Allogenic hematopoietic stem cell transplantation in an Iranian patient with osteopetrosis caused by carbonic anhydrase II deficiency: A case report.

BACKGROUND: Osteopetrosis is a group of geneticall heterogeneous disorders resulting from impaired osteoclast function and bone resorption. The identification of specific genetic mutations can yield important prognostic and therapeutic implications. Herein, we present the diagnosis and successful application of hematopoietic stem cell transplantation (HSCT) in a patient with osteopetrosis caused by carbonic anhydrase II deficiency (Intermediate osteopetrosis). CASE PRESENTATION: Herein, we describe a 2.5-year-old male patient born to consanguineous parents who presented at 8-month-old with hydrocephaly, brain shunt, and developmental delay. Later at 9 months old, he was found to have eye disorder such as nystagmus, fracture of the elbow, abnormal skeletal survey, normal cell blood count (CBC), and severe hypocellularity in the bone marrow. Further evaluation showed renal tubular acidosis type 2. Whole-exome sequencing revealed a pathogenic homozygous variant in intron 2 of the carbonic anhydrase 2 gene (CA2) gene (c.232 + 1 G>T). The diagnosis of intermediate autosomal recessive osteopetrosis was established, and allogenic HSCT from his mother, a full-matched related donor (MRD), was planned. The conditioning regimen included Busulfan, Fludarabine, and Rabbit anti-thymocyte globulin. Cyclosporine and Mycophenolate Mofetil were used for graft-versus-host-disease prophylaxis. He Engrafted on day +13, and 95% chimerism was achieved. He is currently doing well without immunosuppressive therapy, now 12 months post HSCT, with normal calcium level and improving visual quality and FISH analysis revealed complete donor chimerism. DISCUSSION: HSCT could be a promising curative treatment for intermediate osteopetrosis and can provide long-term survival. Ongoing challenges in various aspects of HSCT remain to be addressed.

Prevalence of Anemia and its Relation with Shwachman Score in Children with Cystic Fibrosis.

Background: Cystic fibrosis is a chronic and progressive genetic disease with a worldwide prevalence. As the disease progresses, symptoms develop, and make its management more challenging. Accumulating evidence suggests that early diagnosis of CF can significantly contribute to preventing reported nutritional problems including anemia, vitamin deficiencies, and hypoalbuminemia. This cross-sectional study was conducted to assess disease severity in cystic fibrosis patients using the Shwachman-Kulczycki score, as well as to determine its relation with anemia and vitamin D deficiency. Materials and Methods: Clinical and CF-related laboratory data were collected from the medical records of 57 CF patients with a definitive diagnosis. At the time of diagnosis, physicians performed simultaneous, blood sampling and scoring of patients using the Shwachman scoring system. Results: The mean age of patients was 16.12±6.48 years. Total scores of 86-100, 71-85, 56-70, 41-55, and <40, were reported in 5.4%, 7.1%, 14.3%, 14.3%, and 58.9% of CF patients, respectively. A significant correlation was found between disease severity and patients' age (P=0.02). The analysis also showed that the disease severity was significantly higher in anemic patients when compared to non-anemics (p =0.006). Based on the results, 33 patients with normochromic, 11 patients with microcytic, and 6 patients with macrocytic anemia were diagnosed in this study. We did not find a significant difference between disease severity and vitamin D levels (P=0.150). Conclusion: The scoring system used in the current study could reflect properly the clinical status of CF patients. However, simultaneous use of various methods using a larger sample size for comparison of results is suggested to improve the accuracy of findings.

Clinical and genetic characteristics of hemoglobin H disease in Iran.

Hemoglobin H (Hb H) disease is a subtype of α-thalassemia caused by deletional and/or non-deletional mutations in three alpha-globin genes in which the various genotypes determine the disease severity. This study was aimed to investigate the frequency of alpha gene mutations and genotypes and their correlation with hematological and clinical characteristics in Iran. Among 202 patients diagnosed with Hb H disease through a national study in Iran according to standard methods, we had access to the hematologic and clinical findings and genetic data of 101 patients in whom genetic study was performed. Genomic DNA from peripheral blood was extracted and analyzed for identification of α-globin gene mutations using Multiplex Gap Polymerase Chain Reaction, Reverse Hybridization Assay, and finally Direct DNA Sequencing method. Twenty-one different mutations and thirty genotypes were detected in 101 patients with Hb H disease. In total, 39 patients (38.6%) were deletional and 62 patients (61.4%) were non-deletional type of the disease. The --MED mutation was highly prevalent in almost half of the patients (56.4%). Among various genotypes, -MED/-a3.7 (29.7%) and -α20.5/-α5NT (6.9%) were the most prevalent genotypes found in the studied group. Patients with non-deletional type presented with more severe hematological and clinical findings. Hb H percentage and serum ferritin levels were significantly higher in non-deletional patients in comparison to the deletional group (p < 0.05). 12 (11.9%) and 40 (39.6%) out of 101 patients were on regular and occasional transfusions, respectively. 83% of those with regular transfusion belonged to the non-deletional group. Among transfusion-dependent patients, -MED/αCSα and α20.5/-α5NT were the most common genotypes. In this study, two patients with -α20.5/αCSα and -MED/α-5NT genotypes experienced thrombotic events. This study indicated that although non-deletional genotypes of Hb H disease were responsible for more clinical severity of the disease, due to the presence of severe phenotypes even in deletional types, no definite correlation was found between genotype and phenotype.