Pre and postnatal diagnosis of congenital portosystemic shunt: Impact of interventional therapy.

INTRODUCTION: Congenital portosystemic shunts (CPSS) are rare vascular malformations that can lead to severe complications. With advanced imaging techniques, diagnosis is becoming more feasible occurring in fetal life. Different approaches have been adopted to manage these cases, with an increased utilization of interventional therapy recently. This cohort aims to describe the course of children diagnosed with CPSS and the impact of interventional therapy on the outcome. METHODS: Retrospective chart review was done for all patients who were diagnosed with CPSS in our institution between January 2006 and December 2015. RESULTS: Six patients were diagnosed with CPSS. During this period, 8,680 mothers carrying 9548 fetuses underwent fetal ultrasound examinations. Three patients were diagnosed antenatally at a median [IQ] gestational age of 33 [26-33] weeks, and three patients were diagnosed postnatally at 0, 2, and 43 months, respectively. At a median follow-up of 87 [74-110] months, 5 patients are alive; 4 of whom had received transcatheter closure for different indications, and one who had spontaneous resolution of her CPSS. One infant died at the age of 6 weeks secondary to sepsis. CONCLUSION: CPSS can result in significant complications in children. Interventional therapy is feasible at any age group, but long-term follow-up is warranted.

Oldest co-occurrence of Varanus and Python from Africa-first record of squamates from the early Miocene of Moghra Formation, Western Desert, Egypt.

Lizard and snake remains from the early Miocene (Burdigalian) of the Moghra Formation, Egypt, are described herein. This material comprises the first fossil remains of squamates recovered from the otherwise rich and well known vertebrate assemblage of Moghra. The material pertains to two different genera, the varanid lizard Varanus and the pythonid snake Python and adds to the so far rather poorly known squamate fossil record from Africa. On the basis of the new remains, Moghra marks the oldest so far described co-occurrence of Varanus and Python in the African continent. The close sympatry of these two genera in the African fossil record is thoroughly analyzed and discussed, a co-existence, which is still widespread in the extant herpetofauna of the continent. Situated rather close to the so called "Levantine Corridor" and dated at the Burdigalian, practically when Afro-Arabia collided with Eurasia, the Moghra squamate assemblage offers the potential of important insights in the biogeography and dispersal events of vertebrate groups during the early Miocene.

Hypoxia due to intrapulmonary vascular dilatation in a toddler with a congenital portacaval shunt: case report.

BACKGROUND: The term hepatopulmonary syndrome typically applies to cyanosis that results from "intrapulmonary vascular dilatation" due to advanced liver disease. Similar findings may result from a congenital portosystemic shunt without liver disease. An adverse consequence of such shunts is intrapulmonary vascular dilatation, which affects the microvascular gas exchange units for oxygen. CASE PRESENTATION: Here, we describe a toddler with chronic cyanosis, exercise intolerance, and finger clubbing due to a malformation shunt between the portal vein and the inferior vena cava. A transcatheter embolization of the shunt resulted in resolution of his findings. CONCLUSIONS: Congenital portosystemic shunts need to be considered in the differential diagnosis of cyanosis.

Diagnosis and treatment of late-onset Pompe disease in the Middle East and North Africa region: consensus recommendations from an expert group.

BACKGROUND: Pompe disease is a rare autosomal recessive disorder caused by a deficiency of the lysosomal enzyme alpha-glucosidase responsible for degrading glycogen. Late-onset Pompe disease has a complex multisystem phenotype characterized by a range of symptoms. METHODS: An expert panel from the Middle East and North Africa (MENA) region met to create consensus-based guidelines for the diagnosis and treatment of late-onset Pompe disease for the MENA region, where the relative prevalence of Pompe disease is thought to be high but there is a lack of awareness and diagnostic facilities. RESULTS: These guidelines set out practical recommendations and include algorithms for the diagnosis and treatment of late-onset Pompe disease. They detail the ideal diagnostic workup, indicate the patients in whom enzyme replacement therapy should be initiated, and provide guidance on appropriate patient monitoring. CONCLUSIONS: These guidelines will serve to increase awareness of the condition, optimize patient diagnosis and treatment, reduce disease burden, and improve patient outcomes.

