The results of the first 3 years' collaboration of the Italian Registry of Paediatric Chronic Per... more The results of the first 3 years' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986)(1987)(1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1 : 20.8 dialysismonths); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. The incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%.
The POU1F1 gene encodes a transcription factor that is important for the development and differen... more The POU1F1 gene encodes a transcription factor that is important for the development and differentiation of the cells producing GH, prolactin, and TSH in the anterior pituitary gland. Patients with POU1F1 mutations show a combined pituitary hormone deficiency with low or absent levels of GH, prolactin, and TSH. Fourteen mutations have been reported in the POU1F1 gene up to now. These genetic lesions can be inherited either in an autosomal dominant or an autosomal recessive mode. We report on the first Italian patient, a girl, affected by combined pituitary hormone deficiency. The patient was found to be positive for congenital hypothyroidism (with low TSH levels) at neonatal screening. Substitutive therapy was started, but subsequent growth was very poor, although psychomotor development was substantially normal. Hospitalized at 10 mo she showed hypotonic crises, growth retardation, delayed bone age, and facial dysmorphism. In addition to congenital hypothyroidism, GH and prolactin deficiencies were found. Mutation DNA analysis of the patient's POU1F1 gene identified the novel Q167K amino acid change at the heterozygous level. The highly con-served Q167 residue is located in the POU-specific domain. No mutation was detected in the other allele. DNA analysis in the proband's parents did not identify this amino acid substitution, suggesting a de novo genetic lesion. From these data it can be hypothesized that the Q167K mutation has a dominant negative effect. Abbreviations CPHD, combined pituitary hormone deficiency PRL, prolactin FT 4 , free thyroxine T 4 , total thyroxine u-TSH, ultra thyroid-stimulating-hormone US, upper segment LS, lower segment IGF-BP3, insulin growth factor-binding protein 3 FT 3 , free triiodothyronine POU-S, POU-specific POU-D, POU-homeo
Little is known about the prescription pattern of antihypertensive drugs for children with impair... more Little is known about the prescription pattern of antihypertensive drugs for children with impaired kidney function. We have therefore documented the use of antihypertensive drugs in this patient group by evaluating the Italian pediatric population-based registry of patients with chronic kidney disease on conservative treatment (ItalKid) from 1995 to 2003. In 1995, prescriptions written for antihypertensive drugs for use by children were approximately equally divided among drugs blocking the renin-angiotensin system and calcium channel blockers (38 vs. 43% of all prescriptions), followed by "-blockers and diuretics (15 and 4%, respectively). During subsequent years the proportion of prescriptions for drugs blocking the renin-angiotensin system increased (2003: 61%; p<0.001) and that of calcium channel blockers decreased (2003: 18%, p<0.001). In 1995, blockers of the renin-angiotensin system were prescribed, either as monotherapy or in combination, in 53% of the patients, but the relative frequency of the patients prescribed these drugs increased up to 83% in 2003 (p<0.0005). In conclusion, physicians caring for Italian children with impaired kidney function are increasingly prescribing drugs blocking the renin-angiotensin system.
Acute renal failure developed during the first 3 days after birth in a newborn subsequently diagn... more Acute renal failure developed during the first 3 days after birth in a newborn subsequently diagnosed with hypoxanthine-guanine-phosphoribosyl-transferase (HPRT) deficiency. Fluid infusion and allopurinol therapy normalised renal function and serum uric acid levels. Only a few cases of acute renal failure due to acute hyperuricemic nephropathy related to HPRT deficiency have previously been reported in infants, and there are no reported cases in newborns as young as 3 days old.
