Divergent clinical outcomes of alpha-glucosidase enzyme replacement therapy in two siblings with infantile-onset Pompe disease treated in the symptomatic or pre-symptomatic state.

Pompe disease is an autosomal recessive, lysosomal glycogen storage disease caused by acid α-glucosidase deficiency. Infantile-onset Pompe disease (IOPD) is the most severe form and is characterized by cardiomyopathy, respiratory distress, hepatomegaly, and skeletal muscle weakness. Untreated, IOPD generally results in death within the first year of life. Enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has been shown to markedly improve the life expectancy of patients with IOPD. However, the efficacy of ERT in patients with IOPD is affected by the presence of symptoms and cross-reactive immunologic material (CRIM) status. We have treated two siblings with IOPD with ERT at different ages: the first was symptomatic and the second was asymptomatic. The female proband (Patient 1) was diagnosed with IOPD and initiated ERT at 4 months of age. Her younger sister (Patient 2) was diagnosed with IOPD at 10 days of age and initiated ERT at Day 12. Patient 1, now 6 years old, is alive but bedridden, and requires 24-hour invasive ventilation due to gradually progressive muscle weakness. In Patient 2, typical symptoms of IOPD, including cardiac failure, respiratory distress, progressive muscle weakness, hepatomegaly and myopathic facial features were largely absent during the first 12 months of ERT. Her cardiac function and mobility were well-maintained for the first 3 years, and she had normal motor development. However, she developed progressive hearing impairment and muscle weakness after 3 years of ERT. Both siblings have had low anti-rhGAA immunoglobulin G (IgG) antibody titers during ERT and have tolerated the treatment well. These results suggest that initiation of ERT during the pre-symptomatic period can prevent and/or attenuate the progression of IOPD, including cardiomyopathy, respiratory distress, and muscle weakness for first several years of ERT. However, to improve the long-term efficacy of ERT for IOPD, new strategies for ERT for IOPD, e.g. modifying the enzyme to enhance uptake into skeletal muscle and/or to cross the blood brain barrier (BBB), will be required.

An infant with primary pulmonary vein stenosis, associated with fatal occlusion of intraparenchymal small pulmonary veins.

Primary pulmonary vein stenosis (PVS) is rare within the pediatric population and its pathophysiology remains unclear, especially as to how the histopathology relates to its refractoriness to treatment. We report the case of a 4-month-old girl with primary PVS. The lesion in this patient was characterized by fatal obstruction of intraparenchymal small pulmonary veins, associated with localized stenosis at the four pulmonary veno-atrial junctions. All four localized stenoses underwent transcatheter stent implantation. Although the procedure was technically successful, her clinical status failed to improve, and she died 2 months after stenting. Histopathological examination of lung specimens showed severe luminal obstruction by marked intimal proliferation with fibrosis in the intraparenchymal small pulmonary veins, and these findings were present in every lobe. To the best of our knowledge, the histopathological findings and clinical course in this case, including the response to treatments, are extremely rare. We suggest that the histological findings of the small pulmonary veins are important in deciding the indication and appropriate timing of intervention. .

Restored left ventricular function following transcatheter closure of a persistent ductus arteriosus in an adult.

Recently, transcatheter device occlusion has become the first choice treatment for adult persistent ductus arteriosus (PDA). However, various complications such as atrial fibrillation requiring anticoagulation, pulmonary hypertension, and ventricular dysfunction may challenge the interventionist. We report a 61-year-old patient with a large PDA complicated by left ventricular dysfunction, atrial fibrillation, and left atrial thrombus. Computed tomography documented the PDA of Krichenko type A with the narrowest diameter of 8 mm. We successfully closed the PDA using an Amplatzer duct occluder under anticoagulation with wafarin. His post-operative course was complicated by ventricular tachycardia and deteriorating left ventricular pump function. Although endomyocardial biopsy from the left ventricle showed myocardial hypertrophy and interstitial fibrosis, possibly caused by chronic volume overload, left ventricular pump function improved dramatically with restoration of sinus rhythm during follow-up. Left ventricular dysfunction, even when associated with histological changes, may be nearly normalized by volume unloading in an adult with a large PDA. .

