Impact of HLA matching on outcome of hematopoietic stem cell transplantation in children with inherited diseases: a single-center comparative analysis of genoidentical, haploidentical or unrelated donors.

SUMMARY: Hematological inherited diseases can be cured by hematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical sibling donor (MSD), but the outcome of unrelated donors (URD) or haploidentical donors (HMD) has been a cause of concern. In all, 94 children affected with inherited diseases underwent HSCT at a single center using MSD (group A, n=31), URD (group B, n=23) or HMD (group C, n=40). There was no difference in the rate of engraftment or in the incidence of grades III-IV acute graft-versus-host disease (GVHD) between the groups. Survival rate was 80.6% in group A, 62.5% in group B and 47.5% in group C (P=0.023). In group B, survival rate was 73.7% in the subgroup with zero or one class I mismatch, and 25% in the subgroup with two or more class I mismatches (P=0.04). In group C, survival rate was 83.3% in the 9/10-identical subgroup, 64.3% in the seven or 8/10 subgroup, and 25% in the five or 6/10 subgroup (P=0.0007). Thus, engraftment, incidence of GVHD and survival are similar in recipients of grafts from MSD, URD with 0-1 class I-mismatch, or HMD with at least 7/10 HLA matches. The low success of HSCT using more disparate donors suggests reserving them for patients with very poor prognosis.

Osteomalacia secondary to celiac disease, primary hyperparathyroidism, and Graves' disease.

Primary hyperparathyroidism is seldom associated with other autoimmune disorders. The presence of normocalcemia in primary hyperparathyroidism should prompt the physician to look for vitamin D deficiency. This observation concerns a 34-year-old vegetarian woman with combined primary hyperparathyroidism, Graves' disease, and celiac disease. The patient presented with severe bone deformities; she was unable to walk, and had severe muscular weakness and weight loss. Biochemical findings revealed severe hyperparathyroidism with normocalcemia, hypophosphatemia, very low urinary calcium, and low 25-hydroxy vitamin D level. Thyroid tests showed hyperthyroidism with positive thyroid receptor antibodies, confirming the presence of Graves' disease. Positive antigliadin and antireticulin antibodies and complete villous atrophy on duodenal biopsy established the presence of celiac disease. The patient underwent a near-total thyroidectomy, with the removal of a parathyroid adenoma. To our knowledge, this observation is the first finding of an association between celiac disease, Graves' disease, and primary hyperparathyroidism. It emphasizes the need to rule out intestinal malabsorption in the case of normocalcemic hyperparathyroidism.

[Significance of TSH receptor antibody determination]. / Intérêt du dosage des anticorps antirécepteurs à la TSH.

TSH receptor antibodies (TRAb) was performed by binding assay in seventy-seven patients (47 with Graves disease, 32 with other thyroid abnormalities). The sensitivity and specificity of our assay were respectively 81% and 96.5%. These results were similar to the results found in medical literature. The association of ophthalmopathy with Graves disease does not increase the sensitivity of the test. In this study we conclude that TRAb assay is of great interest in confirming the diagnosis and in the following of Graves disease.

[Thyroid-stimulating hormone hypophyseal adenoma. A case report]. / Adénome hypophysaire à TSH. A propos d'un cas.

TSH pituitary adenomas represent less than 1% of operated pituitary adenomas. More then 200 cases have been described till now and more patients are now identified since the widespread of ultrasensitive TSH assay which can detect paradoxical situations of elevated serum thyroxine levels with detectable TSH levels. Differential diagnosis must be done with pituitary resistance to thyroid hormones, disorder in which there is a state of "TSH mediated hyperthyroidism". Transsphenoidal surgery remains the treatment of choice of TSH secreting adenoma. A medical treatment with octreotide can improve biological findings and induce tumor shrinking. We report in this paper a TSH pituitary adenoma in a young girl of 15 years old.

[Importance of peptide C determination in diabetes]. / Intérêt du dosage du peptide C dans le diabète.

The peptide C, polypeptide secreted by the pancreas at the same time as insulin, presents a great interest in the evaluation of diabetic patients. First it allows a differentiation between insulin dependent diabetes (IDD) and non insulin dependent (NDD). A low and non stimulated levels of peptide C signifies an insulin dependence. Within the group of IDD patients the peptide C was low when the diabetes was discovered at a younger age and its secretion diminished as the diabetes progresses. The peptide C has also a prognostic interest in IDD. Low and non stimulable levels of peptide C signifies a difficult control of diabetes which needs two injections per day while high and stimulable levels will be seen in diabetes easy to control with one injection of insulin. Finally, values of peptide C does not permit to predict the onset of diabetic complications (retinopathy, acidocetosis) as well as the control of patients.

[Primary hyperparathyroidism. Experiences at the Hôtel Dieu. A study of 28 cases]. / Hyperparathyroïdie primaire. Expérience de l'Hôtel-Dieu. Etude de 28 cas.

Primary hyperparathyroidism is a more frequently recognized entity. The clinical picture historically severe, has changed overtime. We present herein our experience relating 28 cases with emphasis of our results compared to the medical literature.

Sequence of a human brain adenylyl cyclase partial cDNA: evidence for a consensus cyclase specific domain.

A cDNA coding for a human brain adenylyl cyclase was isolated and sequenced. The deduced partial 675 amino-acid sequence was compared with those of other known adenylyl and guanylyl cyclases. Comparison of this predicted amino-acid sequence with that of bovine brain (type I) and rat olfactory (type III) adenylyl cyclase indicated a significant homology with the carboxyl-terminal halves of both enzymes. The homology between the human adenylyl cyclase and the other two mammalian adenylyl cyclase also appears at the topographic level. Indeed, the human enzyme includes a extremely hydrophobic region containing six potential membrane-spanning segments followed by a large hydrophilic domain. At the beginning of the hydrophilic domain, there is a 250 amino-acid region which shows not only a striking homology with the bovine and rat adenylyl cyclase (86% of similarity and 57% of identity), but also a significant homology with non-mammalian adenylyl cyclase and guanylyl cyclases. We found that this 250 amino-acid domain contains a sequence of about 165 amino-acids which is highly conserved in most of the known nucleotide cyclases suggesting that it includes residues that are critical for the function of the enzymes.

Different chromosomal localization of two adenylyl cyclase genes expressed in human brain.

Recently, we characterized a cDNA clone that encodes a human brain adenylyl cyclase (HBAC1). In the present study, we identified a second population of mRNA suspected to encode a new brain adenylyl cyclase (HBA C2). The amino acid sequence of HBA C2 displays significant homology with HBA C1 in the highly conserved adenylyl cyclase domain (250 aminio acids), found in the 3' cytoplasmic domain of all mammalian adenylyl cyclases. However, outside this domain, the homology is extremely low, suggesting that the corresponding mRNA originates from a different gene. We report here the first chromosomal localization of the adenylyl cyclase genes determined by in situ hybridization of human metaphase chromosomal spreads using human brain cDNA probes specific for each mRNA. The probe corresponding to HBA C1 exhibited a strong specific signal on chromosome 8q24, with a major peak in the band q24.2. In contrast, the HBA C2 probe hybridized to chromosome 5p15, with a major peak in the band p15.3. The two cDNAs hybridized at the two loci without any cross reactivity. Thus, in human brain, a heterogeneous population of adenylyl cyclase mRNAs is expressed, and the corresponding genes might be under the control of independent regulatory mechanisms.