A significant number of patients affected by autosomal recessive primary distal renal tubular aci... more A significant number of patients affected by autosomal recessive primary distal renal tubular acidosis (dRTA) manifest sensorineural hearing loss (SNHL). Mutations in ATP6V1B1 are associated with early onset SNHL, whereas ATP6V0A4 mutations have been described in dRTA and late-onset SNHL. Enlarged vestibular aqueduct (EVA) was described in patients with recessive dRTA and SNHL, and recently, this abnormality has been associated with mutations in the ATP6V1B1 gene. In our study, we evaluated the presence of inner-ear abnormalities in four patients affected by dRTA and SNHL, characterized by molecular analysis. Two patients affected by severe dRTA with early onset SNHL showed the same mutation in the ATP6V1B1 gene and bilateral EVA with a different degree of severity. The other two presented similar clinical manifestations of dRTA and different mutations in the ATP6V0A4 gene: one patient, showing EVA, developed an early SNHL, whereas in the other one, the SNHL appeared in the second decade of life and the vestibular aqueduct was normal. Our study confirms the association of EVA and mutations in the ATP6V1B1 gene and demonstrates that mutations in the ATP6V0A4 gene can also be associated with EVA probably only when the SNHL has an early onset. The pathophysiology of SNHL and EVA are still to be defined.
In this report we present the case of a 15-month-old girl with hyponatraemic-hypertensive syndrom... more In this report we present the case of a 15-month-old girl with hyponatraemic-hypertensive syndrome (HHS) caused by stenosis of the left renal artery. On sonographic examination the contralateral non-stenotic kidney appeared enlarged and with cortical hyperechogenicity mimicking a parenchymal lesion. After successful percutaneous transluminal angioplasty, when the girl became normotensive, her serum electrolyte and acid-base balance became normal within a few days. The contralateral non-stenotic kidney hyperechogenicity also disappeared, but only after a period of 6 months, suggesting parenchymal damage due to tubulointerstitial injury, even though reversible. Our case confirms that renovascular hypertension may rarely also be present with HHS in children and that metabolic and morphological alterations are reversible after the resolution of arterial stenosis.
Hypokalemia represents a rare cause of rhabdomyolysis. Some reports have described a few adult pa... more Hypokalemia represents a rare cause of rhabdomyolysis. Some reports have described a few adult patients affected by Bartter's syndrome and Gitelman's syndrome with rhabdomyolysis due to severe hypokalemia. We report the first pediatric patient with Bartter's syndrome in whom rhabdomyolysis developed when her plasma potassium level was less than 2 mEq/l. Prompt intravenous fluid and potassium prevented tubular damage and acute renal failure. We recommend determining serum creatine phosphokinase in all patients affected by Bartter's syndrome and profound hypokalemia.
Peritoneal and extracorporeal dialysis are used to treat newborns affected by inborn errors of me... more Peritoneal and extracorporeal dialysis are used to treat newborns affected by inborn errors of metabolism to minimize the effects of the acute accumulation of neurotoxic metabolites that can produce irreversible and severe neurological damage and even death. In recent papers, extracorporeal dialysis has been described as more effective than peritoneal dialysis in improving the prognosis in newborns with inborn errors of metabolism and hyperammonemia.
We report an infant with neonatal nonketotic hyperglycinemia (NKH), diagnosed early and treated w... more We report an infant with neonatal nonketotic hyperglycinemia (NKH), diagnosed early and treated with dextromethorphan (DM) and sodium benzoate therapy from the 65th hour of life. Initially the patient responded to treatment showing clinical and electroencephalographic improvement: myoclonic jerks disappeared, muscular tone, reactivity to stimuli and spontaneous movements increased, assisted ventilation was no longer necessary and bottle feeding was initiated successfully; on EEG the suppression-burst pattern disappeared and the background activity was well-organized. At three months of age he developed flexor spasms and hypsarrhythmia. In spite of increasing doses of DM as high as 40 mg/kg/day and persistent therapy with sodium benzoate the child progressively deteriorated and died at the age of 5 months and 7 days. We stress that the adverse clinical course occurred in our patient even though DM and sodium benzoate therapy was started much earlier than in other reported cases. It is possible that prenatal brain damage and probable genetic variants (i.e. absent or minimal residual enzymatic activity and interindividual variations in DM metabolism) affect the response to therapy.
