Role of mitochondria in ataxia-telangiectasia: investigation of mitochondrial deletions and haplogroups

Ataxia-Telangiectasia [AT] is a rare human neurodegenerative autosomal recessive multisystem disease that is characterized by a wide range of features including, progressive cerebellar ataxia with onset during infancy, occulocutaneous telangiectasia, susceptibility to neoplasia, occulomotor disturbances, chromosomal instability and growth and developmental abnormalities. Mitochondrial DNA [mtDNA] has the only non-coding regions at the displacement loop [D-loop] region that contains two hypervariable segments [HVS-I and HVS-II] with high polymorphism. We investigated mt-DNA deletions and haplogroups in AT patients. In this study, 24 Iranian patients suffering from AT and 100 normal controls were examined. mt-DNA was extracted from whole blood and examined by 6 primers for existence of mitochondrial deletions. We also amplified and sequenced the mtDNA HVS-I by standard sequencing techniques. mtDNA deletions were observed in 54.1% [13/24] of patients [8.9 kb deletion in all samples, 5.0 kb in one and 7.5 kb in two patients], representing mtDNA damage which may be due to oxidative stress in mitochondria. Our results showed that there is no association between mtDNA haplogroups and AT. This data may indicate involvement of mitochondrial damage in the pathogenesis of AT

Gastrointestinal manifestations of patients with Chronic Granulomatous Disease

Chronic Granulomatous Disease [CGD] represents a group of inherited disorders of phagocytic system, manifesting recurrent infections at different sites. The present study was accomplished in order to determine the gastrointestinal manifestations of CGD patients. Fifty-seven patients [38 males and 19 females] with CGD, who had been referred to three immunodeficiency referral centers in Iran, were studied during a 24-year period [1980-2004]. The median age at the time of study was 14.5 years old [1-56 years]. The median onset age of symptoms was 5 months [1 month - 13.75 years], and that of diagnostic age was 5 years [2 months- 54.1 years], with a diagnostic delay of 33 months, on average. Seven patients were presented with acute diarrhea, 3 with oral candidiasis, and 2 with liver abscesses as the first chief complaints. Twenty-four cases [42.1%] had been complicated by gastrointestinal manifestations during their course of the disease. Of those, 12 cases [21.1%] had diarrhea, 7 [12.3%] oral candidiasis, 5 [8.8%] hepatitis, 4 [7.0%] hepatic abscess, and 2 cases [3.5%] gastric outlet obstruction. Also, failure to thrive was detected in 6 patients [10.5%]. Four patients died [7%]. CGD should be excluded in any patient with gastrointestinal manifestations especially chronic diarrhea, hepatic abscess, and gastric outlet obstruction

Report of six cases of Chediak-Higashi syndrome with regard to clinical and laboratory findings

Chediak Higashi Syndrome [CHS] is a rare, primary immunodeficiency disorder with an autosomal recessive [AR] inheritance and characterized by recurrent infection, partial occulocutaneous albinism and an accelerated phase. In this report we describe clinical and laboratory findings from 6 CHS patients. Clinical and laboratory information of six patients who were referred to our center during the last 20 years [from 1983 - 2003] were reviewed. Onset age of disease was between 3 months to 10 years. All patients had history of consanguineous parents and two patients were siblings. All patients had oculocutaneous albinism, nystagmus, recurrent infections which included upper and lower respiratory tract [U and LRT] infections, stomatitis, thrush, and skin abscesses and hepatitis. In laboratory findings, all patients had neutropenia and normal immunoglobulins and normal CD3, CD4, and CD8, CD19 Lymphocyte by flowcytometry and three of the four patients had chemotatic defect. Five patients certainly had giant granule in bone marrow neutrophil and in one patient it was equiovocal. Three patients had an accelerated phase, and for one patient bone marrow transplantation was done that was tolerated well and had been well after 7 years. We emphasize the need for early diagnosis on basis of characteristic facies and diagnostic laboratory examinations and early bone marrow transplantation [BMT] in patients

Papillon-lefe'vre syndrome: neutrophil motility and killing defect in a child with recurrent severe infections

A case of palmoplantar hyperkeratosis with periodontosis and a history of recurrent severe pyoderma, pneumonia and multiple liver abscesses is described in a 12 year old girl. The patient demonstrated neutrophil dysfunction characterized by decreased random migration and chemotaxis and defective bactericidal activity. The exact immunopathological mechanism for susceptibility to infections in Papillon-Lefe'vre syndrome patients still remains to be determined. However, the mode of clinical presentation, laboratory findings and response to retinoid treatment, all support the speculation of Papillon-Lefe'vre syndrome as a primary immunologic disease with a variable defect in neutrophil motility and bactericidal activity. The pattern of clinical presentations as skin and periodontal lesions alone or with susceptibility to infection in other sites will change accordingly