Ross-Konno and Endocardial Fibroelastosis Resection After Hybrid Stage I Palliation in Infancy: Successful Staged Left-Ventricular Rehabilitation and Conversion to Biventricular Circulation After Fetal Diagnosis of Aortic Stenosis

We report a patient who presented during fetal life with severe aortic stenosis, left-ventricular dysfunction, and endocardial fibroelastosis (evolving hypoplastic left heart syndrome). Management involved in utero and postnatal balloon aortic valvuloplasty for partial relief of obstruction and early postnatal hybrid stage I palliation until recovery of left-ventricular systolic function had occurred. The infant subsequently had successful conversion to a biventricular circulation by combining resection of endocardial fibroelastosis with single-stage Ross-Konno, aortic arch reconstruction, hybrid takedown, and pulmonary artery reconstruction.     

Familial nonobstructive cardiomyopathy with endocardial fibroelastosis beyond infancy.

A 10-year-old boy with congestive heart failure died in five months in spite of comprehensive medical treatment. Autopsy showed patchy areas of endocardial fibroelastosis of the left ventricle. The sister of this patient had followed a similar course at 13 years of age with death within six months of the onset of congestive failure. Her postmortem examination also showed endocardial fibroelastosis. The clinical presentation of familial endocardial fibroelastosis in the preteen and teenage years is a rare event. Probably the endocardial fibroelastosis was secondary to a familial nonobstructive cardiomyopathy.     

Mucopolysaccharidosis type I in Morocco: clinical features and genetic profile]

BACKGROUND: Mucopolysaccharidoses (MPS) are inherited metabolic disorders due to lysosomal enzyme deficiencies, leading to glycosaminoglycan accumulation in lysosomes of different tissues. The aim of this study was to characterize MPS types, particularly MPS I, which are difficult to differentiate by clinical features. PATIENTS AND METHODS: Over a period of three years (June 1996-May 1999), 16 Moroccan patients (3-20 years old) with MPS were investigated. Twelve of them came from the Souss region. In subjects with suspected clinical MPS I or II, the diagnosis was confirmed by biochemical investigations, which included the quantification of total glycosaminoglycans (GAGs) released in urine, their identification, and the assay of alpha-L-iduronidase activity in leucocytes. A molecular analysis was performed in parallel, to provide the genetic proof of the diagnosis. RESULTS: These 16 patients belonged to 12 families, nine of which were consanguineous (75%). Twelve patients had Hurler syndrome and three had Hurler/Scheie's syndrome; no case of Scheie's syndrome was observed. Short stature, coarse face, organomegaly, hernia, cardiac disease, mental delay and dysostosis were observed in variable degrees. We report three cases without corneal clouding. Increased total urinary GAGs, identified as dermatan sulfate and heparan sulfate by thin-layer chromatography and total deficiency of alpha-L-iduronidase activity, were noted in studied subjects. At the molecular level the P533R mutation was detected in 24 among 26 alleles studied. CONCLUSION: It is now possible to perform the screening of MPS I and II in Morocco by analysis of clinical, radiologic observations and biological investigation. The predominance of P533R mutation could permit the screening of healthy heterozygotes and genetic counselling for families of Moroccan descent.     

Endocardial fibroelastosis of the left ventricle in a patient with Alagille syndrome

We present a case of a 6 week old infant with Alagille syndrome. Cardiological evaluation revealed peripheral pulmonary arterial stenosis and left ventricular endocardial fibroelastosis. While peripheral pulmonary arterial stenosis are typical for the syndrome this is the first case reported with endocardial fibroelastosis. Complex cardiac malformations may worsen the prognosis in Alagille syndrome. They require early diagnosis and therapy.     

Heart transplantation in infants--a new option

Nowadays orthotopic heart transplantation is world wide accepted as a therapeutic concept in endstage congestive heart failure. Concerning infants, there are still major objections against this kind of therapy and especially in our country exists only very limited experience. Since march 1988 we have performed an orthotopic heart transplantation in 10 pediatric patients: 5 infants (2-16 years of age) with congestive cardiomyopathy, 1 newborn with endocardial fibroelastosis, 3 newborns with hypoplastic left heart syndrome, and finally 1 infant at the age of 2 years with AV-canal and hypoplastic left ventricle. Until now 6 infants survived and are all at home and in good clinical condition. There have been no signs for chronic rejection or graft atherosclerosis up till now. As demonstrated in the example of the newborn, in whom we performed the first successfully orthotopic heart transplantation in Germany, the clinical course and quality of life are superior to those after other palliative procedures in complex cardiac malformations.     

