Perinatal lethal Gaucher disease: a distinct phenotype along the neuronopathic continuum

Gaucher disease, the inherited deficiency of glucocerebrosidase, is characterized by significant genetic and phenotypic heterogeneity. At the extreme end of the phenotypic continuum is the perinatal lethal variant, typically presenting in utero or during the neonatal period as hydrops and/orcongenital ichthyosis, with severe and progressive neurological involvement. Insights from the null-allele Gaucher mouse model contributed to the identification of this distinct phenotype, which has unique epidermal involvement. While multiple mutations are encountered, many affected infants are homozygous for recombinant alleles. The diagnosis is often missed due to the early lethality and the failure to recognize the association between lysosomal disorders and hydrops fetalis. The incidence of severe perinatal Gaucher disease may prove more common than currently appreciated with greater physician awareness of the disorder.     

Hemophagocytic lymphohistiocytosis with Munc13-4 mutation: a cause of recurrent fatal hydrops fetalis

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disorder of immune regulation that leads to a hyperinflammatory syndrome responsible for fever, hepatosplenomegaly, cytopenia, and coagulopathy. Although presentation usually occurs in early infancy, antenatal presentation is extremely rare. To our knowledge, we are first to report genetically confirmed FHL in 2 consecutive siblings who presented with hydrops fetalis that led to spontaneous intrauterine death at 38 and 30 weeks of gestation. Because the diagnosis of FHL has important implications for genetic counseling, we suggest that FHL be considered in the differential diagnosis of nonimmune hydrops fetalis.     

Severe hydrops fetalis due to congenital supraventricular tachycardia

Intrauterine supraventricular tachycardia is one of the main causes of non-immunological intrauterine hydrops fetalis. Without early diagnosis and treatment it may terminate in fetal death or delivery of a baby with severe hydrops and extrene heart failure.With the improvement in non-invasive imaging techniques in prenatal medicine, this condition can be diagnosed early and treated successfully. A case is described of such a newborn diagnosed in utero and treated before and after delivery, and the different therapeutic approaches to congenital supraventricular tachycardia are discussed.     

Diamond-Blackfan syndrome: an unusual cause of hydrops fetalis

An unusual case of Diamond-Blackfan syndrome whose initial presentation was hydrops fetalis is presented. Diamond-Blackfan syndrome and the pathophysiology of hydrops fetalis in severely anemic infants are briefly reviewed.     

A Case of Hydrops Foetalis due to Foeto-Maternal Haemorrhage

Early exchange transfusion and ventilatory support were used in the successful management of an hydropic infant where anaemia was due to massive, occult foetomaternal haemorrhage.
The occurrence of foeto-maternal haemorrhage with resultant non-haemolytic neonatal anaemia has been recognised for several decades (Wiener and Brooklyn, 1948; Chown, 1954). However, there are only two reported cases where foeto-maternal haemorrhage resulted in hydrops foetalis (Weiner, 1958; Weisert and Marstrander, 1960). Despite exchange transfusion, both infants died on the first day of life.
We report the case of a successfully treated infant with hydrops foetalis due to massive, occult foeto-maternal haemorrhage, to illustrate the importance of early recognition and appropriate management.     

Nonimmunologic hydrops fetalis--a review of 31 cases

Non-immunologic hydrops fetalis-a review of 31 cases: 31 Patients with non-immunologic hydrops fetalis (NIHF) seen between 1984 and 1987 are described. 13 infants survived. The infants with major congenital malformations and connatal infections died. In 8 of the patients who died a cause for NIHF could not be identified. 10 of the survivors presented chylous ascites and/or chylothorax without major congenital anomalies. 2 infants had fetal tachyarrhythmia and 1 patient showed severe anemia due to fetomaternal hemorrhage.     

