Hypoechoic liver in fetuses with trisomy 21.

The association between hypoechoic hepatomegaly in the third trimester and transient abnormal myelopoiesis (TAM) was reported previously in six fetuses with trisomy 21 (T21). We report a series of three cases of T21 in which hypoechoic liver (HL) was found in the second trimester but without evidence of TAM on both hematological and histological examination. We postulate that the hypo-echogenicity may be due to liver congestion secondary to hemodynamic disturbances seen in T21 fetuses. All three cases had negative first trimester Down syndrome screening and one case was detected solely because of the isolated finding of HL. HL per se may be associated with T21 and more positive cases are required to support this association.

An infant with congenital rubella syndrome in developing India.

Congenital rubella syndrome (CRS), caused by rubella virus infection during pregnancy, remains a public health concern in developing countries. Three to five per cent of all suspected CRS cases in India have been proven to be a rubella infection. Only about 45%-60% of pregnant women and infants in India receive the rubella vaccination. We present a case of a preterm female infant who tested positive for the rubella virus. The baby was born with low birth weight and, on examination, showed pallor and hepatosplenomegaly. She was detected to have an ostium secundum atrial septal defect (ASD) and a large patent ductus arteriosus (PDA) on echocardiography. On ophthalmic examination, she was diagnosed with bilateral cataract. She was treated with diuretics, and she underwent surgical correction for PDA. With this case we intend to present the literature, clinical manifestations and management of CRS. We will also focus on prevention, vaccination and disease burden in India..

Novel NLRC4 Mutation Causes a Syndrome of Perinatal Autoinflammation With Hemophagocytic Lymphohistiocytosis, Hepatosplenomegaly, Fetal Thrombotic Vasculopathy, and Congenital Anemia and Ascites.

Autoinflammatory diseases are caused by pathologic activation of the innate immune system. Primary hemophagocytic lymphohistiocytosis (HLH) is an aggressive syndrome of excessive immune activation caused by monogenic mutations resulting in cytotoxic cell defects and subsequent failure to eliminate activated macrophages. Secondary HLH is often diagnosed in cases without a known Mendelian inheritance. However, some cases of "secondary" HLH have been shown to harbor mutations with partial dysfunction of the cytotoxic system. Recently, macrophage intrinsic abnormalities caused by NLRC4 inflammasome mutations have been linked to autoinflammation and recurrent macrophage activation syndromes resembling a primary HLH. We report a case of a former 28-week preterm infant with congenital anemia, ascites, and a heavy edematous placenta with fetal thrombotic vasculopathy, who developed hepatosplenomegaly and unexplained systemic inflammation with laboratory features of HLH in the early postnatal course and died at 2 months of age. Postmortem examination confirmed the hepatosplenomegaly with marked sinusoidal hemophagocytosis, along with striking hemophagocytosis in the bone marrow and lymph nodes. There was extensive acute and chronic ischemic bowel disease with matted bowel loops, fibrous adhesions, and patchy necrotizing enterocolitis features. Whole exome sequencing analysis demonstrated a novel mosaic heterozygous NLRC4 512 C> T (p.Ser171Phe) de novo mutation predicated to cause a dominant, gain-of-function mutation resulting in a constitutively active protein. The assembly of NLRC4-containing inflammasomes via an induced self-propagation mechanism likely enables a perpetuating process of systemic macrophage activation, presumed to be initiated in utero in this patient.

Seroprevalence of Human Cytomegalovirus (HCMV) infection in pregnant women and outcomes of pregnancies with active infection.

OBJECTIVE: To determine the prevalence of cytomegalovirus in pregnant women and types of overt congenital infection in neonates. METHODS: This cross-sectional study was conducted at the Pakistan Institute of Medical Sciences and Federal Government Services Hospital in Islamabad, Pakistan, from March 2010 to June 2011, and comprised blood samples of pregnant women. Seroprevalence of human cytomegalovirus, immunoglobulin G and immunoglobulin M was determined by enzyme-linked immunosorbent assay while its deoxyribonucleic acid was detected by nested polymerase chain reaction.The congenital human cytomegalovirus infection was also identified in newborn babies from actively infected pregnant women. SPSS 18 was used for data analysis. RESULTS: Of the 409 pregnant women enrolled, 399(97.55%) were seropositive for cytomegalovirus immunoglobulinG and 52(12.71%) for immunoglobulinM, while cytomegalovirus deoxyribonucleic acid was detected in 82(20%). Of the cytomegalovirus immunoglobulinM-positive women, sera of 40(80%) had immunoglobulinG avidity >50%. The remaining 12(23%) sera had avidity assay value <50%. Among the 82(20%) infected pregnant women, 70(85.4%) were successfully followed up. Among them, the virus was isolated from 41(58.5%) newborns babies, of which 15(21%) were symptomatic while 26(47.2%) were asymptomatic. Of the former, 4(26.6%) had hepatosplenomegaly. CONCLUSIONS: Human cytomegalovirus infection in pregnant women was the main reason of congenital defects among neonates.

