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1.
J Hum Genet ; 64(9): 885-890, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270375

RESUMO

Pediatric hypertension can cause hypertensive emergencies, including hemorrhagic stroke, contributing to rare but serious childhood morbidity and mortality. Renovascular hypertension (RVH) is one of the major causes of secondary hypertension in children. Grange syndrome (MIM#602531) is a rare disease characterized by multiple stenosis or occlusion of the renal, abdominal, coronary, and cerebral arteries, which can cause phenotypes of RVH and fibromuscular dysplasia (MIM#135580). We report the case of a 7-year-old girl with Grange syndrome who showed RVH and multiple seizure episodes. At 1 year of age, she experienced seizures and sequential hemiparesis caused by a left thalamic hemorrhage without cerebral vascular anomalies. Chronic hypertension was observed, and abdominal computed tomography angiography showed characteristic bilateral renal artery stenosis. Whole-exome sequencing revealed a novel homozygous pathogenic variant in the YY1AP1 gene (NM_001198903.1: c.1169del: p.Lys390Argfs*12). Biallelic YY1AP1 mutations are known to cause Grange syndrome. Unlike previously reported patients, our patient presented with intracerebral hemorrhagic stroke without anomalous brain artery or bone fragility. The phenotype in our patient may help better understand this ultra-rare syndrome. Grange syndrome should be considered in patients presenting with childhood-onset hypertension and/or hemorrhagic stroke for early clinical intervention.

2.
Nat Commun ; 10(1): 2506, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175295

RESUMO

Although there are many known Mendelian genes linked to epileptic or developmental and epileptic encephalopathy (EE/DEE), its genetic architecture is not fully explained. Here, we address this incompleteness by analyzing exomes of 743 EE/DEE cases and 2366 controls. We observe that damaging ultra-rare variants (dURVs) unique to an individual are significantly overrepresented in EE/DEE, both in known EE/DEE genes and the other non-EE/DEE genes. Importantly, enrichment of dURVs in non-EE/DEE genes is significant, even in the subset of cases with diagnostic dURVs (P = 0.000215), suggesting oligogenic contribution of non-EE/DEE gene dURVs. Gene-based analysis identifies exome-wide significant (P = 2.04 × 10-6) enrichment of damaging de novo mutations in NF1, a gene primarily linked to neurofibromatosis, in infantile spasm. Together with accumulating evidence for roles of oligogenic or modifier variants in severe neurodevelopmental disorders, our results highlight genetic complexity in EE/DEE, and indicate that EE/DEE is not an aggregate of simple Mendelian disorders.


Assuntos
Variação Genética , Espasmos Infantis/genética , Proteínas Adaptadoras de Transporte Vesicular/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , DNA (Citosina-5-)-Metiltransferases/genética , Epilepsias Mioclônicas/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Lactente , Japão , Síndrome de Lennox Gastaut/genética , Modelos Logísticos , Mutação , Neurofibromina 1/genética , Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , Canais de Cátion TRPM/genética , Sequenciamento Completo do Exoma
3.
Am J Med Genet A ; 179(3): 338-340, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30569574

RESUMO

SOFT syndrome (MIM614813) is an extremely rare primordial dwarfism caused by biallelic mutations in the POC1A gene. It is characterized by prenatal short stature, onychodysplasia, facial dysmorphism, hypotrichosis, and variable skeletal abnormalities including hypoplastic pelvis and sacrum, small hands, and cone-shaped epiphyses, as well as delayed bone age. To the best of our knowledge, only eight POC1A mutations have been reported in humans to date. We report a 7-year-old Chilean girl with SOFT syndrome arising from a novel POC1A mutation c. 649C>T, p.Arg217Trp. Although her clinical features were largely compatible with SOFT syndrome, hand X-ray examinations at 3.5 and 6 years unexpectedly showed normal bone age. Automated bone age determination was performed using image analysis software, BoneXpert. This case highlights the importance of the accumulation of patients with POC1A mutations to further elucidate the detailed clinical features of SOFT syndrome.