CONGENITAL PARVOVIRUS INFECTION

Congenital parvovirus infection was diagnosed in two liveborn premature infants born at 24 and 35 weeks of gestational age. The illnesses were associated with placentomegaly, petechial rash, edema, hepatomegaly, anemia and thrombocytopenia, respiratory insufficiency, and death at 5 and 6 days of age. The syndromes exhibited by these cases shared common but nonspecific features with other life-threatening congenital infections. Serological studies in one case supported the diagnosis of parvoviral infection. Postmortem examination of both revealed nuclear inclusions in erythroid precursor cells characteristic of parvovirus infection. Use of the polymerase chain reaction confirmed the presence of parvovirus DNA in one of the cases. Intrauterine parvovirus B19 infection is most commonly associated with hydrops fetalis, "transient" hydrops, or a favorable outcome in infants found to be viremic after birth. These and previously reported examples of congenital B19 disease exemplify an exceptional form of human parvovirus infection.     

Segmental bowel-wall thickening on abdominal ultrasonography: an additional diagnostic sign in Kawasaki disease

Abdominal complaints are a frequent early feature of Kawasaki disease, an acute systemic febrile vasculitis of childhood. The only well known correlating morphological finding on abdominal US is gallbladder hydrops. We report two boys with Kawasaki disease who showed segmental thickening of the small-bowel wall on abdominal US. These changes are thought to result from bowel-wall oedema due to vasculitis of the supplying vessels. We conclude that in an acutely ill febrile child with the finding of segmental bowel-wall thickening on abdominal US, Kawasaki disease should be considered in the differential diagnosis. The search for gallbladder hydrops and segmental bowel-wall thickening on abdominal US may serve as an important diagnostic tool in Kawasaki disease, supporting early recognition and prompt treatment.     

Congenital chylothorax with hydrops: postnatal care and outcome following antenatal diagnosis

We consecutively managed 25 cases of fetal chylothorax with hydrops (pleuroamniotic shunting in 20/25 cases). Three of the 16 liveborn infants died before day 5 from malformations (n = 1) or complications of antenatal origin (n = 2). Eleven of the 13 survivors were treated in our unit. Four infants whose chylothorax had resolved before birth following antenatal shunting were delivered at term, and had no respiratory disease. Seven infants, whose chylothorax persisted, were delivered prematurely and required intensive respiratory care (with mechanical ventilation for a median duration of 34 days). The 11 infants were maintained on total parenteral nutrition for a median duration of 31 days. They were discharged home after complete clinical recovery at a median age of 64 days. Antenatal pleuroamniotic shunting may improve the prognosis of congenital chylothorax with hydrops. Chylothorax persisting at birth resolves progressively with medical management. Congenital chylothorax, critical care, non-immunologic fetal hydrops, pleuroamnotic shunting, preterm newborn     

The diagnosis and treatment of the nonimmune hydrops fetalis

Fetal hydrops is associated with two distinct pathophysiologic situations. The isoimmune hydrops fetalis is a well understood disorder, and as the result of medical advances and prophylactic therapy its frequency is diminishing. The nonimmune hydrops fetalis is a poorly understood disease with a bad prognosis. The two disorders can be differentiated with the indirect Coombs test. In both cases the ultrasound examination plays an important role in the diagnosis, prognosis and management. Examination of the fetal blood sample gives recently a possibility to approach the disease. In NIHF the examination of fetal blood sample would give a relatively quick and effective diagnosis but its value for the treatment is limited. Although with the present technology it is impossible to diagnose all cases of NIHF, the early recognizing, the careful and step by step investigation, the active perinatologic management mostly can show the etiology and can help the perinatal team at the treatment of the disease.     

Meconium peritonitis and parvovirus B19 infection associated with hydrops fetalis

Two preterm infants with non-immune hydrops fetalis associated with meconium peritonitis are reported. The first presented with a cystic abdominal mass and the second had positive parvovirus B19 serology. The association of meconium peritonitis with hydrops fetalis was through different mechanisms in each patient.     

