ABSTRACT
BACKGROUND: Alport syndrome is a clinically and genetically heterogeneous nephropathy characterized by glomerular basement membrane lesions often associated with hearing loss and ocular anomalies. While the X-linked and the autosomal recessive forms are well known, the autosomal dominant form is not well acknowledged. METHODS: We have clinically investigated 38 patients with a diagnosis of autosomal dominant Alport syndrome belonging to eight different families. The analysis of the COL4A4 gene was performed by denaturing high performance liquid chromatography and automated DNA sequencing. RESULTS: In our cohort of patients, only 24.3% (9/37) reached end-stage renal disease, at the mean age of 51.2 years. Four patients had hearing loss (13.3%) and none ocular changes. Molecular analysis revealed eight novel private COL4A4 gene mutations: three frameshift, three missense and two splice-site mutations. CONCLUSIONS: These data indicate autosomal dominant Alport syndrome as a disease with a low risk of ocular and hearing anomalies but with a significant risk to develop renal failure although at an older age than the X-linked form. We were unable to demonstrate a genotype-phenotype correlation. Altogether, these data make difficult the differential diagnosis with the benign familial haematuria due to heterozygous mutations of COL4A4 and COL4A3, especially in young patients, and with the X-linked form of Alport syndrome in families where only females are affected. A correct diagnosis and prognosis is based on a comprehensive clinical investigation in as many family members as possible associated with a broadly formal genetic analysis of the pedigree.
Subject(s)
Collagen Type IV/genetics , Mutation/genetics , Nephritis, Hereditary/diagnosis , Nephritis, Hereditary/genetics , Aged , Diagnosis, Differential , Female , Frameshift Mutation/genetics , Hematuria/diagnosis , Hematuria/genetics , Heterozygote , Humans , Male , Middle Aged , Mutation, Missense/genetics , Pedigree , Polymorphism, Genetic/genetics , PrognosisABSTRACT
Chronic granulomatous disease (CGD) is a rare genetically determined immunodeficiency. Neutrophils from CGD patients show a defective killing of phagocytosed fungi and bacteria, due not only to an impairment in oxidative burst, but also to absence of normal pH value within phagocytic vacuole following phagocytosis. Because a weak base such as amantadine could potentially reverse these pH abnormalities, the authors used this drug to treat 2 CGD patients. They observed modifications of both phagosomal pH and killing activity on their neutrophils compared to those of healthy controls. Since the drug has been employed, the patients have not developed new infections, suggesting a role of amantadine as a part of CGD prophylactic regimen. These results suggest the opportunity of testing the drug in larger studies.