We provide a molecular and pathophysiological characterization of an 11-year-old male patient, wi... more We provide a molecular and pathophysiological characterization of an 11-year-old male patient, with a diagnosis of renal hypodysplasia, cysts and chronic renal failure. Although previously normoglycaemic and with a negative familial history for diabetes mellitus, he developed fasting hyperglycaemia within 12 months of the start of treatment with recombinant human growth hormone (rhGH). Direct sequencing of the HNF1β gene revealed a de novo heterozygous mutation in exon 2, c.535delC [Pro118LeuX7] + [=]. The appearance of fasting hyperglycaemia following rhGH treatment in children with renal cystic hypodysplasia suggests that investigation of the HNF1β gene is warranted, even when familial history is negative for diabetes. This is particularly important in regard to genetic counselling.
Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or di... more Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilation of precalyceal collecting tubules. Although its pathogenesis is unknown, the association with various congenital diseases suggests that it could be a developmental disorder. In addition to the typical clinical features of nephrocalcinosis and urolithiasis, patients with MSK show tubular function defects of acidification and concentration. These are considered to be secondary to morphological changes of collecting tubules. Primary distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H(+) ions in the intercalated cells of the collecting duct required for final excretion of fixed acids. Both autosomal dominant and autosomal recessive forms have been described, the latter is also associated with sensorineural hearing loss. We report two patients presenting with dRTA, late sensorineural hearing loss and MSK, in whom molecular investigations demonstrated the presence of mutations of the H(+) proton pump ATP6V1B1 and ATP6V0A4 genes. These observations, including a previous description of a similar case in the literature, indicate that MSK could be a consequence of the proton pump defect, thus can potentially provide new insights into the pathogenesis of MSK.
We retrospectively analyzed etiological, pathological and clinical features of the patients with ... more We retrospectively analyzed etiological, pathological and clinical features of the patients with hemolytic uremic syndrome (HUS) observed in the Pediatric Nephrology Unit at AOU Meyer of Florence. From January 1997 to December 2008, 22 cases were identified, with an annual incidence of 0.05 cases per 100,000 inhabitants, and 0.34 cases per 100,000 children &amp;amp;amp;amp;amp;amp;amp;amp;lt;15 years old. 60% of the patients were D+ and 40% were D-, with an age distribution from 12 days to 13 years. Twenty patients (90%) had oligoanuria, lasting 6.4 ± 4 days for D+ patients versus 11.8 ± 4 days for D- patients. The development of chronic kidney disease positively correlates with the initial blood pressure value, the length of oligoanuria, and hospitalization. Microbiological investigations showed an association of D+HUS with different strains of Shiga toxin-producing Escherichia coli in 54% of the cases. D-HUS was associated with complement factor H deficiency in one patient. In the other cases, the triggering factors were pertussis, urinary tract infections and upper airway infections. While clinical and prognostic features correspond with literature data, in Tuscany the annual incidence is lower, and the percentage of D-HUS patients is higher than that observed in other studies.
Background: Little information on the management and long-term follow-up of patients with biallel... more Background: Little information on the management and long-term follow-up of patients with biallelic mutations in the chloride channel gene CLCNKB is available.
We have recently observed a large pedigree with a new rare autosomal dominant spastic paraparesis... more We have recently observed a large pedigree with a new rare autosomal dominant spastic paraparesis. In three subsequent generations, 13 affected individuals presented with bilateral cataracts, gastroesophageal reflux with persistent vomiting, and spastic paraparesis with amyotrophy. Bilateral cataracts occurred in all affected individuals, with the exception of one patient who presented with a chorioretinal dystrophy, whereas clinical signs of spastic paraparesis showed a variable expressivity. Using a genomewide mapping approach, we mapped the disorder to the long arm of chromosome 10 on band q23.3-q24.2, in a 12-cM chromosomal region where additional neurologic disorders have been localized. The spectrum of phenotypic manifestations in this family is reminiscent of a smaller pedigree, reported recently, confirming the possibility of a new syndrome. Finally, the anticipation of symptoms suggests that an unstable trinucleotide repeat may be responsible for the condition.
Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic ... more Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76% of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D(-) but STEC(+) patients have a significantly better prognosis.