Endocardial fibrosis and hydrops fetalis in a premature infant

We describe a premature neonate with endocardial fibrosis associated with hydrops fetalis. The infant did not have any other cardiac disorder and expired with congestive heart failure when five days old. Endocardial fibroelastosis has been previously described in neonates but is rare and is usually associated with other cardiac malformations. In only two previous reports was endocardial fibroelastosis associated with hydrops and in both of these cases there were also valvular deformities. We also discuss the possible significance of this association.     

Combined enzyme replacement and haematopoietic stem cell transplantation in Hurler syndrome

We report the long-term follow-up of successful treatment of mucopolysaccharidosis type I H (MPS IH, Hurler syndrome) with combined enzyme replacement therapy and haematopoietic progenitor stem cell transplant.     

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目的 探讨小儿左冠状动脉起源于肺动脉(ALCAPA)所致心脏扩大病例的误诊原因,总结诊断经验.方法 回顾性分析1996年7月至2009年1月广东省心血管病研究所22例小儿ALCAPA所致心脏扩大的误诊病例.均行心电图、X线胸片、超声心动图检查,8例行心脏CT检查,14例行心导管检查及造影,21例进行了外科手术治疗.结果 ≤1岁患儿10例中,6例误诊为心内膜弹力纤维增生痘,3例误诊为扩张型心肌病,1例误诊为先天性二尖瓣脱垂并关闭不全.>1岁患儿12例中,4例误诊为扩张型心肌病,3例误诊为心内膜弹力纤维增生症,2例误诊为先天性二尖瓣脱垂并关闭不全,1例误诊为右冠状动脉右心室瘘,1例误诊为川崎病,1例误诊为动脉导管未闭.结论 小儿ALCAPA所致心脏增大病例容易误诊为心内膜弹力纤维增生症、扩张型心肌病、先天性二尖瓣脱垂等疾病,左冠状动脉起源于肺动脉后方偏右的病例更易误诊.提高对ALCAPA的认识、超声或CT检查中仔细探查冠状动脉及其起源对避免误诊至关重要.     

Outcome in six children with mucopolysaccharidosis type IH, Hurler syndrome, after haematopoietic stem cell transplantation (HSCT)

AIM: To follow-up six children with severe mucopolysaccharidosis type IH, Hurler syndrome, who were treated before 24 months of age with haematopoietic stem cell transplantation. METHODS: In Sweden, during the last 10-year period, six consecutive children born with severe mucopolysaccharidoses type IH have been successfully transplanted using matched unrelated donors between the ages of 11 and 24 months (mean age 18 months). Three children received intravenous enzyme replacement therapy once a week, from diagnosis until engraftment of their bone marrow. RESULT: Two children developed chimerism and a progressive increase in recipient cells and later received a successful re-transplantation. One to two years after transplantation the children demonstrated some developmental delays in cognitive function. Latterly this was followed by normalization. Orthopaedic operations on the spine and hips and carpal tunnel syndrome were still required following transplantation. Cardiac valve involvement remained progressive in the children. CONCLUSION: The outcome of six children in this study confirms that early haematopoietic stem cell transplantation in mucopolysaccharidosis type I, Hurler syndrome, preserves an affected child's mental ability. Consequently, it is essential that clinical recognition and early diagnosis take place, providing an additional challenge to paediatricians treating this condition.     

PROBABLE SECOND FETUS WITH MARLES-CHUDLEY SYNDROME: CARDIAC CALCIFICATIONS WITH ULNAR DEFICIENCY AND ABSENT/HYPOPLASTIC THUMBS

In 1990 Marles and Chudley reported on an infant with absent ulnae and concomitant radial hypoplasia, oligodactyly, hydrops fetalis, and apparent endocardial fibroelastosis (EFE) and, on the basis of phenotype and parental consanguinity, postulated autosomal recessive inheritance. Recently we were privileged to study parts of a fetus who had presented at ultrasonography with cardiac calcifications, micrognathia, and severe ulnar dysgenesis. The small pieces of heart we received showed neither endocardial fibroelastosis nor calcifications. Thus, we had initial doubts that we were dealing with the Marles-Chudley syndrome. However, a review by Chudley of the heart findings in his cases did show the calcifications usually seen in primary or secondary EFE. The parents of Dr. Chudley's patient were Filipino; the father of our patient was a Samoan. This suggests that there exists a gene for autosomal recessive Marles-Chudley syndrome in the Polynesian population with pleiotropic effects on upper limb development and cardiac histogenesis.     

