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Background/aim: Alport syndrome is a hereditary glomerulonephritis, X-linked in 85% of the cases. This form is associated with mutations in the COL4A5 gene which encodes the alpha5 chain of type IV collagen. We have performed the mutational analysis of the COL4A5 gene in a Spanish family with X-linked Alport syndrome., Methods: We have analyzed three polymorphic markers close to the gene to confirm the X chromosome linkage. By means of the PCR technique, we have screened the 51 exons of the gene., Results: The segregation of the alleles from the analyzed markers was in agreement with the X linkage. Direct sequencing of PCR-amplified products has shown a CCT-to-CTT change in exon 25, resulting in substitution of a proline for a leucine at position 619 of the polypeptide chain (nucleotide 2058)., Conclusions: Although proline is considered a nonconserved amino acid, it is essential, upon hydroxylation, in the maintenance of a stable alpha chain triple-helix collagen. Furthermore, the change cosegregates with the disease in all affected members of the family, not being present in 80 control chromosomes. This represents a new mutation in the COL4A5 gene found in the Spanish population., (Copyright 2002 S. Karger AG, Basel)

Fifty five patients with Schöelein-Henoch nephropathy were reviewed. These patients were divided into five groups according to the clinical picture initially presented: 1. Hematuria with proteinuria. 2. Hematuria with nephrotic syndrome. 3. Isolated hematuria. 4. Hematuria, nephrotic syndrome and renal failure. 5. Proteinuria. From a histopathological point of view, they were classified into six groups according to ISKDC criteria. A strong correlation was found between clinical presentation and histological lesion. The worst prognosis corresponded to patients with nephrotic syndrome and renal failure, whose biopsy revealed more than 75% of glomeruli with epithelial crescents.

Clinical and radiological studies of seven patients with autosomic recessive malignant osteopetrosis are presented. Diagnosis was established before the age of 3 months in six cases and at 7 months in one. In all cases the presenting signs were pallor and hepatosplenomegaly with associated neurological involvement in five. All patients had normocytic normochromic anemia, leucopenia and thrombocytopenia with features of extramedullary hematopoiesis. Radiological studies revealed increase in the density of bones with "mask" appearance of facial bones and diminished size of optic foramina. Long bones showed absence of normal trabeculae and anomalies in modeling with methaphiseal bands and "bone within bone" images. There was hypocalcemia and hypophosphatemia with slight increases in alkaline phosphatase; parathormone was normal. Clinical course was characterized by progressive pancytopenia, recurrent infections and neurological deterioration with convulsions, nistagmus and optic atrophy. Five out of the seven patients died after a median of 3 months, due to infections or haemorrhage. The patient diagnosed at 7 months of age presented bilateral optic atrophy and moderate anemia; no other complications appeared after 2 year follow-up. Histological findings included substitution of bone marrow by chondro-osseous tissue; focal obsteoblastic and osteoclastic activity in calcified cartilage, and myeloid metaplasia in liver, spleen, lymph nodes and kidneys. The lesions are in agreement with the concept of a defect in bone formation-resorbtion balance; dysfunction of both osteoclasts and osteocytes is implicated in the pathogenesis. Unlike experimental disease, osteopetrosis in man is probably an heterogeneous disease and appropriate therapy should be individualized. Nevertheless, at present, the only favorable results have been obtained with bone-marrow transplantation.

Authors describe initial characteristics, clinical course and response to treatment of 13 children, aged from eight months to nine years, with acquired aplastic anaemia. Six of the children had been exposed to products with potential bone-marrow toxicity: chloranphenicol (1), pirazolones (3) and insecticides (2). Pancytopenia was severe in twelve and moderate in one. Five patients with severe aplastic anaemia were given antilymphocytic (2) or antithymocytic (3) (ATG) gammaglobulins; two of those treated with ATG responded after two and five months respectively and there was no response in the other three. Twelve patients were given androgen treatment (oxymetholone or nandrolone decanoate): four, two of whom previously had received ATG, followed a favorable course. None of the severe initial pancytopenic patients responded to androgen single agent treatment. No marrow transplant was performed in any of the children. Eight of the thirteen patients died one to 37 months after onset (median, 6 months) and five (38%) are alive after 21 months to 10 years, corresponding to two patients with moderate and three with severe initial pancytopenia. Importance of an appropriate supportive treatment during initial stages of the disease and the probable efficacy or immunosupressive treatment in certain patients must be underlined.