Phenotypic Evaluation of a Family Cohort with Hemolytic Anemia
Notice bibliographique
Résumé
Abstract Abstract 3214 Background: We have identified a kindred in Manitoba and Saskatchewan, Canada, affected by non-immune hemolytic anemia. Red cell morphology, an elevated MCHC and decreased osmotic fragility are consistent with hereditary xerocytosis, a rare hemolytic disorder, for which the causative genetic mutation is unknown. Objectives: To describe the clinical phenotype and inheritance of an uncharacterized chronic hemolytic disorder in a large kindred. Methods: With assistance from each consenting family member, a pedigree was constructed. A focused history was taken and the presence of splenomegaly was assessed by physical examination. Laboratory analysis included a CBC, reticulocyte count, osmotic fragility and peripheral blood film. Biochemical measurements of LDH, ALT, bilirubin, ferritin, haptoglobin, plasma hemoglobin and methemoglobin were performed. Glycolytic enzymes were evaluated in a subset of patients to rule out other rare causes of hemolysis. Results: The family pedigree captured the genetic relations of 342 individuals spanning 5 generations. Consent to participate in the detailed family study was obtained from 137 family members. The average age of the study population was 29 years (range 8 months to 76 years). Laboratory specimens were collected from 26 unrelated spouses and 111 related individuals. Males represented 48% of the studied population. The distribution of reticulocyte counts was distinctly bimodal with no overlap between the two populations, allowing classification of individuals as phenotypically affected or non-affected. The mean percent reticulocyte count of non-affected subjects (related family members and unrelated spouses) was 1.1% (± 0.4, range 0.5–2.3%). Affected subjects had a mean percent reticulocyte count of 9.7% (± 2.6, range 5.3–14.6%). Using this classification, the hemolytic process segregated in an autosomal dominant fashion with complete penetrance. A history of anemia (46 vs. 8%), jaundice (45 vs. 4%), red or brown urine (45 vs. 1%), and either gallstones or cholecystectomy (41 vs. 4%) was more prevalent in affected than unaffected individuals. Episodes of anemia tended to be associated with illness or stress. There was no association between the hemolytic phenotype and neuromuscular, cardiovascular, pulmonary, renal, hepatic, or endocrine disorders. Despite a mean percent reticulocyte count of 9.7% in affected individuals, the mean hemoglobin concentration was not statistically different between affected and unaffected individuals (13.5 ± 1.2 g/dL vs. 13.8 ± 1.4 g/dL, p=0.26). The MCV (96.7 ± 5.5 fL vs. 87.3 ± 5.2 fL, p<0.01) and MCHC (36.6 ± 0.6 g/dL vs. 33.8 ± 0.9 g/dL, p<0.01) were significantly elevated among affected individuals. Morphologically, target cells and stomatocytes were increased among affected individuals. Affected individuals had significantly elevated indirect bilirubin and decreased haptoglobin compared to unaffected or unrelated individuals. Serum ferritin was elevated in all age tertiles in affected individuals compared to non-affected or unrelated individuals, and 7/29 affected individuals had a serum ferritin >900 μg/L. Osmotic fragility performed on 4 affected individuals was decreased. Glycolytic enzymes, screens for unstable hemoglobins and hemoglobinopathies were normal in those tested. Conclusions: In this family study, elevated percent reticulocyte counts were used to characterize the presence of a well compensated, autosomal dominant hemolytic process associated with an elevated MCHC and decreased osmotic fragility. Clinically this condition is associated with gallstones and progressive iron loading. Features are consistent with hereditary xerocytosis. Molecular analysis is currently underway to locate the causative gene and identify the underlying mutation. Disclosures: No relevant conflicts of interest to declare.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».