Coil occlusion of PDA in patients younger than 1 year: risk factors for adverse events.

BACKGROUND: Transcatheter occlusion of infantile patent ductus arteriosus (PDA) challenges the interventionist. PURPOSE: To analyze the risk factors for adverse events from this procedure in patients younger than 12 months. SUBJECTS: We retrospectively analyzed data on 32 patients younger than 12 months in whom transcatheter coil occlusion of a PDA was attempted. Ages ranged from 1 to 11 (median, 7) months and body weight from 1.2 to 10 (6.0) kg. The minimum ductal diameter ranged from 1.0 to 4.6 (3.3) mm and pulmonary to systemic flow ratio from 0.7 to 12.5 (2.2). Major adverse events were defined as those requiring surgery, while minor adverse events included transient hemolysis not needing treatment, coil migration with successful transcatheter retrieval, and mild left pulmonary artery (PA) stenosis. We determined whether any factors such as age, body weight, minimum PDA diameter, angiographic type, operator, and use of a 0.052-in. Gianturco coil related to the occurrence of adverse events. RESULTS: In two patients, coils could not be deployed in the appropriate position. They underwent surgery following transcatheter retrieval of coils. Coils were successfully deployed in the other 30 patients, however, one patient developed persistent hemolysis that required surgical retrieval of the coils and closure. PDA was completely closed in the other 29 patients (clinical success rate, 91%). Thus, there were three major adverse events, while minor adverse events occurred in five patients. Univariate analysis did not identify any single factor that contributed to either major, minor, or total adverse events. However, all major adverse events occurred in patients under 6 months and less than 6 kg body weight with a minimum duct diameter of more than 3.5 mm. CONCLUSION: Transcatheter coil occlusion of PDA is feasible in selected patients younger than 1 year. A minimum diameter more than 3.5 mm in patients under 6 kg may be a risk factor for major adverse events.

Stenting of a stenosed major aortopulmonary collateral artery in a baby with pulmonary atresia and a ventricular septal defect: rescue from critical hypoxia in the immediate postoperative stage of unifocalization supported by extracorporeal membrane oxygenation.

A 4-month baby with pulmonary atresia, ventricular septal defect, major aortopulmonary collateral arteries (MAPCAs) and an extremely hypoplastic central pulmonary artery developed critical hypoxia following right unifocalization combined with a right Blalock-Taussig shunt. To increase pulmonary blood flow we stented the left lower MAPCA during extracorporeal membrane oxygenation (ECMO) support. He was successfully weaned from ECMO 2 days after stenting. Percutaneous intervention for a stenosed MAPCA is an effective means of increasing pulmonary blood flow in critically hypoxic patients following unilateral unifocalization, even in the immediate postoperative stage.

[Cardiovascular and the other complication followed with Kawasaki disease].

Kawasaki disease (KD) was considered to be good prognosis in self-limited at first. But, sudden death followed KD has been reported. It became clear that KD produce the peculiar state of myocardial infarction in infants and young children. Now, KD took the place of the rheumatic fever and got the most important disease of acquired heart disease in childhood. Cardiovascular disorder is mainly included with the coronary arterial aneurysm. And aneurysm in an subaxial and iliac artery were complicated. Every organ flame in a whole body was produced with systematic vasculitis mainly on a medium size or small size artery of a whole body. We summarize about complications of a cardiovascular system and the other organs followed KD.

[Action on care and management of adult patients with a history of Kawasaki disease].

Based on the nationwide database of Japan in January 2006, a cumulative number of the patients exceeded 200,000, while 90,000 patients are now older than 20 years old. The Japan Kawasaki Disease Committee established the guideline of its management in 2002. In adult patients with coronary sequelae, there is no doubt on the necessity of life-long-follow-up, while there is still arguments on how do we care the adult patients with no or mild coronary involvements in the acute phase which regressed spontaneously. The coronary artery sequelae of Kawasaki disease may be an important cause of ischemic heart disease in young adults, particularly under 40 years of age. In this review, we discuss how we care adult patients with a history of Kawasaki disease with coronary sequelae. Finally, we recommend opening the outpatient office for adult patients with a history of Kawasaki disease, because the frequency where adult patients followed Kawasaki disease stops consulting a medical institution became high.