Perinatal outcome of congenital heart disease in a population with high consanguinity.

OBJECTIVE: To report the perinatal pattern and outcome of fetuses with congenital heart disease (CHD) in consanguineous marriages. METHODS: Retrospective chart review was performed for fetuses undergoing fetal echocardiography (FE) in our institution. The primary outcome was survival at 28 days after birth. RESULTS: Between 1 January 2005 and 31 December 2010, 1950 pregnant women carrying 2151 fetuses underwent a total of 2828 FEs. CHD was diagnosed in 152 fetuses (7.1%), and perinatal outcome was available in 120, among which 78 (65%) had consanguineous parents. Thirteen fetuses died in utero, while 86 (71.7%) survived. The most prevalent lesions included left heart obstruction (25.8%), conotruncal malformations (21.7%), septal defects (18.3%), and cardiomyopathy (15.8%). Correct diagnosis was achieved in 92.2% of the cases. Extracardiac malformations occurred in 48.3% of the fetuses and were associated with increased mortality regardless of the type of CHD (P<0.001, odds ratio 6.8, 95% confidence interval 2.7-17.5). CONCLUSION: Joint FE clinics detect most CHD with high accuracy. Consanguinity contributes to a higher prevalence of fetal cardiac and non-cardiac malformations. The presence of extracardiac anomalies is associated with an increase in perinatal mortality.

Enzyme-replacement therapy in life-threatening hypophosphatasia.

BACKGROUND: Hypophosphatasia results from mutations in the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Inorganic pyrophosphate accumulates extracellularly, leading to rickets or osteomalacia. Severely affected babies often die from respiratory insufficiency due to progressive chest deformity or have persistent bone disease. There is no approved medical therapy. ENB-0040 is a bone-targeted, recombinant human TNSALP that prevents the manifestations of hypophosphatasia in Tnsalp knockout mice. METHODS: We enrolled infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia in a multinational, open-label study of treatment with ENB-0040. The primary objective was the healing of rickets, as assessed by means of radiographic scales. Motor and cognitive development, respiratory function, and safety were evaluated, as well as the pharmacokinetics and pharmacodynamics of ENB-0040. RESULTS: Of the 11 patients recruited, 10 completed 6 months of therapy; 9 completed 1 year. Healing of rickets at 6 months in 9 patients was accompanied by improvement in developmental milestones and pulmonary function. Elevated plasma levels of the TNSALP substrates inorganic pyrophosphate and pyridoxal 5'-phosphate diminished. Increases in serum parathyroid hormone accompanied skeletal healing, often necessitating dietary calcium supplementation. There was no evidence of hypocalcemia, ectopic calcification, or definite drug-related serious adverse events. Low titers of anti-ENB-0040 antibodies developed in four patients, with no evident clinical, biochemical, or autoimmune abnormalities at 48 weeks of treatment. CONCLUSIONS: ENB-0040, an enzyme-replacement therapy, was associated with improved findings on skeletal radiographs and improved pulmonary and physical function in infants and young children with life-threatening hypophosphatasia. (Funded by Enobia Pharma and Shriners Hospitals for Children; ClinicalTrials.gov number, NCT00744042.).

Very high serum ferritin levels in three newborns with Kawasaki-like illness.

Kawasaki disease (KD) is an inflammatory condition of unknown etiology that affects children, with a peak incidence in the second year of life. KD is uncommon in the first year of life and is rare in the newborn period. The present report describes three newborn infants who were admitted to hospital with fever and nearly identical clinical features of generalized inflammation. The presentations did not meet the criteria for KD; however, all three patients responded promptly and completely to intravenous immunoglobulin treatment. Specifically, the association of these presentations with very high levels of serum ferritin is reported. The authors propose that this clinical syndrome represents a variant of KD, and that serum ferritin level may be a useful marker in diagnosing KD and its variants. Additionally, the association of this clinical picture with very high serum ferritin levels raises the possibility of a link with hemophagocytic lymphohistiocytosis.

