Human metapneumovirus infection in young children hospitalized with acute respiratory tract disease: virological and clinical features

BACKGROUND: Human metapneumovirus (hMPV) is an emerging virus associated with acute respiratory tract infections (ARIs) in young children. OBJECTIVES: To evaluate virologic and clinical features of hMPV infection during 2 consecutive winter-spring seasons. METHODS: Nasal washes were obtained from children younger than 5 years of age hospitalized for ARI. Specimens were tested for hMPV by reverse transcription-polymerase chain reaction. The hMPV F gene amplification products were sequenced, and phylogenetic trees were constructed. RESULTS: A high incidence of hMPV infection (25.3%) was observed during the 2005-2006 winter-spring season, whereas a much lower rate of infection (4.7%) during the following season was found. Phylogenetic analysis revealed that, during the 2 seasons, 60.4% of the hMPV detected were A2a, 22.9% were A2b, 4.2% were B1, and 12.5% were B2. hMPV A1 strains were not detected in any tested specimen. Clinical diagnosis was bronchiolitis in 57.1%; pneumonia in 25%; and a upper respiratory tract illness in 17.8%. Bronchiolitis was more frequent in children less than 1 year of age (80%) than in children more than 1 year of age (30.8%) (P < 0.05). When hMPV was found frequently, the hMPV spread overlapped with that of respiratory syncytial virus (RSV) and hMPV/RSV coinfections were common events (19 of 39; 48.7%). hMPV/RSV-coinfected children developed pneumonia more frequently than hMPV-infected patients (57.9% versus 20%) but no differences in disease severity (gauged by duration of hospitalization and requirement of oxygen) were observed. CONCLUSIONS: These results provide further evidence of the importance of hMPV as a pathogen associated with ARI in young children. Involvement of hMPV/RSV coinfection in cases of pneumonia is suspecte

Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene.

BACKGROUND: Alport syndrome is a clinically and genetically heterogeneous nephropathy. The majority of cases are transmitted as an X-linked semidominant condition due to COL4A5 mutations. In this form males are more severely affected than females. Less than 10% of cases are autosomal recessive due to mutation in either COL4A3 or COL4A4. In this rarer form, both males and females are severely affected. Only two cases of autosomal-dominant Alport syndrome have been reported, one due to a COL4A3 mutation and the other due to a COL4A4 mutation. Because of the paucity of the reported families, the natural history of autosomal-dominant Alport syndrome is mostly unknown. METHODS: Four families with likely autosomal-dominant Alport syndrome were investigated. COL4A3 and COL4A4 genes were analyzed by denaturing high-performance liquid chromatography (HPLC). Automated sequencing was performed to identify the underlying mutation. RESULTS: Two families had a mutation in the COL4A4 gene and two in the COL4A3. Accurate clinical evaluation of family members showed interesting results. Affected individuals (22 persons) had a wide range of phenotypes from end-stage renal disease (ESRD) in the fifth decade to a nonprogressive isolated microhematuria. Finally, three heterozygous individuals (90, 22 and 11 years old, respectively) were completely asymptomatic. CONCLUSION: This paper demonstrated that patients affected by autosomal-dominant Alport syndrome have a high clinical variability. Moreover, a reduced penetrance of about 90% (3 of 25) may be considered for the assessment of recurrence risk during genetic counseling of these families

Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene.

BACKGROUND: Alport syndrome is a clinically and genetically heterogeneous nephropathy. The majority of cases are transmitted as an X-linked semidominant condition due to COL4A5 mutations. In this form males are more severely affected than females. Less than 10% of cases are autosomal recessive due to mutation in either COL4A3 or COL4A4. In this rarer form, both males and females are severely affected. Only two cases of autosomal-dominant Alport syndrome have been reported, one due to a COL4A3 mutation and the other due to a COL4A4 mutation. Because of the paucity of the reported families, the natural history of autosomal-dominant Alport syndrome is mostly unknown. METHODS: Four families with likely autosomal-dominant Alport syndrome were investigated. COL4A3 and COL4A4 genes were analyzed by denaturing high-performance liquid chromatography (HPLC). Automated sequencing was performed to identify the underlying mutation. RESULTS: Two families had a mutation in the COL4A4 gene and two in the COL4A3. Accurate clinical evaluation of family members showed interesting results. Affected individuals (22 persons) had a wide range of phenotypes from end-stage renal disease (ESRD) in the fifth decade to a nonprogressive isolated microhematuria. Finally, three heterozygous individuals (90, 22 and 11 years old, respectively) were completely asymptomatic. CONCLUSION: This paper demonstrated that patients affected by autosomal-dominant Alport syndrome have a high clinical variability. Moreover, a reduced penetrance of about 90% (3 of 25) may be considered for the assessment of recurrence risk during genetic counseling of these families

Cardiomyopathy in a male patient with neutropenia and growth delay.

Neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, ranging from severe (<500 neutrophils/mm(3)) to mild (500-1500 neutrophils/mm(3)), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections whose severity is roughly inversely proportional to the circulating neutrophil counts.When neutropenia is detected, an attempt should be made to establish the etiology, and to distinguish acquired forms (the most frequent, including post viral neutropenia and autoimmune neutropenia) and congenital forms (rare disorders) that may be either isolated or part of a complex rare genetic disease. We report on a male patient initially diagnosed with isolated neutropenia who later turned out to be affected with Barth syndrome, a rare complex inherited disorder

Locus heterogeneity of Dent's disease: OCRL1 and TMEM27 genes in patients with no CLCN5 mutations

Dent's disease is an X-linked renal tubulopathy caused by mutations mainly affecting the CLCN5 gene. Defects in the OCRL1 gene, which is usually mutated in patients with Lowe syndrome, have recently been shown to lead to a Dent-like phenotype, called Dent's disease 2. About 25% of Dent's disease patients do not carry CLCN5/OCRL1 mutations. The CLCN4 and SLC9A6 genes have been investigated, but no mutations have been identified. The recent discovery of a novel mediator of renal amino acid transport, collectrin (the TMEM27 gene), may provide new insight on the pathogenesis of Dent's disease. We studied 31 patients showing a phenotype resembling Dent's disease but lacking any CLCN5 mutations by direct sequencing of the OCRL1 and TMEM27 genes. Five novel mutations, L88X, P161HfsX167, F270S, D506N and E720D, in the OCRL1 gene, which have not previously been reported in patients with Dent's or Lowe disease, were identified among 11 patients with the classical Dent's disease phenotype. No TMEM27 gene mutations were discovered among 26 patients, 20 of whom had an incomplete Dent's disease phenotype. Our findings confirm that OCRL1 is involved in the functional defects characteristic of Dent's disease and suggest that patients carrying missense mutations in exons where many Lowe mutations are mapped may represent a phenotypic variant of Lowe syndrome