A polymorphism in plasma platelet-activating factor acetylhydrolase is involved in resistance to immunoglobulin treatment in Kawasaki disease.

OBJECTIVE: To investigate whether reduced levels of plasma platelet-activating factor acetylhydrolase (PAF-AH) as a result of a genetic polymorphism are involved in the pathogenesis of Kawasaki disease (KD). STUDY DESIGN: The frequency of a V279F polymorphism (G/T transversion) in the PAF-AH gene was quantified in 76 Japanese children with KD and 112 healthy Japanese adults using the allele-specific polymerase chain reaction (PCR). Associations between genotype, clinical features, and resistance to intravenous immunoglobulin (IVIG) were investigated in the patients with KD. Plasma PAF-AH activity was measured by using [3H]-acetyl-PAF. RESULTS: There were no significant differences in genotype frequency between patients and controls (P = .51). Compared with the GG (normal genotype) group, significantly more patients in the GT (heterozygous) +TT (homozygous deficient) group required additional IVIG (52% vs 14%, P = .001). The duration of fever and maximum serum C-reactive protein (CRP) levels also were significantly increased in the GT+TT group (P = .012 and .036, respectively), whereas plasma PAF-AH activity was significantly lower (P <.0001). CONCLUSION: We conclude that the V279F polymorphism in the plasma PAF-AH gene and consequent enzymatic deficiency is one of the factors for IVIG nonresponse in Japanese patients with acute KD.

Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition).

Diagnostic guidelines for Kawasaki Disease was revised to meet the present situation in 2002. This issue intends to explain new guidelines and their backgrounds. Major alterations are interpretation of cases with 4 or fewer febrile days shortened by early intravenous immunoglobulin treatment, and the clinical importance of atypical (incomplete, or suspected) cases.

Differences in growth characteristics and dynamics of elements absorbed in seedlings of three spruce species raised on serpentine soil in northern Japan.

BACKGROUND AND AIMS: Serpentine soils are characterized by the presence of heavy metals (Ni and Cr) and excess Mg; these elements often suppress plant growth. Picea glehnii is nevertheless distributed widely on serpentine soils in northern Japan. Growth characteristics were compared among P. glehnii, Picea jezoensis (distributed in the same region) and Picea abies (planted for timber production), and concentrations of elements in various tissues over time and the amount of ectomycorrhizal infection in short roots were evaluated. METHODS: Seedlings of three spruce species were planted in two types of experimental plots, comprising serpentine soil and brown forest (non-serpentine) soil, and these seedlings were grown for 3 years. Growth, ectomycorrhizal infection of short roots, and elemental composition of tissues were examined. KEY RESULTS: The total dry mass of P. glehnii planted on serpentine soil was almost the same as on brown forest soil, and a large number of needles survived to reach later age classes. By contrast, growth of P. jezoensis and P. abies in serpentine soil was significantly less than in brown forest soil, and needle shedding was accelerated. Moreover, roots of seedlings of P. glehnii on serpentine soil were highly infected with ectomycorrhiza, and the concentration of Ni in needles and roots of P. glehnii was the lowest of the three species. CONCLUSIONS: Picea glehnii has a high ability to maintain a low concentration of Ni, and the ectomycorrhizal infection may have the positive effect of excluding Ni. As a result, P. glehnii is more tolerant than the other spruce species to serpentine soil conditions.

Evaluation of the inferior vena cava in potential pediatric renal transplant recipients.