La maladie de Kawasaki (MK) est un problème inflammatoire qui touche les enfants et dont l'étiologie est inconnue. Le pic d'incidence se produit pendant la deuxième année de vie. La MK est peu courante pendant la première année de vie et rare pendant la période néonatale.Dans le présent rapport, les auteurs décrivent trois nouveau-nés fiévreux admis à leur hôpital et dont les manifestations cliniques d'inflammation généralisée étaient presque identiques. Les présentations ne respectaient pas les critères de MK. Cependant, les trois patients ont réagi rapidement et complètement au traitement à l'immunoglobuline par voie intraveineuse. Plus précisément, les auteurs rendent compte de l'association de cette présentation à de très forts taux de ferritine sérique. Ils postulent que ce syndrome clinique représente une variante de la MK et que le taux de ferritine sérique peut constituer un marqueur utile pour diagnostiquer la MK et ses variantes. De plus, l'association de ce bilan clinique à des taux de ferritine sérique très élevés soulève la possibilité d'un lien avec la lymphohistiocytose hémophagocytaire.

New and known mutations associated with inborn errors of metabolism in a heterogeneous Middle Eastern population.

OBJECTIVE: To identify the mutations underlying a number of inborn errors of metabolism (IEM) disorders among United Arab Emirates (UAE) residents. METHODS: Molecular diagnostic and bioinformatics tools were used to identify the causative mutations of IEM disorders from multi-ethnic patients residing in UAE. The study was conducted in Al-Ain, UAE, between April 2009 and September 2010. This is a case series retrospective study where patients attending the metabolic clinic at Tawam Hospital were recruited. Thirty patients and 26 parents were included. RESULTS: We present evidence in the UAE of 7 new mutations and 19 mutations that have previously been reported in other populations, all causing a number of common IEM disorders, including phenylketonuria, maple syrup urine disease, glycogen storage diseases, beta-ketothiolase deficiency, and Zellweger syndrome among many others. CONCLUSION: Reflecting the diverse ethnic groups residing in the UAE, we found mutations in several different population groups. However, consanguinity is evident in most cases. This report is of utmost importance for taking the necessary steps toward the prevention of inherited disorders, not just in the UAE, but anywhere in the world where these Arab and Asian populations reside, or where consanguinity is a cultural norm.

Antenatal diagnosis of pompe disease by fetal echocardiography: impact on outcome after early initiation of enzyme replacement therapy.

Hypertrophic cardiomyopathy (HCM) affects most infants with Pompe disease (PD), and may serve as a marker for its antenatal diagnosis (ANDx) by fetal echocardiography (FE). Fetuses diagnosed with HCM between 2006 and 2009 were included in this study. HCM, defined as Z-score of mean left ventricular wall thickness (LVWT) and/or mass (LVM) above 2, was detected in 5/1,268 fetuses (0.39%) carried by 1,137 pregnant women referred for FE. Three fetuses (0.24%) had postnatal confirmation of PD. Their gestational age and fetal weight at diagnosis was (mean ± standard deviation) 31 ± 3.6 weeks and 1.9 ± 0.2 kg, respectively. Fetal Z-score of LVM and LVWT was 3.8 ± 0.9 and 3.1 ± 0.6, respectively. Postnatally, acid α-glucosidase (GAA) enzyme activity was nearly absent in all patients, 2 were homozygous for the mutation 1327-2A>G in the GAA gene, and 1 was homozygous for 340insT. Enzyme replacement therapy (ERT) was initiated 4.9 ± 7.8 days after birth (range 2 h-14 days), and continued every 2 weeks. Two infants are alive at 4 and 31 months, and one died of aspiration pneumonia at 19 months. Cardiac hypertrophy resolved after 10-12 weeks of ERT in all patients, and none required any respiratory support. One patient had normal neurodevelopmental assessment at 25 months, and one had severe global delay at 15 months before death. ANDx of PD by FE is feasible based on fetal HCM. It promotes early initiation of ERT which may improve outcome in some patients. However, larger studies and longer follow-ups are required.