Accessory liver lobes: anatomical description and clinical implications.

Accessory liver lobes are a rare condition and appear to be due to excessive development of the liver. The presence of an accessory hepatic lobe is often diagnosed incidentally and sometimes revealed if it develops torsion, especially in pedunculated forms. In most cases, the accessory lobe is located below the liver, i.e., infrahepatic. Riedel's lobe is the best-known example of an accessory lobe, corresponding to hypertrophy of segments V and VI. While accessories lobes can simulate tumors, there have also been reports of hepatocellular tumor(s) that developed in these accessory lobes. Based on a review of the literature, this update focuses on accessory hepatic lobes.

Autoimmune lymphoproliferative syndrome with neonatal onset.

We describe 2 cases of autoimmune lymphoproliferative syndrome (ALPS), which is a rare disorder of auto-immunity, chronic persistent or recurrent lymphadenopathy, splenomegaly, hepatomegaly and hyper gamma globulinemia (1gG, 1gA). Both cases presented in neonatal period which is a rare age of presentation in this disease. A 20 days old female neonate presented with respiratory symptoms which rapidly progressed needing ventilatory support. There was hepatomegaly and no auscultatory findings in the chest. Serial CBCs (complete blood counts) showed persistent leucocytosis with predominant lymphocytosis. Her chest X-ray showed left sided consolidation which responded poorly to antibiotics. Her prompt clinical response to steroids raised the suspicion of autoimmunity and the diagnosis was established after a negative bone marrow examination for leukemia and a positive result for ALPS on flow cytometry. The second case presented with anemia, thrombocytopenia starting in neonatal period followed by persistent lymphadenopathy, hepatosplenomegaly and recurrent infections which responded poorly to antibiotics. Diagnosis was delayed due to low index of suspicion, and finally achieved with multiple radiological studies, histopathology and flow cytometry.

Elevated delta OD 450 due to transient abnormal myelopoiesis in a Down syndrome fetus with hepatosplenomegaly on ultrasound.

Transient abnormal myelopoiesis (TAM) is a relatively common finding in children with Down syndrome but has also been diagnosed prenatally, most often presenting with fetal hepatosplenomegaly. We report a case of TAM with hepatosplenomegaly found on ultrasound and associated with an increased amniotic fluid Δ OD 450 value. TAM is most commonly transient but can be associated with fatality and therefore should be considered in the differential diagnosis when fetal hepatosplenomegaly is found on ultrasound. Amniocentesis with chromosomal analysis and a Δ OD 450 may aid in diagnosing TAM and predicting the severity of the liver involvement.

Congenital lupus erythematosus presenting at birth with widespread erosions, pancytopenia, and subsequent hepatobiliary disease.

Neonatal lupus erythematosus is an uncommon disease caused by transplacental passage of maternal anti-Ro (SS-A), anti-LA (SS-B), or anti-U1RNP antibodies. Cutaneous findings of neonatal lupus are variable, but annular, erythematous plaques occurring within a few weeks of birth are most typical. Cutaneous lesions of congenital onset lupus erythematosus can differ from that of neonatal lupus erythematosus, presenting with atrophy or scarring, and less commonly, erosions. We report an unusual case of congenital lupus erythematosus presenting at birth with widespread erosions, pancytopenia, and subsequent hepatobiliary disease.

Autopsy case of the neonatal form of carnitine palmitoyltransferase-II deficiency triggered by a novel disease-causing mutation del1737C.

