Ventricular septal defect in a child with Alport syndrome: a case report

<p>Abstract</p> <p>Background</p> <p>Alport syndrome (AS) is a rare inherited disorder characterized by an inflammation of the kidneys and damage to the glomerular capillaries, ultimately leading to renal failure at an early age. To date, rare reports of cardiac involvement in AS have been described, due in the majority of cases to the higher risk of heart conduction abnormalities in these patients, at times requiring implantation of a transcutaneous pacemaker. An increased risk of hypertension is likewise commonly featured.</p> <p>Case presentation</p> <p>We report the case of a 17-year-old female affected by a very severe early form of AS. A previously unreported association of the syndrome with congenital heart disease (CHD), (in this case membranous ventricular septal defect), is also reported. A possible pathophysiological mechanism underlying the concomitant manifestation of these two disorders is suggested. Complications implicated in surgical treatment of CHD are described. Clinical and therapeutic management of AS with cardiovascular involvement are discussed, and a short literature review performed.</p> <p>Conclusions</p> <p>This first report of a cardiovascular association highlights the possible involvement of collagen mutations in the two pathologies. Even when drug-resistance appears to be responsible for the failure to control secondary hypertension in AS, clonidine may represent a safe, effective option in the normalization of high blood pressure.</p

Women and Alport syndrome

X-linked Alport syndrome (XLAS) is caused by mutations in type IV collagen causing sensorineural hearing loss, eye abnormalities, and progressive kidney dysfunction that results in near universal end-stage renal disease (ESRD) and the need for kidney transplantation in affected males. Until recent decades, the disease burden in heterozygous “carrier” females was largely minimized or ignored. Heterozygous females have widely variable disease outcomes, with some affected females exhibiting normal urinalysis and kidney function, while others develop ESRD and deafness. While the determinants of disease severity in females with XLAS are uncertain, skewing of X-chromosome inactivation has recently been found to play a role. This review will explore the natural history of heterozygous XLAS females, the determinants of disease severity, and the utility of using XLAS females as kidney donors

The role of molecular genetics in diagnosing familial hematuria(s)

Familial microscopic hematuria (MH) of glomerular origin represents a heterogeneous group of monogenic conditions involving several genes, some of which remain unknown. Recent advances have increased our understanding and our ability to use molecular genetics for diagnosing such patients, enabling us to study their clinical characteristics over time. Three collagen IV genes, COL4A3, COL4A4, and COL4A5 explain the autosomal and X-linked forms of Alport syndrome (AS), and a subset of thin basement membrane nephropathy (TBMN). A number of X-linked AS patients follow a milder course reminiscent of that of patients with heterozygous COL4A3/COL4A4 mutations and TBMN, while at the same time a significant subset of patients with TBMN and familial MH progress to chronic kidney disease (CKD) or end-stage kidney disease (ESKD). A mutation in CFHR5, a member of the complement factor H family of genes that regulate complement activation, was recently shown to cause isolated C3 glomerulopathy, presenting with MH in childhood and demonstrating a significant risk for CKD/ESKD after 40 years old. Through these results molecular genetics emerges as a powerful tool for a definite diagnosis when all the above conditions enter the differential diagnosis, while in many at-risk related family members, a molecular diagnosis may obviate the need for another renal biopsy

Clonal B cell populations in a minority of patients with Hashimoto’s thyroiditis

Background: Hashimoto’s thyroiditis (HT) is a risk factor for thyroid lymphoma, and clonal B cell populations in HT support this link. The literature on B cell clonality in HT is controversial. Aims: To identify clonal B cell populations in HT and to assess their usefulness in differentiating HT from mucosa associated lymphoid tissue (MALT) lymphoma and predicting future development of lymphoma. Methods: DNA from formalin fixed, paraffin wax embedded blocks of thyroid specimens from 10 patients with HT and two thyroid MALT lymphomas was analysed for B cell clonality by seminested polymerase chain reaction (PCR) using FRIII/LJH and FRIII/VLJH primers to amplify the IgH gene VDJ region. In one case, PCR products were sequenced. Immunohistochemistry was performed by labelled streptavidin–biotin technique using antibodies to: CD45, CD45RO, CD3, CD20, and cytokeratin. Results: The histopathological and clinical findings were characteristic of HT. Clonal bands were seen in three and a polyclonal smear pattern was seen in seven cases. The clonal bands in HT were associated with a background smear, and could not be reproduced from other blocks from the same case or from deeper sections of the same block. The clonal bands in thyroid lymphomas were not associated with a background smear and were reproducible. None of the patients with clonal B cells has developed malignant lymphoma during a follow up of 10–13 years. Conclusions: B cell clonal bands in HT have different features from those in lymphoma (non-pure and non-reproducible) and do not predict future development of lymphoma