Pulmonary vasculature changes associated with idiopathic closure of the ductus arteriosus and hydrops fetalis

Summary Antenatal closure of the ductus arteriosus has been considered as a potential risk factor for the development of hydrops fetalis and persistent fetal circulation of the newborn. We present an infant with antenatal ductal closure who had not received prenatal prostaglandin synthetase inhibitors. The pulmonary vascular morphological findings are described and compared to three additional infants in whom the ductus arteriosus was known to be patent; one with neonatal sepsis and two others with hydrops fetalis.The infants with fetal hydrops, regardless of etiology, had increased muscularization of the acinar pulmonary arteries. In addition, the infant with antenatal closure of the ductus arteriosus also had both a significant decrease in preacinar arterial external diameter and an increase in medial wall thickness. Antenatal closure of the ductus arteriosus appears to enhancein utero pulmonary blood flow and this may be the cause of pulmonary vascular remodeling.     

Fatal course of ABO hemolytic disease associated with hydrops in a twin pregnancy

Hydrops fetalis associated with ABO incompatibility is an extremely rare condition. We report twin infants both afflicted with significant ABO hemolytic disease but showing different degrees of clinical severity, in which fatal hydrops developed in one of the twins. Hemolysis due to ABO incompatibility is usually difficult to diagnose. All causes of non-immune hydrops should be ruled out in order to identify hydrops due to ABO incompatibility.     

Nonimmunologic hydrops fetalis: a clinicopathological study of 50 autopsy cases

Fifty cases of nonimmunologic hydrops fetalis found in Japanese infants are reported. Nonimmunologic hydrops fetalis is associated with various pathological conditions, twin transfusion syndrome including acardiac monsters, fetal heart diseases, congenital cystic adenomatoid malformation, pulmonary sequestration, pulmonary lymphangiectasia, intrauterine infections such as cytomegalovirus infection and neonatal hepatitis, congenital neuroblastoma, Kasabach-Merritt syndrome, cystic hygroma, and chromosomal aberrations. The mechanism of hydrops fetalis found in these conditions is discussed from various viewpoints. Despite a careful examination, no causative conditions were found in 14 cases. The placenta showed a proliferation of Hofbauer cells that were strongly positive for immunoreactive alpha 1-antichymotrypsin and there were other common findings such as edema of terminal villi and fibrin thrombi.     

Free sialic acid storage disorders with fetal hydrops in a neonate北大核心CSCD

患儿,男,生后3 h,因产前诊断胎儿水肿、出生窒息复苏后3 h入院。患儿母亲孕5个月产检提示胎儿有大量腹水,患儿生后表现为全身皮肤水肿、大量腹水、面容粗糙、肝大。基因检测提示SLC17A5基因杂合变异,尿游离唾液酸显著升高,胎盘病理回报绒毛间质细胞、霍夫鲍尔细胞、细胞滋养层细胞和合体滋养层细胞广泛空泡化,该患儿最终诊断为唾液酸贮积症。该例患儿为国内首次报道以胎儿水肿为首发症状的唾液酸贮积症新生儿。对非免疫性胎儿水肿病例需考虑唾液酸贮积症可能,胎盘病理、尿游离唾液酸等检查有助于早期诊断和指导临床决策。     

Characteristics of Kawasaki disease in infants younger than six months of age

BACKGROUND: Kawasaki disease is the leading cause of acquired heart disease in childhood. However, there are only a few reports in infants younger than 6 months. The objective of this study is to investigate the clinical and laboratory characteristics of Kawasaki disease in infants younger than 6 months. METHODS: From 1994 to 2003, 120 patients with Kawasaki disease diagnosed at our institution were included. Group 1 consisted of 20 (17%) patients younger than 6 months, and group 2 consisted of 100 (83%) patients older than 6 months. Clinical manifestations, laboratory results, echocardiographic findings, treatment and outcome were compared between these 2 groups. RESULTS: Clinical manifestations (hydrops of gallbladder: 0% versus 16%, P < 0.001) and laboratory results (white blood cell count 21,740 +/- 11,706 versus 11,830 +/- 4390/mm3, P < 0.001; hemoglobin 9.98 +/- 1.25 versus 10.8 +/- 1.37 g/dL, P = 0.015; platelet 483 +/- 393 versus 355 +/- 138 x 1000/mm3, P = 0.011; triglyceride 138 +/- 77.5 versus 107 +/- 17 mg/dL, P < 0.001) were different between patients with Kawasaki disease younger and older than 6 months, respectively. Younger infants were more likely to have incomplete presentation (35% versus 12%, P = 0.025), coronary involvement (65% versus 19%, P < 0.001), late intravenous immunoglobulin treatment and relatively poor outcome. CONCLUSIONS: Infants younger than 6 months with prolonged unexplained febrile illnesses should be suspected as having Kawasaki disease, despite the incomplete clinical presentation. Because early diagnosis and timely treatment are difficult in younger infants with Kawasaki disease because of delayed and incomplete clinical presentations, echocardiogram becomes an important implement for diagnosis. Early intravenous immunoglobulin treatment is required in view of the highest risk of coronary involvement in them.     