Inseparable thoraco-omphalopagus twins.

Conjoined twins occur at the rate of 1 in 50 to 200,000 live births, and 75% of these share the thorax (thoracopagus) or the thorax and upper abdomen (thoraco-omphalopagus), resulting in cardiac and hepatic sharing. Antenatal diagnosis can delineate the cardiac anatomy and provide parental counseling on whether separation is possible after birth. In the majority of cases, thoracopagus twins have a complex cardiac anatomy and share a common pericardial sac. Separation and survival depend on the extent to which the cardiac chambers and conduction system are fused. When the twins share the atria, ventricles, or both, death is inevitable even if surgical separation is occasionally attempted.

Reversal of iron-induced dilated cardiomyopathy during therapy with deferasirox in beta-thalassemia.

A 15-year-old male with beta-thalassemia major developed dilated cardiomyopathy secondary to iron-overload (Z-scores of left ventricle (LV) dimensions >3, ejection fraction (EF) 33%). Treatment with deferoxamine was unsuccessful, presumably due to poor compliance. After 15 months of using deferasirox (DFX), LV end-diastolic dimension normalized (Z-scores <2), and EF improved to 58%. We conclude that treatment with DFX resulted in a reversal of iron-induced cardiomyopathy.

Churg-Strauss syndrome presenting as an abdominal mass in a non-asthmatic child.

A 2-year-old boy presented with an abdominal mass and was diagnosed as Churg-Strauss syndrome (CSS). There was no history of asthma. He developed fatal gastro-intestinal disease, despite treatment with corticosteroids and cyclophosphamide. CSS is extremely rare in young children and gastro-intestinal involvement might carry a worse prognosis than in adults.

A novel early onset lethal form of catecholaminergic polymorphic ventricular tachycardia maps to chromosome 7p14-p22.

INTRODUCTION: Previously, autosomal dominant catecholaminergic polymorphic ventricular tachycardia (CPVT [1]) was mapped to chromosome 1q42-43 with identification of pathogenic mutations in RYR2. Autosomal recessive CPVT (2) was mapped to chromosome 1p13-21, leading to the identification of mutations in CASQ2. In this study, we aimed to elucidate clinical phenotypes of a new variant of CPVT (3) in an inbred Arab family and also delineate the chromosomal location of the gene causing CPVT (3). METHODS AND RESULTS: In a highly inbred family, clinical symptoms of CPVT appeared early in childhood (7-12 years) and in three of the four cases, the first appearance of symptoms turned into a fatal outcome. Parents of the affected children were first-degree cousins and without any symptoms. Segregation analysis suggested an autosomal recessive inheritance. A genome-wide search using polymorphic DNA markers mapped the disease locus to a 25-Mb interval on chromosome 7p14-p22. A maximal multipoint LOD score of 3.17 was obtained at marker D7S493. Sequencing of putative candidate genes, SP4, NPY, FKBP9, FKBP14, PDE1C, and TBX20, in and around this locus, did not reveal any mutation. CONCLUSIONS: We have identified a novel highly malignant autosomal recessive form of CPVT and mapped this disorder to a 25-Mb interval on chromosome 7p14-p22.

Octreotide and low-fat breast milk in postoperative chylothorax.

Chylothorax is a rare complication following cavo-pulmonary connection and can lead to significant morbidity in infants and young children. We report here the case of a 3-month-old infant who underwent bilateral cavo-pulmonary connections, and developed severe chylothorax refractory to the usual conservative and surgical treatments. His chylothorax resolved after using a combination of parenteral octreotide (Sandostatin, Novartis Pharmaceuticals, East Hanover, NJ) and low-fat breast milk.