4.
BMC Nephrol ; 19(1): 365, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30558570

RESUMO

BACKGROUND: Bordetella pertussis infection is a known trigger of atypical hemolytic uremic syndrome (HUS). For patients suspected of having atypical HUS, prompt plasma exchange/infusion (PE/PI) or eculizumab (ECZ) treatment is recommended. CASE PRESENTATION: We report a 1-month-old female infant who was admitted with a severe cough and a B. pertussis-positive sputum culture. She was born at 38 weeks gestation and did not have a family history of renal diseases. Hemophagocytic syndrome was suspected and she was transferred to our hospital 17 days after her initial admission. One day later, she developed acute kidney injury and was diagnosed with HUS triggered by B. pertussis infection. Her plasma complement levels were low and her kidney function continued to worsen over the next few days. However, prior to starting ECZ treatment, her kidney function improved spontaneously; she did not receive PE/PI or ECZ. She was discharged 46 days after her initial hospitalization, without complications. A genetic workup revealed no mutations in CFH, CFI, CFB, C3, MCP, THBD, or DGKE. CONCLUSIONS: This case demonstrates that B. pertussis infection-related HUS may resolve spontaneously. The decision to treat during the acute phase is challenging because B. pertussis often affects infants suspected of having atypical HUS. However, ECZ may not be the first treatment option for patients with B. pertussis infection-related HUS unless they show an indicated genetic abnormality; if ECZ is used, early discontinuation should be considered.

5.
Am J Hum Genet ; 103(2): 305-316, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30057029

RESUMO

Next-generation sequencing combined with international data sharing has enormously facilitated identification of new disease-associated genes and mutations. This is particularly true for genetically extremely heterogeneous entities such as neurodevelopmental disorders (NDDs). Through exome sequencing and world-wide collaborations, we identified and assembled 20 individuals with de novo variants in FBXO11. They present with mild to severe developmental delay associated with a range of features including short (4/20) or tall (2/20) stature, obesity (5/20), microcephaly (4/19) or macrocephaly (2/19), behavioral problems (17/20), seizures (5/20), cleft lip or palate or bifid uvula (3/20), and minor skeletal anomalies. FBXO11 encodes a member of the F-Box protein family, constituting a subunit of an E3-ubiquitin ligase complex. This complex is involved in ubiquitination and proteasomal degradation and thus in controlling critical biological processes by regulating protein turnover. The identified de novo aberrations comprise two large deletions, ten likely gene disrupting variants, and eight missense variants distributed throughout FBXO11. Structural modeling for missense variants located in the CASH or the Zinc-finger UBR domains suggests destabilization of the protein. This, in combination with the observed spectrum and localization of identified variants and the lack of apparent genotype-phenotype correlations, is compatible with loss of function or haploinsufficiency as an underlying mechanism. We implicate de novo missense and likely gene disrupting variants in FBXO11 in a neurodevelopmental disorder with variable intellectual disability and various other features.

6.
Brain Dev ; 40(7): 566-569, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29678278

RESUMO

BACKGROUND: Coffin-Lowry syndrome is a rare X-linked disease, caused by loss-of-function mutations in the RPS6KA3 gene. Patients exhibit severe intellectual disability with characteristic dysmorphism. As there are no specific laboratory findings to support the diagnosis of Coffin-Lowry syndrome, it may be difficult to diagnose-especially in young children, where the characteristic craniofacial features are less discernible. CASE: Here we report on a 2-year-old boy with Coffin-Lowry syndrome with a novel missense mutation in the RPS6KA3 gene. On magnetic resonance imaging, his brain exhibited periventricular signal abnormalities with multiple small cystic lesions. These findings may aid in diagnosis of Coffin-Lowry syndrome.


Assuntos
Encéfalo/diagnóstico por imagem , Síndrome de Coffin-Lowry/diagnóstico , Síndrome de Coffin-Lowry/genética , Mutação de Sentido Incorreto , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Pré-Escolar , Síndrome de Coffin-Lowry/patologia , Diagnóstico Diferencial , Face/anormalidades , Humanos , Imagem por Ressonância Magnética , Masculino , Fenótipo
7.
Nephrology (Carlton) ; 23(6): 592-596, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28976051