The results of the first 3 years' collaboration of the Italian Registry of Paediatric Chronic Per... more The results of the first 3 years' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986)(1987)(1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1 : 20.8 dialysismonths); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. The incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%.
The POU1F1 gene encodes a transcription factor that is important for the development and differen... more The POU1F1 gene encodes a transcription factor that is important for the development and differentiation of the cells producing GH, prolactin, and TSH in the anterior pituitary gland. Patients with POU1F1 mutations show a combined pituitary hormone deficiency with low or absent levels of GH, prolactin, and TSH. Fourteen mutations have been reported in the POU1F1 gene up to now. These genetic lesions can be inherited either in an autosomal dominant or an autosomal recessive mode. We report on the first Italian patient, a girl, affected by combined pituitary hormone deficiency. The patient was found to be positive for congenital hypothyroidism (with low TSH levels) at neonatal screening. Substitutive therapy was started, but subsequent growth was very poor, although psychomotor development was substantially normal. Hospitalized at 10 mo she showed hypotonic crises, growth retardation, delayed bone age, and facial dysmorphism. In addition to congenital hypothyroidism, GH and prolactin deficiencies were found. Mutation DNA analysis of the patient's POU1F1 gene identified the novel Q167K amino acid change at the heterozygous level. The highly con-served Q167 residue is located in the POU-specific domain. No mutation was detected in the other allele. DNA analysis in the proband's parents did not identify this amino acid substitution, suggesting a de novo genetic lesion. From these data it can be hypothesized that the Q167K mutation has a dominant negative effect. Abbreviations CPHD, combined pituitary hormone deficiency PRL, prolactin FT 4 , free thyroxine T 4 , total thyroxine u-TSH, ultra thyroid-stimulating-hormone US, upper segment LS, lower segment IGF-BP3, insulin growth factor-binding protein 3 FT 3 , free triiodothyronine POU-S, POU-specific POU-D, POU-homeo
Little is known about the prescription pattern of antihypertensive drugs for children with impair... more Little is known about the prescription pattern of antihypertensive drugs for children with impaired kidney function. We have therefore documented the use of antihypertensive drugs in this patient group by evaluating the Italian pediatric population-based registry of patients with chronic kidney disease on conservative treatment (ItalKid) from 1995 to 2003. In 1995, prescriptions written for antihypertensive drugs for use by children were approximately equally divided among drugs blocking the renin-angiotensin system and calcium channel blockers (38 vs. 43% of all prescriptions), followed by "-blockers and diuretics (15 and 4%, respectively). During subsequent years the proportion of prescriptions for drugs blocking the renin-angiotensin system increased (2003: 61%; p<0.001) and that of calcium channel blockers decreased (2003: 18%, p<0.001). In 1995, blockers of the renin-angiotensin system were prescribed, either as monotherapy or in combination, in 53% of the patients, but the relative frequency of the patients prescribed these drugs increased up to 83% in 2003 (p<0.0005). In conclusion, physicians caring for Italian children with impaired kidney function are increasingly prescribing drugs blocking the renin-angiotensin system.
Acute renal failure developed during the first 3 days after birth in a newborn subsequently diagn... more Acute renal failure developed during the first 3 days after birth in a newborn subsequently diagnosed with hypoxanthine-guanine-phosphoribosyl-transferase (HPRT) deficiency. Fluid infusion and allopurinol therapy normalised renal function and serum uric acid levels. Only a few cases of acute renal failure due to acute hyperuricemic nephropathy related to HPRT deficiency have previously been reported in infants, and there are no reported cases in newborns as young as 3 days old.