Probable second fetus with Marles-Chudley syndrome: cardiac calcifications with ulnar deficiency and absent/hypoplastic thumbs

In 1990 Marles and Chudley reported on an infant with absent ulnae and concomitant radial hypoplasia, oligodactyly, hydropsfetalis, and apparent endocardial fibroelastosis (EFE) and, on the basis of phenotype and parental consanguinity, postulated autosomal recessive inheritance. Recently we were privileged to study parts of a fetus who had presented at ultrasonography with cardiac calcifications, micrognathia, and severe ulnar dysgenesis. The small pieces of heart we received showed neither endocardial fibroelastosis nor calcifications. Thus, we had initial doubts that we were dealing with the Marles-Chudley syndrome. However, a review by Chudley of the heart findings in his cases did show the calcifications usually seen in primary or secondary EFE. The parents of Dr. Chudley's patient were Flipino; the father of our patient was a Samoan. This suggests that there exists a gene for autosomal recessive Marles-Chudley syndrome in the Poynesian population with pleiotropic effects on upper limb development and cardiac histogenesis.     

MUCOLIPIDOSIS II (I-CELL DISEASE) A Clinical and Biochemical Study

The diagnosis of mucolipidosis I1 (I-cell disease) was made in a patient with a Hurler like appearance but only borderline muco-polysacchariduria. The cultured fibroblasts of high doses of prednison, which resulted in a further increase in the enzyme activity. On the ultrastructural level there was the storage of polymorphous material in the liver and in the peripheral nerve. Vacuolated cells were present in the peripheral leucocytes and in the bone marrow. These findings indicate that the lysosmal enzyme depletion in the cells in the patient could be similar to that found in cultured cells. However, the clinical picture could also be caused by the excess activity of lysosomal enzymes in the extracellular fluids which are able to degrade the matrix substance of the connective tissues and could mimic a mucopolysaccharidosis.     

Cardiac functional and histopathologic findings in humans and mice with mucopolysaccharidosis type I: implications for assessment of therapeutic interventions in hurler syndrome

Hurler syndrome (mucopolysaccharidosis type I [MPS I]) is a uniformly lethal autosomal recessive storage disease caused by absence of the enzyme alpha-l-iduronidase (IDUA), which is involved in lysosomal degradation of sulfated glycosaminoglycans (GAGs). Cardiomyopathy and valvar insufficiency occur as GAGs accumulate in the myocardium, spongiosa of cardiac valves, and myointima of coronary arteries. Here we report the functional, biochemical, and morphologic cardiac findings in the MPS I mouse. We compare the cardiac functional and histopathological findings in the mouse to human MPS I. In MPS I mice, we have noted aortic insufficiency, increased left ventricular size, and decreased ventricular function. Aortic and mitral valves are thickened and the aortic root is dilated. However, murine MPS I is not identical to human MPS I. Myointimal proliferation of epicardial coronary arteries is unique to human MPS I, whereas dilation of aortic root appears unique to murine MPS I. Despite the differences between murine and human MPS I, the murine model provides reliable in vivo outcome parameters, such as thickened and insufficient aortic valves and depressed cardiac function that can be followed to assess the impact of therapeutic interventions in preclinical studies in Hurler syndrome.     

Endocardial Fibroelastosis in Growth-Discordant Monozygotic Twins

Two cases of fetal endocardial fibroelastosis are reported in the larger of growth-discordant monozygotic twins. The growth discordance in these two cases is regarded as a manifestation of twin-twin transfusion syndrome, but other causes are considered and the difficulties posed by the observed placental vascular anatomy are discussed. The literature on endocardial fibroelastosis in multiple pregnancy is briefly reviewed, and the relationship of endocardial fibroelastosis to the cardiovascular compromise seen in twin-twin transfusion syndrome is considered. Received August 11, 1997; accepted December 31, 1997.     

Laronidase for cardiopulmonary disease in Hurler syndrome 12 years after bone marrow transplantation

A patient with severe mucopolysaccharidosis type I (Hurler syndrome) underwent bone marrow transplantation twice (at the ages of 2 and 2.5 years), both times with his HLA-identical heterozygous brother as the donor. Between the ages of 10 and 14 years, despite 92% donor engraftment and 50% normal α-L-iduronidase activity, he developed progressive respiratory failure with severe pulmonary arterial hypertension, upper airway obstruction, and interstitial lung disease. Noninvasive ventilation and weekly laronidase therapy were initiated. Within 24 months, his mean pulmonary artery pressure was within the upper limit of normal and interstitial lung disease and airway obstruction improved markedly. He went from using a wheelchair to having full ambulation, he no longer required daytime ventilation, and his quality-of-life scores (Child Health Assessment Questionnaire) significantly improved.     