Vascular anomalies due to occlusion or thrombosis of the inferior vena cava (IVC) may be hazardous to renal transplantation, and preoperative vascular evaluation is important for safe and successful surgery. The purpose of this study was to assess the utility and accuracy of two-dimensional time-of-flight (2D-TOF) magnetic resonance venography (MRV) as an alternative to conventional angiography for evaluating the IVC and iliac vein in potential pediatric renal transplant recipients. Four children with chronic renal failure were evaluated with 2D-TOF MRV by superior presaturation pulse and target maximum intensity projection. The whole MRV examination and filming required less than 30 min. All four patients had a normal IVC and iliac vein. Two of the patients underwent renal transplantation, and the MRV findings were in total agreement with the final anatomy revealed intraoperatively. MRV is accurate for evaluating the condition of the IVC and iliac vein. It is a reliable, noninvasive and rapid technique that can be considered as an alternative to invasive angiography for evaluation of children scheduled for transplantation. We recommend the use of this noninvasive procedure to ascertain the patency of the IVC in all infants and children with a history of indwelling catheters in the IVC or those with a propensity to thrombosis, i.e., all recipients with nephrotic syndrome. The insertion of catheters in the femoral vein in children who may become candidates for renal transplantation should be discouraged.

Water retention in the acute phase of Kawasaki disease: relationship between oedema and the development of coronary arterial lesions.

UNLABELLED: Despite intravenous immunoglobulin therapy, a certain percentage of patients with Kawasaki disease (KD) still develop coronary arterial lesions (CAL). In an effort to find new combined therapies to reduce the incidence of CAL, we focused on the oedema which can be an important sign of the increased vascular permeability in KD. A total of 127 patients with KD were included in the retrospective study. Serial weekly changes in serum sodium and albumin levels from the 1st to the 4th week of illness were examined. In addition, the maximum rate of increase in body weight from admission to the 14th day of illness was evaluated. Serum sodium levels (mEq/l) in only the 2nd week of illness were significantly lower in patients with CAL than in those without CAL (mean +/- SD, 135.5+/-4.5 versus 138.0+/-2.4, P<0.05). Serum albumin levels in all 4 weeks were significantly lower in patients with CAL than in those without CAL ( P<0.001). The maximum rate (%) of increase in body weight from admission to the 14th day of illness was significantly higher in patients with CAL than in those without CAL (ranges and median values, 0-12.3 (7.0) versus 0-10.3 (3.2), P<0.001). CONCLUSION: these results suggest that water retention in the acute phase of Kawasaki disease may be a risk factor for CAL, and water intake of both infusion and oral intake should be kept to a minimum in order to avoid progressive oedema.

Detection of auto-antibodies against a 70 kDa protein derived from vascular smooth muscle cells in patients with Kawasaki disease.

UNLABELLED: The aetiology and pathogenesis of Kawasaki disease (KD) remain unknown. To investigate the pathogenesis of vasculitis in KD, we tested for the presence of auto-antibodies against a component of vascular smooth muscle cells in the sera of patients with KD. Sera from 48 patients with KD, as well as sera from 14 sick children and from 22 healthy children, were examined for reactivity to both coronary arterial wall tissues and cultured smooth muscle cells (CSMC) derived from human coronary artery, using immunofluorescence and Western immunoblot assay techniques. Sera from 16 of 48 patients with KD gave positive immunoreactions to the vascular walls of coronary artery with fluorescein isothiocyanate-labelled rabbit anti-human IgA antibodies. In Western immunoblot assays, the sera from 15 of 34 and 10 of 31 patients with KD showed positive reactions against a 70 kDa protein from CSMC with IgA and IgM antibodies, respectively. Positive immunoreactivity of sera from patients with KD, determined either by immunofluorescence studies or by Western immunoblotting, was detected more frequently ( P<0.05) and more intensely ( P<0.005) in patients with coronary arterial lesions (CAL) than in those without CAL. Positive immunoreactivity of sera was prominent before intravenous immunoglobulin therapy and decreased dramatically thereafter. CONCLUSION: these data suggest that auto-antibodies against a 70 kDa protein from vascular smooth muscle cells may cause coronary arteritis and systemic vasculitis in KD.