A significant number of patients affected by autosomal recessive primary distal renal tubular aci... more A significant number of patients affected by autosomal recessive primary distal renal tubular acidosis (dRTA) manifest sensorineural hearing loss (SNHL). Mutations in ATP6V1B1 are associated with early onset SNHL, whereas ATP6V0A4 mutations have been described in dRTA and late-onset SNHL. Enlarged vestibular aqueduct (EVA) was described in patients with recessive dRTA and SNHL, and recently, this abnormality has been associated with mutations in the ATP6V1B1 gene. In our study, we evaluated the presence of inner-ear abnormalities in four patients affected by dRTA and SNHL, characterized by molecular analysis. Two patients affected by severe dRTA with early onset SNHL showed the same mutation in the ATP6V1B1 gene and bilateral EVA with a different degree of severity. The other two presented similar clinical manifestations of dRTA and different mutations in the ATP6V0A4 gene: one patient, showing EVA, developed an early SNHL, whereas in the other one, the SNHL appeared in the second decade of life and the vestibular aqueduct was normal. Our study confirms the association of EVA and mutations in the ATP6V1B1 gene and demonstrates that mutations in the ATP6V0A4 gene can also be associated with EVA probably only when the SNHL has an early onset. The pathophysiology of SNHL and EVA are still to be defined.
In this report we present the case of a 15-month-old girl with hyponatraemic-hypertensive syndrom... more In this report we present the case of a 15-month-old girl with hyponatraemic-hypertensive syndrome (HHS) caused by stenosis of the left renal artery. On sonographic examination the contralateral non-stenotic kidney appeared enlarged and with cortical hyperechogenicity mimicking a parenchymal lesion. After successful percutaneous transluminal angioplasty, when the girl became normotensive, her serum electrolyte and acid-base balance became normal within a few days. The contralateral non-stenotic kidney hyperechogenicity also disappeared, but only after a period of 6 months, suggesting parenchymal damage due to tubulointerstitial injury, even though reversible. Our case confirms that renovascular hypertension may rarely also be present with HHS in children and that metabolic and morphological alterations are reversible after the resolution of arterial stenosis.
Hypokalemia represents a rare cause of rhabdomyolysis. Some reports have described a few adult pa... more Hypokalemia represents a rare cause of rhabdomyolysis. Some reports have described a few adult patients affected by Bartter's syndrome and Gitelman's syndrome with rhabdomyolysis due to severe hypokalemia. We report the first pediatric patient with Bartter's syndrome in whom rhabdomyolysis developed when her plasma potassium level was less than 2 mEq/l. Prompt intravenous fluid and potassium prevented tubular damage and acute renal failure. We recommend determining serum creatine phosphokinase in all patients affected by Bartter's syndrome and profound hypokalemia.
Peritoneal and extracorporeal dialysis are used to treat newborns affected by inborn errors of me... more Peritoneal and extracorporeal dialysis are used to treat newborns affected by inborn errors of metabolism to minimize the effects of the acute accumulation of neurotoxic metabolites that can produce irreversible and severe neurological damage and even death. In recent papers, extracorporeal dialysis has been described as more effective than peritoneal dialysis in improving the prognosis in newborns with inborn errors of metabolism and hyperammonemia.
We report an infant with neonatal nonketotic hyperglycinemia (NKH), diagnosed early and treated w... more We report an infant with neonatal nonketotic hyperglycinemia (NKH), diagnosed early and treated with dextromethorphan (DM) and sodium benzoate therapy from the 65th hour of life. Initially the patient responded to treatment showing clinical and electroencephalographic improvement: myoclonic jerks disappeared, muscular tone, reactivity to stimuli and spontaneous movements increased, assisted ventilation was no longer necessary and bottle feeding was initiated successfully; on EEG the suppression-burst pattern disappeared and the background activity was well-organized. At three months of age he developed flexor spasms and hypsarrhythmia. In spite of increasing doses of DM as high as 40 mg/kg/day and persistent therapy with sodium benzoate the child progressively deteriorated and died at the age of 5 months and 7 days. We stress that the adverse clinical course occurred in our patient even though DM and sodium benzoate therapy was started much earlier than in other reported cases. It is possible that prenatal brain damage and probable genetic variants (i.e. absent or minimal residual enzymatic activity and interindividual variations in DM metabolism) affect the response to therapy.