RESUMO

Children with systemic lupus erythematosus (SLE) generally undergo a pretreatment kidney biopsy. However, some of these patients, especially those with antiphospholipid syndrome (APS), may experience serious coagulopathic complications. We report herein two cases of paediatric SLE with APS in which, despite normal blood test results, the disparate coagulopathic complications of haemorrhage and embolism developed following a kidney biopsy. Case 1 was, an 8-year-old male in whom, primary APS was initially diagnosed. Fourteen months later SLE was diagnosed. Based on a percutaneous kidney biopsy, International Society of Nephrology and the Renal Pathology Society (ISN/RPS) class III-A lupus nephritis was histologically diagnosed. On post-biopsy Day 9, a giant haematoma in the fascia of the left kidney developed and was accompanied by changes in the vital signs. Case 2, a 13-year-old male, initially received the diagnosis of SLE with APS and underwent two courses of pulse methylprednisolone therapy. His coagulation abnormalities improved, and a percutaneous needle kidney biopsy was performed, leading to the histological diagnosis of ISN/RPS class III-A lupus nephritis. Furthermore, thrombotic microangiopathy was also detected in the renal histopathology. On post biopsy Day 6, the patient experienced right leg pain. A contrast CT and lower extremity ultrasonography detected a massive deep vein thrombosis and partial left pulmonary artery thrombosis. A kidney biopsy in children with SLE and APS can cause lethal coagulopathic complications, and the risks to such patients should be weighed carefully before the procedure is performed.


Assuntos
Síndrome Antifosfolipídica/complicações , Arteriopatias Oclusivas/etiologia , Biópsia/efeitos adversos , Hematoma/etiologia , Rim/patologia , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/etiologia , Trombose Venosa/etiologia , Adolescente , Idade de Início , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/tratamento farmacológico , Coagulação Sanguínea , Criança , Glucocorticoides/uso terapêutico , Hematoma/sangue , Hematoma/diagnóstico , Hematoma/tratamento farmacológico , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/patologia , Masculino , Fatores de Risco , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler em Cores , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/tratamento farmacológico
9.
Nephrology (Carlton) ; 22(7): 566-571, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28621010

RESUMO

WDR19 has been reported as a causative gene of nephronophthisis-related ciliopathies. Patients with WDR19 mutations can show various extrarenal manifestations such as skeletal disorders, Caroli disease, and retinal dystrophy, and typically display nephronophthisis as a renal phenotype. However, there is limited information on the renal phenotypes of patients with WDR19 mutations. We report two Japanese infants with Sensenbrenner syndrome caused by WDR19 mutations who demonstrated different features in renal ultrasound and histopathological results, despite several common extrarenal manifestations. Patient 1 had normal sized and hyperechogenic kidneys with several small cysts and histopathological findings compatible with infantile nephronophthisis. Renal ultrasound of Patient 2 showed enlarged kidneys with diffuse microcysts resembling those of autosomal recessive polycystic kidney disease. Her renal histopathology revealed dysplastic kidney with diffuse glomerular cysts. Genetic testing identified compound heterozygous mutations in WDR19 in both patients (Patient 1: c.953delA, c.3533G > A, Patient 2: c.2645 + 1G > T, c.3533G > A). Our patients suggest that WDR19 mutations can cause dysplastic kidney in addition to nephronophthisis pathologically. In addition, differences in pathology of the kidneys from WDR19 mutations may result in heterogeneous features in renal ultrasound findings. Renal phenotypes from WDR19 mutations may thus be more diverse than previously reported. Extrarenal manifestations and genetic testing can therefore help to diagnosis this disease more precisely.


Assuntos
Osso e Ossos/anormalidades , Craniossinostoses/genética , Displasia Ectodérmica/genética , Doenças Renais Císticas/genética , Rim/anormalidades , Mutação , Rim Policístico Autossômico Recessivo/genética , Proteínas/genética , Biópsia , Pré-Escolar , Craniossinostoses/diagnóstico , Craniossinostoses/terapia , Análise Mutacional de DNA , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/terapia , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Lactente , Rim/diagnóstico por imagem , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/terapia , Imagem por Ressonância Magnética , Fenótipo , Rim Policístico Autossômico Recessivo/diagnóstico , Rim Policístico Autossômico Recessivo/terapia , Ultrassonografia
10.
Pediatr Int ; 58(6): 537-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27322865