Carnitine palmitoyltransferase-II (CPT-II) deficiency is an autosomal recessive disease involving mitochondrial long-chain fatty acid oxidation that results in a distinct clinical phenotype. Reported herein is an autopsy case of the neonatal form of CPT-II deficiency in a 2-day-old Japanese boy who died due to a severe hepatocardiomuscular disease with an extremely early onset. Autopsy examination indicated massive pulmonary atelectasis with intra-alveolar hemorrhage, and the patient had marked cardiomegaly and hepatomegaly, both of which demonstrated the presence of abundant intracytoplasmic steatosis. Three years after the autopsy examination, CPT-II deficiency was suggested by acylcarnitine analysis of dried-blood on filter paper from the patient's younger sister at the age of 1. The younger sister also died due to sudden onset of cardiopulmonary arrest; a remarkable increase of long-chain (C16-18) acylcarnitines was detected on tandem mass spectrometry (TMS). Decreased CPT-II expression was detected in the liver, heart and kidney of the patient. Furthermore, del1737C, a novel mutation of the CPT-II gene, was detected as well as a known GA transition at codon 174. Eventually, laboratory and autopsy findings led to diagnosis of the neonatal form of CPT-II deficiency. TMS can be expected to be widely used to detect metabolic disorders in neonates.

An unusual cause of neonatal coagulopathy and liver disease.

Congenital thyrotoxicosis is a rare and potentially fatal illness. We report a case in a preterm infant delivered to a mother known to have autoimmune endocrine disease. Diagnosis was difficult because the infant's presenting symptoms and signs closely resembled congenital viral infection with co-existent hepatic dysfunction and coagulopathy. The associated hepatic dysfunction was so severe that liver biopsy was scheduled before the diagnosis emerged. A high degree of clinical suspicion coupled with prenatal identification of pregnancies at risk of complication by congenital thyrotoxicosis is imperative to facilitate prompt diagnosis and treatment.

Hyporegenerative anemia associated with Rh hemolytic disease: treatment failure of recombinant erythropoietin.

A postnatal hyporegenerative anemia may complicate Rh hemolytic disease. Intramedullary hemolysis, bone marrow suppression, and erythropoietin deficiency have been implicated etiologically. Treatment with recombinant erythropoietin (r-EPO) has yielded encouraging preliminary results. The authors describe an infant with Rh isoimmunization who developed severe hyporegenerative anemia unresponsive to a 5-week course of r-EPO. Two additional doses at 12 weeks resulted in brisk reticulocytosis, coinciding with a 16-fold decline in the anti-Rh(D) antibody titer. Thus, treatment with r-EPO may be ineffective when anti-Rh(D) antibody titers are high. The authors also show that erythropoietin deficiency in hyporegenerative anemia is not as frequent and severe as originally thought.

Hemangiomatosis neonatal difusa / Neonatal disseminated hemangiomatosis

Introducción. La hemangiomatosis neonatal difusa (HND) es un síndrome raro que consiste en la aparición de múltiples hemangiomas cutáneos pequeños y sobreelevados, los cuales pueden estar asociados a hemangiomas en el hígado, pulmones, tracto gastrointestinal, laringe y sistema nervioso central entre otros. Estos hemangiomas pueden estar presentes al momento del nacimiento y con el transcurso del tiempo pueden desarrollarse nuevos hemangiomas. De existir hemorragias importantes, estos niños pueden fallecer; sin embargo, se han reportado casos de involución espontánea. Actualmente no se cuenta con ningún método que permita predecir la evolución final de estos niños, pero con el advenimiento de esteroides e interferón su pronóstico se ha favorecido.Caso clínico. Se reporta el caso de una recién nacida quien presentó hemangiomas cutáneos múltiples al nacimiento corroborado mediante biopsia. Se investigaron asociaciones y se detectó un hemangioma hepático mediante ultrasonografía Doppler, tomografía axial computada y arteriografía. Recibió tratamiento con hidroclorotiazida e interferón, y evolucionó satisfactoriamente. Conclusión. El diagnóstico y tratamiento oportuno tanto de la HND como de las asociaciones viscerales que comprometen la vida, favorecen su evolución y pronóstico. Hemangiomatosis neonatal difusa; esteroides; interferón.

A novel deficiency of mitochondrial ATPase of nuclear origin.

