disease (Forsius-Eriksson ocular albinism) and an Xp21 deletion in a patient with Duchenne muscular dystrophy, glycerol kinase deficiency, and congenital adrenal hypoplasia.

Glycerol kinase deficiency (GKD) has been described in isolation and in complex phenotypes including either congenital adrenal hypoplasia, Duchenne muscular dystrophy, or both. Cytogenetic and molecular studies have localized these defects to a deletion involving the X chromosome at band Xp21, consistent with its X-linked recessive pattern of inheritance. Other clinical findings in the complex glycerol kinase deficiency (CGKD) patients are mental retardation, short stature, and hypogonadotropic hypogonadism.

Late presenting, prolonged hypocalcemia in an infant of a woman with hypocalciuric hypercalcemia.

Familial hypocalciuric hypercalcemia (FHH) is a benign autosomal dominant disorder. Infants affected with FHH however, born to unaffected mothers may develop life-threatening autonomous hyperparathyroidism, the mechanism of which is not clearly understood. There is little information recorded in the literature regarding the opposite scenario, i.

Necrotizing otitis externa during induction therapy for acute lymphoblastic leukemia.

In three children who were receiving acute lymphoblastic leukemia induction therapy and were severely neutropenic, necrotizing otitis externa developed. Two patients had a probing maneuver to their ear canal. Pseudomonas aeruginosa was isolated in heavy growth from the external canal of three patients and other tissues of one patient.

Massive levothyroxine ingestion. Conservative management.

The clinical course of a 29-month-old girl who was referred for evaluation after ingesting ninety 0.2-mg tablets of levothyroxine is reported. Despite an initial thyroxine (T4) level of 282 micrograms/dl and a triiodothyronine (T3) level of 1,837 ng/dl at 48 hours postingestion, her symptoms were mild and included irritability, vomiting, tremor, and tachycardia.

Prolonged defects of interleukin-2 production, responsiveness, and receptor expression in patients with acute lymphoblastic leukemia.

The proliferative responsiveness to, production of, and the expression of cell-surface receptors for interleukin-2 (IL-2) were examined in 14 children with acute lymphoblastic leukemia (ALL) in remission and receiving maintenance chemotherapy for 6 to 35 months; in 19 children with ALL in remission and off all therapy for 2 to 138 months; and 15 control subjects. Short-term concanavalin A (Con A)-activated, purified T lymphocytes from patients on, as well as patients off, therapy had a significantly decreased proliferative responsiveness to a saturating amount of exogenous, recombinant IL-2 as compared to control subjects (P less than 0.005 and less than 0.

Attenuation of asparaginase-induced hyperglycemia after substitution of the Erwinia carotovora for the Escherichia coli enzyme preparation.

L-asparaginase, an enzyme with established antileukemic activity, increases the induction rate and duration of remission of acute lymphoblastic leukemia when added to vincristine and prednisone for induction therapy. Enzymes derived from two different bacterial sources (Escherichia coli and Erwinia carotovora) are in common use. These enzymes may be associated with toxic reactions of differing frequency and severity.

Interleukin 2 production, proliferative response, and receptor expression by cord blood mononuclear cells.

To analyze the elements of the interleukin 2 (IL-2) system in newborns, the proliferative responsiveness to, production of, and expression of cell surface receptors for IL-2 were quantitated in cord blood mononuclear cells (CBMC) from 25 normal, full-term newborns and were compared to results in peripheral blood mononuclear cells (PBMC) from 15 juveniles and 28 adults in order to examine the IL-2 system as a function of age. Proliferative responsiveness of purified cord blood T lymphocytes to a saturating amount of human, recombinant IL-2 was significantly greater (p less than 0.05) than that of T lymphocytes from juveniles or adults at all three cell concentrations used.