RESUMO

The incidence of ampicillin (ABPC)-resistant Escherichia coli (E. coli) infection in very low-birthweight infants has been increasing. The rate of ABPC/sulbactam (ABPC/SBT)-resistant E. coli in this population, however, is currently unknown. We encountered two cases of severe infection due to resistant E. coli and retrospectively studied the prevalence of ABPC- and ABPC/SBT-resistant E. coli in regular surveillance cultures obtained from all neonatal intensive care unit (NICU) patients between 2000 and 2013. The overall prevalence of ABPC-resistant E. coli was 39% (47/120), accounting for 63% of cases (32/51) between 2007 and 2013, compared with 22% (15/69) between 2000 and 2006. The prevalence of ABPC/SBT resistance was 17% (20/120), which was similar in both periods (16%, 8/51 vs 17%, 12/69). According to these results, not only ABPC, but also ABPC/SBT-resistant E. coli must be considered in the NICU.


Assuntos
Ampicilina/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Escherichia coli/epidemiologia , Escherichia coli/isolamento & purificação , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Sulbactam/uso terapêutico , Fatores Etários , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Incidência , Recém-Nascido , Japão/epidemiologia , Masculino
11.
Clin Exp Nephrol ; 20(2): 265-72, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26156042

RESUMO

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a severe life-threatening disease with frequent progression to end-stage renal disease (ESRD). Eculizumab, a humanized anti-C5 monoclonal antibody targeting the activated complement pathway, has recently been introduced as a novel therapy against aHUS. We, therefore, investigated the efficacy and safety of eculizumab in Japanese pediatric patients. METHODS: We retrospectively analyzed clinical course and laboratory data of the first ten children with aHUS treated with eculizumab nationwide. RESULTS: Seven patients were resistant to plasma therapy and three were dependent on it. Causative gene mutations were found in five patients. Two patients had anti-complement factor H autoantibody. Three patients had a family history of thrombotic microangiopathy (TMA). After initiation of eculizumab, all patients immediately achieved hematological remission and could successfully discontinue plasma therapy. The median periods to normalization of platelet count, lactate dehydrogenase levels and disappearance of schistocytes were 5.5, 17 and 12 days, respectively. Nine patients recovered their renal function and the median period to terminate renal replacement therapy (RRT) was 3 days. However, two patients progressed to ESRD and required chronic RRT at the last observation. No patients had a relapse of TMA under regular eculizumab therapy. No serious adverse events occurred during the follow-up period. CONCLUSIONS: Eculizumab is efficacious and well-tolerated therapy for children with aHUS. Although pathogenic mutations could not be detected in five patients, all patients showed immediate normalization of hematological abnormalities, strongly suggesting complement-related aHUS. This prompt hematological amelioration can become an indicator for therapeutic efficacy of eculizumab. However, appropriate indications and optimal duration of the treatment remain unclear.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
12.
PLoS One ; 10(9): e0136317, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26325687

RESUMO

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by central obesity, mental impairment, rod-cone dystrophy, polydactyly, hypogonadism in males, and renal abnormalities. The causative genes have been identified as BBS1-19. In Western countries, this disease is often reported, but remains undiagnosed in many patients until later in life, while only a few patients with no mutations identified have been reported in Japan. We thus conducted the first nationwide survey of BBS in Japan by sending questionnaires to 2,166 clinical departments with board-certified specialists and found 7 patients with clinically definite BBS. We performed exome analyses combined with analyses of mRNA and protein in these patients. We identified 2 novel mutations in the BBS5 gene (p.R89X and IVS7-27 T>G) in 2 sibling patients. The latter mutation that resided far from the authentic splicing site was associated with skipping of exon 8. We also found 3 previously reported mutations in the BBS2 (p.R413X and p.R480X) and BBS7 (p.C243Y) genes in 2 patients. To our knowledge, a nationwide survey of BBS has not been reported in any other country. In addition, this is the first study to identify genetic alterations in Japanese patients with BBS. Our results indicate that BBS in Japan is genetically heterogeneous and at least partly shares genetic features with BBS in other countries.