We report a new type of fatal mitochondrial disorder caused by selective deficiency of mitochondrial ATP synthase (ATPase). A hypotrophic newborn from a consanguineous marriage presented severe lactic acidosis, cardiomegaly and hepatomegaly and died from heart failure after 2 days. The activity of oligomycin-sensitive ATPase was only 31-34% of the control, both in muscle and heart, but the activities of cytochrome c oxidase, citrate synthase and pyruvate dehydrogenase were normal. Electrophoretic and western blot analysis revealed selective reduction of ATPase complex but normal levels of the respiratory chain complexes I, III and IV. The same selective deficiency of ATPase was found in cultured skin fibroblasts which showed similar decreases in ATPase content, ATPase hydrolytic activity and level of substrate-dependent ATP synthesis (20-25, 18 and 29-33% of the control, respectively). Pulse-chase labelling of patient fibroblasts revealed low incorporation of [(35)S]methionine into assembled ATPase complexes, but increased incorporation into immunoprecipitated ATPase subunit beta, which had a very short half-life. In contrast, no difference was found in the size and subunit composition of the assembled and newly produced ATPase complex. Transmitochondrial cybrids prepared from enucleated fibroblasts of the patient and rho degrees cells derived from 143B. TK(-)human osteosarcoma cells fully restored the ATPase activity, ATP synthesis and ATPase content, when compared with control cybrids. Likewise, the pattern of [(35)S]methionine labelling of ATPase was found to be normal in patient cybrids. We conclude that the generalized deficiency of mitochondrial ATPase described is of nuclear origin and is caused by altered biosynthesis of the enzyme.

[Anomalies of umbilical vein in the fetus. A case report and review of the literature]. / Les anomalies de la veine ombilicale intra-abdominale chez le foetus. A propos d'un cas et rèvue de la littérature.

Abnormal connexion of the umbilical vein in the inferior vena cava was diagnosed in a fetus at 18 weeks' gestation. Associated anomalies included nuchal and axillary lymphangiectasia, hypertrophic cardiomyopathy and hepatomegaly. Neonatal death occurred after spontaneous vaginal delivery at 25 weeks. A review of the literature summarizes the diagnostic criteria and associated anomalies.

[Current trends in the treatment of giant nonparasitic cysts of the liver]. / Attuali orientamenti sul trattamento delle cisti non parassitarie giganti del fegato.

The authors report 10 cases of giant non-parasitic congenital cysts of the liver (7.7-25 cm in size). All the patients were symptomatic; preoperative ultrasonography was diagnostic in all cases allowing to discover the cyst. Six patients underwent partial resection of the cyst (in one of these a cystojejunostomy was performed), while atypical hepatic resection was performed in two cases, enucleation in one and left lobectomy in another case. No evidence of malignant degeneration was found in the histologic study of the specimens. No mortality nor morbidity were registered. All patients were followed up for 1-20 years and no recurrences were found. The authors point out that partial resection of the cyst is a safe operation with good immediate and long-term results.

Ectopia cordis in a Nigerian child.

A female infant is described with a complete ectopia cordis and a single atrium who presented four hours after birth. There was complete deficiency of the sternum with the absence of pericardium over the heart. There was an associated omphalocele containing an enlarged liver. The infant died 45 hours after birth following an attempt to provide tissue covering. Additional intracardiac anomalies included a ventricular septal defect overriding aorta and total anomalous venous drainage.

[Successful insulin therapy in lipoatrophic diabetes]. / Erfolgreiche Insulintherapie bei lipatrophischem Diabetes.

Two and a half years after manifestation of treatment-refractory lipoatrophic diabetes a 16-year-old girl had blood-sugar levels of about 500 mg/dl and hypertriglyceridaemia with fasting levels of about 3000 mg/dl, while there was no increase in ketone bodies. All the clinical, histological and radiological findings were those of generalized fatty tissue atrophy. In addition, she had marked axillary and periorbital acanthosis nigricans. Main symptoms were fatigue, weakness and excessive appetite. Intravenous insulin of at first 1200 IU daily reduced blood-sugar levels to normal. A good metabolic state was maintained by intensive insulin treatment with four intramuscular injections daily. On a dosage of 600-700 IU daily the HbA1 value dropped from 16.7% to 7.8%, triglyceride concentration to 300-400 mg/dl. The symptoms also regressed with normalization of the metabolic state.