We provide a molecular and pathophysiological characterization of an 11-year-old male patient, wi... more We provide a molecular and pathophysiological characterization of an 11-year-old male patient, with a diagnosis of renal hypodysplasia, cysts and chronic renal failure. Although previously normoglycaemic and with a negative familial history for diabetes mellitus, he developed fasting hyperglycaemia within 12 months of the start of treatment with recombinant human growth hormone (rhGH). Direct sequencing of the HNF1β gene revealed a de novo heterozygous mutation in exon 2, c.535delC [Pro118LeuX7] + [=]. The appearance of fasting hyperglycaemia following rhGH treatment in children with renal cystic hypodysplasia suggests that investigation of the HNF1β gene is warranted, even when familial history is negative for diabetes. This is particularly important in regard to genetic counselling.
Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or di... more Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilation of precalyceal collecting tubules. Although its pathogenesis is unknown, the association with various congenital diseases suggests that it could be a developmental disorder. In addition to the typical clinical features of nephrocalcinosis and urolithiasis, patients with MSK show tubular function defects of acidification and concentration. These are considered to be secondary to morphological changes of collecting tubules. Primary distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H(+) ions in the intercalated cells of the collecting duct required for final excretion of fixed acids. Both autosomal dominant and autosomal recessive forms have been described, the latter is also associated with sensorineural hearing loss. We report two patients presenting with dRTA, late sensorineural hearing loss and MSK, in whom molecular investigations demonstrated the presence of mutations of the H(+) proton pump ATP6V1B1 and ATP6V0A4 genes. These observations, including a previous description of a similar case in the literature, indicate that MSK could be a consequence of the proton pump defect, thus can potentially provide new insights into the pathogenesis of MSK.
We retrospectively analyzed etiological, pathological and clinical features of the patients with ... more We retrospectively analyzed etiological, pathological and clinical features of the patients with hemolytic uremic syndrome (HUS) observed in the Pediatric Nephrology Unit at AOU Meyer of Florence. From January 1997 to December 2008, 22 cases were identified, with an annual incidence of 0.05 cases per 100,000 inhabitants, and 0.34 cases per 100,000 children &amp;amp;amp;amp;amp;amp;amp;amp;lt;15 years old. 60% of the patients were D+ and 40% were D-, with an age distribution from 12 days to 13 years. Twenty patients (90%) had oligoanuria, lasting 6.4 ± 4 days for D+ patients versus 11.8 ± 4 days for D- patients. The development of chronic kidney disease positively correlates with the initial blood pressure value, the length of oligoanuria, and hospitalization. Microbiological investigations showed an association of D+HUS with different strains of Shiga toxin-producing Escherichia coli in 54% of the cases. D-HUS was associated with complement factor H deficiency in one patient. In the other cases, the triggering factors were pertussis, urinary tract infections and upper airway infections. While clinical and prognostic features correspond with literature data, in Tuscany the annual incidence is lower, and the percentage of D-HUS patients is higher than that observed in other studies.
Background: Little information on the management and long-term follow-up of patients with biallel... more Background: Little information on the management and long-term follow-up of patients with biallelic mutations in the chloride channel gene CLCNKB is available.
We have recently observed a large pedigree with a new rare autosomal dominant spastic paraparesis... more We have recently observed a large pedigree with a new rare autosomal dominant spastic paraparesis. In three subsequent generations, 13 affected individuals presented with bilateral cataracts, gastroesophageal reflux with persistent vomiting, and spastic paraparesis with amyotrophy. Bilateral cataracts occurred in all affected individuals, with the exception of one patient who presented with a chorioretinal dystrophy, whereas clinical signs of spastic paraparesis showed a variable expressivity. Using a genomewide mapping approach, we mapped the disorder to the long arm of chromosome 10 on band q23.3-q24.2, in a 12-cM chromosomal region where additional neurologic disorders have been localized. The spectrum of phenotypic manifestations in this family is reminiscent of a smaller pedigree, reported recently, confirming the possibility of a new syndrome. Finally, the anticipation of symptoms suggests that an unstable trinucleotide repeat may be responsible for the condition.
Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic ... more Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76% of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D(-) but STEC(+) patients have a significantly better prognosis.
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Papers by Ivana Pela