Assuntos
Síndrome de Bardet-Biedl/epidemiologia , Adolescente , Síndrome de Bardet-Biedl/genética , Criança , Pré-Escolar , Exoma/genética , Feminino , Humanos , Japão/epidemiologia , Masculino , Mutação/genética , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas/genética , Inquéritos e Questionários , Adulto Jovem
13.
Eur J Pediatr ; 174(4): 551-5, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25194957

RESUMO

UNLABELLED: Staphylococcal scalded skin syndrome (SSSS) demonstrates dermal symptoms due to exfoliative toxin (ET) A or ETB produced by Staphylococcus aureus. We examined the association between anti-ETA antibodies and SSSS onset in neonates. Three preterm infants carried an ETA-producing strain of S. aureus, manifesting as either SSSS or bullous impetigo; a full-term infant carrying the same strain was asymptomatic. The infants (n=106) were categorized into three groups according to their gestational age (GA) as follows: <30 weeks, 30-37 weeks, and >37 weeks. The measured levels of anti-ETA antibody in the three infants displaying SSSS were low before the onset of dermal symptoms; only the asymptomatic full-term infant displayed a high antibody level. Anti-ETA antibody levels in the preterm group with a GA of <30 weeks were statistically lower than those in the term infant group; the prevalences of anti-ETA antibodies above a cutoff value in the three groups of neonates were 55 % (18/33) among preterm infants with a GA <30 weeks, 73 % (25/34) among those with a GA of 30-37 weeks, and 90 % (35/39) among infants with a GA >37 weeks. CONCLUSION: The presence of anti-ETA antibodies below a particular cutoff level might be associated with SSSS onset in preterm infants.


Assuntos
Exfoliatinas/imunologia , Infecções Estafilocócicas/diagnóstico , Síndrome da Pele Escaldada Estafilocócica/diagnóstico , Staphylococcus aureus/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Infecções Estafilocócicas/imunologia , Síndrome da Pele Escaldada Estafilocócica/imunologia
14.
Nephrol Dial Transplant ; 30(1): 91-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25085238

RESUMO

BACKGROUND: Agranulocytosis has been reported as a delayed-onset complication of rituximab treatment. However, the exact incidence and risk factors of this complication in patients with nephrotic syndrome remain unknown. METHODS: Records of 213 rituximab treatments for 114 patients with refractory nephrotic syndrome between February 2006 and April 2013 were reviewed to identify episodes of agranulocytosis (defined as an absolute neutrophil count of <500 mm(3)). RESULTS: Eleven episodes of agranulocytosis were detected in 11 patients. Median time of onset of agranulocytosis was 66 days (range, 54-161 days) after rituximab treatment. Nine patients experienced acute infections and received antibiotics. All but one patient received granulocyte colony-stimulating factor. Agranulocytosis resolved in all cases within a median of 3 days. The incidence of agranulocytosis was 9.6% in total patients and 5.2% in all treatments. Median age of the 11 patients who developed agranulocytosis was 6.4 years at the first rituximab treatment, significantly younger than the median age of the 103 patients who did not (median, 12.5 years; P = 0.0009). Five patients received re-treatment with rituximab. No recurrence of agranulocytosis was observed in any patient. CONCLUSIONS: It is important to pay extra attention to this clinically serious delayed-onset complication as it may be accompanied by life-threatening infections such as sepsis. Further clinical studies are needed to clarify its pathogenesis.


Assuntos
Agranulocitose/induzido quimicamente , Anticorpos Monoclonais Murinos/efeitos adversos , Antineoplásicos/efeitos adversos , Síndrome Nefrótica/tratamento farmacológico , Adolescente , Agranulocitose/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Fator Estimulador de Colônias de Granulócitos , Humanos , Lactente , Masculino , Recidiva , Literatura de Revisão como Assunto , Fatores de Risco , Rituximab
15.
CEN Case Rep ; 3(2): 132-138, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28509186