Familial hepatic venoocclusive disease with probable immune deficiency.

Five infants from three families died between the ages of 2 and 7 months with venocclusive disease of the liver. No dietary, toxic, or other extrinsic cause was uncovered. In one family the first infant was breast-fed; the second one received no breast milk. In two of the families the parents were cousins. All infants had some evidence of immune deficiency, including hypogammaglobulinemia in at least three, multiple infections especially Pnumocystis carnii and enteroviruses, and lymphoid tissues devoid of germinal centers and mature plasma cells. Other findings in some of the infants, not previously recorded in venoocclusive disease, were microcephaly, multiple small cerebral softening, and left atrial endocardial fibrosis. A congenital cause for venoocclusive disease is suggested in these cases.     

Left ventricular pannus causing inflow obstruction late after mitral valve replacement for endocardial fibroelastosis

A case of mitral stenosis following mitral valve replacement in a patient with endocardial fibroelastosis is reported. A 14-year-old boy presented with cardiac failure. He had been diagnosed as having endocardial fibroelastosis at the age of 7 months and had undergone resection of endocardial fibrous tissue in the left ventricle at that time. Five years later his mitral valve was resected owing to mitral stenosis, with Bjork-Shiley valve replacement. Cross-sectional echocardiography on this admission showed restrictive left ventricular inflow due to a thickened immobile prosthetic valve with severely dyskinetic left ventricle (ejection fraction 8%). The electrocardiogram showed atrioventricular reentry tachycardia. Despite direct current cardioversion and continual amiodarone infusion he suffered a cardiac arrest and died 12 days after admission. Postmortem examination showed left ventricular endocardial fibroelastosis with severe inflow obstruction due to the formation of a complete fibrous ring of pannus/fibrosis around the prosthetic margin on the ventricular aspect of the left ventricle. This complication has not previously been described in children after mitral valve replacement.     

alpha1-Antitrypsin deficiency and liver disease in children.

This report describes the clinical, biochemical, and hepatic morphologic findings in ten children with severe serum alpha1-antitrypsin deficiency. Genetic protease inhibitor (Pi) phenotyping, using acid-starch gel and crossed antigen-antibody electrophoresis, demonstrated Pi phenotype ZZ in all our cases. In eight patients, manifestations of liver disease appeared during the first year of life. The case reports show that alpha1-antitrypsin deficiency should be suspected in any child with neonatal hepatitis, unexplained hepatomegaly or splenomegaly, or cirrhosis. In our report, one infant is normal at age 6 months, and one infant had progressive hepatic damage that culminated in liver failure and death at age 6 months. The variable clinical course and prognosis for infants with severe alpha1-antitrypsin deficiency is well illustrated by these two infants.     

MR findings of endocardial fibroelastosis in children

Background Endocardial fibroelastosis (EFE) is characterized by a diffuse white fibrous tissue lining the endocardium. The diagnosis is difficult to establish because clinical symptoms and electrocardiographic findings are nonspecific. Surgical resection of EFE requires the establishment of the diagnosis and delineation of the extent of the fibrotic changes. Objective To describe the use of MRI in the assessment of EFE in children. Materials and methods Three children after surgery for aortic stenosis who were suspected of having EFE were evaluated by echocardiography and MRI. The MR evaluation consisted of black-blood, triple IR, bright-blood, perfusion and myocardial delayed-enhancement sequences. EFE was confirmed at surgery in all patients. Results Echocardiograms demonstrated vigorous systolic function but substantial diastolic dysfunction of the left ventricle in all. Mild endocardial brightening of the anterior septum, anterior wall, or papillary muscles was present in two. No study was thought to be diagnostic of endocardial fibrosis. On MRI EFE manifested at the endocardial surface as a rim of hypointense signal in the perfusion sequences and as a rim of hyperintense signal in the myocardial delayed-enhancement sequences. The black-blood, triple IR, and bright-blood sequences were not diagnostic. Conclusion The diagnosis of EFE is difficult to establish by echocardiography. MRI using perfusion and myocardial delayed enhancement can be useful in establishing the diagnosis.