Successful pleurodesis with OK-432 in preterm infants with persistent pleural effusion

OK-432 (picibanil) is an inactivated preparation of Streptococcus pyogenes that causes pleurodesis by inducing a strong inflammatory response. Intrapleural instillation of OK-432 has recently been used to successfully treat neonatal and fetal chylothorax. Here we report a trial of intrapleural instillation of OK-432 in two preterm infants who were born with hydrops fetalis and massive bilateral pleural effusion. Both cases showed persistent pleural effusion, refractory to conservative treatment, up to postnatal days 26 and 46, respectively. An average of 80 to 140 mL of pleural fluid was drained daily. In case 1, the infant was treated with OK-432 during the fetal period at gestation 28 weeks and 4 days of gestation, but showed recurrence of pleural effusion and progressed into hydrops. Within two to three days after OK-432 injection, the amount of pleural fluid drainage was dramatically decreased and there was no reaccumulation. We did not observe any side effects related to OK-432 injection. We suggest that OK-432 should be considered as a therapeutic option in infants who have persistent pleural effusion for more than four weeks, with the expectation of the early removal of the chest tube and a good outcome.     

Histological structure of the thyroid gland in the newborn. With special reference to hypotrophy, hydrops fetalis and Cesarean section delivery.

Histological features of the thyroid gland in the newborns have been described under several circumstances; gestational age, length of survival, and under particular clinical status such as hypotrophy (intrauterine growth retardation), Cesarean section delivery and hydrops fetalis. Gestational age does not modify significantly the histological aspect of the thyroid, while birth process and adjustment to extrauterine life induce dramatic changes such as severe depletion of colloid for about 24 h, followed by a massive repletion after the first day of life. A few exceptions to this phenomenon are described. Thyroid glands of hypotrophic infants and of infants delivered by cesarean section exhibit colloid-filled vesicles already within the first day. Thyroid glands of hydrops fetalis have a reverse tendency. This phenomenon might be secondary to multiple exchange transfusions.     

Hydrops Fetalis and Neonatal Leukemia in Down Syndrome

Four newborn infants with Down syndrome and manifestations of neonatal leukemia are described. One of the four was stillborn, two died shortly after birth, and a fourth survived and all evidence of leukemia disappeared in the first month of life. Three of the four cases had hydrops fetalis, and a fourth was a macerated stillborn. Nine other similar reported cases are reviewed. We conclude that neonatal leukemia in Down syndrome is a form of leukemia that is usually transient, with spontaneous recovery, but may be fatal at or around the lime of birth with manifestations of hydrops fetalis, hepatosplenomegaly, and/or progressive liver disease.     

婴幼儿重症病毒性脑炎的临床分析

目的 探讨婴幼儿重症病毒性脑炎的临床特点,以期有助于早期诊断,指导治疗,改善预后.方法 对10例重症病毒性脑炎婴幼儿的临床资料进行回顾性分析.结果 婴幼儿重症病毒性脑炎以发热和神经症状起病为主,脑脊液常规检查及生化改变可不明显,脑电图和头颅影像学检查均有异常,6例留有各种神经后遗症.结论 婴幼儿重症病毒性脑炎的早期诊断应强调综合判断,脑脊液检查可以正常,脑电图有较高的辅助诊断价值.脑电图及影像学异常对预后判断有重要价值.