RESUMO

Dent disease is an inherited tubulopathy caused by a mutation in the CLCN5 chloride channel gene. In cases of Dent disease in Japan (Japanese Dent, J-Dent), renal function is generally preserved and rarely progresses to advanced kidney dysfunction. However, the long-term prognosis of J-Dent remains unknown. We report the case of a 32-year-old man with J-Dent who developed advanced kidney dysfunction. Since the age of 3 years, he persistently exhibited proteinuria, and examination of a kidney biopsy specimen indicated focal segmental glomerulosclerosis (FSGS)-like lesions. Repeated corticosteroid treatments were found to be ineffective. After the age of 18 years, the patient was lost to follow-up and treatment was discontinued. The patient presented to our hospital again at the age of 32 years with advanced kidney dysfunction with low-molecular-weight proteinuria (LMWP), along with proximal tubular dysfunction and nephrocalcinosis. The patient's 5-year-old nephew was also found to have LMWP from the age of 7 months. Therefore, Dent disease was suspected and genetic testing in the patient and his nephew revealed a CLCN5 mutation. Our case report suggests that J-Dent may cause advanced kidney dysfunction in adulthood, and, therefore, close collaboration between pediatricians and nephrologists is essential for the early identification of this complication. When male patients exhibit chronic kidney disease (CKD) of unknown etiology along with proximal tubular dysfunction and nephrocalcinosis, Dent disease should be considered. Investigations of undiagnosed adult J-Dent cases and further research on the natural history of J-Dent will help us better understand its clinical characteristics, prognosis, and effective treatment options.

16.
Brain Dev ; 36(8): 721-4, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24290075

RESUMO

Bardet-Biedl syndrome (BBS) is a rare heterogeneous autosomal recessive disorder characterized by rod-cone dystrophy, postaxial polydactyly, truncal obesity, hypogonadism, learning disability, and renal anomaly that are caused by ciliary dysfunction. 16 genes have been associated with the BBS phenotype. Although recent pathophysiological studies using animal models have shown that ciliary dysfunction may induce hydrocephalus, there have been no reports of BBS with intracranial hypertension. We here describe a 9-year-old Japanese girl who was diagnosed as having BBS and later received renal transplantation due to chronic renal failure. She also exhibited intracranial hypertension, including papilledema and increased intrathecal pressure (260-300 mmH2O), but her brain magnetic resonance imaging was normal. No genetic abnormalities were detected by DNA chip analysis or exome sequencing. Her papilledema improved following administration of acetazolamide. This is the first report of a case of BBS complicated with intracranial hypertension and its treatment.


Assuntos
Síndrome de Bardet-Biedl/complicações , Síndrome de Bardet-Biedl/diagnóstico , Hipertensão Intracraniana/complicações , Síndrome de Bardet-Biedl/metabolismo , Criança , Feminino , Humanos , Japão , Papiledema/complicações
17.
Early Hum Dev ; 89(10): 821-3, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23916057

RESUMO

Patent ductus arteriosus (PDA) is common in premature infants. In very low birth weight infants (VLBWI), PDA requires surgical therapy in many cases. It is unclear to know at-risk infants showing cardio-dysfunction after PDA surgery. The purpose of this study was to identify at-risk infants showing cardio-dysfunction after surgery for patent ductus arteriosus (PDA). We examined the relationship between left ventricular (LV) performance before and after PDA ligation in a retrospective observational cohort study. We studied 64 preterm neonates with symptomatic PDA before and after surgical ligation. Echocardiographic examinations were performed pre- and postoperatively. M-mode measurements included left ventricular internal dimension in end-diastole (LVIDd) and LV fractional shortening (FS). All cases showed decreased LVFS after PDA closure. Most cases (49/64, 77%) showed postoperative FS decreased to below normal (<28%). Preoperative relative LVIDd was significantly larger in abnormal FS infants (137 ± 18%) than in normal FS infants (118 ± 11%; p<0.01). A cut-off value of preoperative relative LVIDd (absolute LVIDd/normal value) for predicting postoperative cardio-dysfunction was 127.4% (sensitivity, 0.735; specificity, 0.933; area under curve, 0.817). Determination of preoperative LVIDd might facilitate earlier identification of infants needing early PDA surgery and postoperative intensive care.


Assuntos
Permeabilidade do Canal Arterial/diagnóstico , Permeabilidade do Canal Arterial/cirurgia , Recém-Nascido de muito Baixo Peso/fisiologia , Estudos de Coortes , Idade Gestacional , Ventrículos do Coração , Humanos , Indometacina/administração & dosagem , Recém-Nascido , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/cirurgia , Terapia Intensiva Neonatal , Cuidados Pós-Operatórios , Estudos Retrospectivos , Resultado do Tratamento , Função Ventricular Esquerda
19.
Pediatr Crit Care Med ; 13(1): 60-5, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21460760

RESUMO

OBJECTIVE: To investigate postnatal changes in the direction of blood flow through the ductus arteriosus in neonates with meconium-stained amniotic fluid, we measured preductal and postductal oxygen saturation in normal neonates, neonates with meconium-stained amniotic fluid, and a neonate with persistent pulmonary hypertension of the newborn. DESIGN: Prospective, observational case series report. SETTING: A single, tertiary neonatal intensive care unit. PATIENTS: Twelve normal neonates, seven neonates with meconium-stained amniotic fluid, and a neonate with persistent pulmonary hypertension of the newborn. INTERVENTIONS: SpO2 is simultaneously monitored in the right upper and lower limbs after birth. MEASUREMENTS AND MAIN RESULTS: Compared with normal neonates, three neonates with meconium-stained amniotic fluid required longer than +2 SD of the mean time for the postductal SpO2 to reach 90% and/or 95%. In a neonate with meconium-stained amniotic fluid, intense crying triggered frequent decreases to <70% in the postductal SpO2 from 25 mins after birth, while the preductal SpO2 remained at 95% or above. When the other newborn with meconium-stained amniotic fluid was held in the father's arms after 98 mins, the postductal SpO2 decreased rapidly to <80%, while the preductal SpO2 remained at 95%. Thus, 5% or greater difference between the preductal and postductal SpO2 was observed from 25 mins after birth until 120 mins in all neonates with meconium-stained amniotic fluid, whereas the difference disappeared after 25 mins in 12 normal neonates. In a neonate with persistent pulmonary hypertension of the newborn who required vigorous resuscitation, 5% or greater difference between the preductal and postductal SpO2 levels was observed until 6 hrs after birth. CONCLUSIONS: Right-to-left shunting in the ductus arteriosus may be induced readily by intense crying and rapid postural change in infants with meconium-stained amniotic fluid. It is important to monitor SpO2 at both pre- and postductal regions until 120 mins after birth in neonates with meconium-stained amniotic fluid and to subject these infants to minimal manipulations.


Assuntos
Choro/fisiologia , Canal Arterial/fisiologia , Hipertensão Pulmonar/diagnóstico , Síndrome de Aspiração de Mecônio/diagnóstico , Oxigênio/sangue , Postura/fisiologia , Líquido Amniótico , Velocidade do Fluxo Sanguíneo , Gasometria , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Estudos Prospectivos , Valores de Referência , Fluxo Sanguíneo Regional
20.
Int J Hematol ; 80(3): 287-90, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15540906

RESUMO

Here we report the first successful unrelated cord blood transplantation (CBT) using reduced-intensity conditioning for the 'treatment of congenital neutropenia in a 6-month-old infant with complications of severe pneumonia probably due to Staphylococcus aureus infection. Because the patient showed no response to treatment with granulocyte colony-stimulating factor and had a cytogenetic aberration, unrelated CBT with an HLA-DRB1 genotypic mismatch was performed. The number of infused cells was 15 x 10(7)/kg. The preparative regimen was fludarabine, cyclophosphamide, and 6 Gy of total body irradiation. Teicoplanin was administered for bacterial pneumonia. Neutrophil engraftment was achieved on day 41 and was followed by clinical improvement. The patient gradually caught up on growth and development after the CBT. Unrelated CBT using a reduced-intensity conditioning regimen may be an effective treatment for congenital neutropenia.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Neutropenia/terapia , Pneumonia/etiologia , Condicionamento Pré-Transplante/métodos , Estatura , Sobrevivência de Enxerto/imunologia , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Hematopoese , Histocompatibilidade , Humanos , Lactente , Masculino , Neutropenia/complicações , Neutropenia/congênito , Pneumonia/tratamento farmacológico , Indução de Remissão/métodos , Doadores de Tecidos , Quimeras de Transplante
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