Elizabeth A Braunlin

University of Minnesota | UMN

Mucopolysaccharidosis type I (MPS I) is a rare metabolic disorder caused by deficiency of α-L-iduronidase (IDUA), resulting in glycosaminoglycan (GAG) accumulation and multisystemic disease. Current treatments include hematopoietic stem cell transplantation and enzyme replacement therapy, but these do not address all manifestations of the disease....

Mucopolysaccharidosis type I is an inborn error of glycosaminoglycan catabolism with phenotypes ranging from severe (Hurler syndrome) to attenuated (Hurler–Scheie and Scheie syndromes). Cardiovascular involvement is common and contributes significantly to morbidity and mortality. We conducted a retrospective analysis of the prevalence and natural h...

Novel therapies for Hurler syndrome aim to cross the blood‐brain barrier (BBB) to target neurodegeneration by degrading glycosaminoglycans (GAG). BBB penetration has been assumed with decreased cerebrospinal fluid (CSF) GAG, yet little is known about CSF GAG without brain‐targeting therapies. We compared pre‐transplant CSF GAG in patients who were...

Hunter syndrome, or mucopolysaccharidosis (MPS) II, is a rare lysosomal disorder characterized by progressive, multi-system disease. As most symptoms cannot be reversed once established, early detection and treatment prior to the onset of clinical symptoms are critical. However, it is difficult to identify affected individuals early in disease, and...

Introduction Biallelic damaging variants in ALPK3, encoding alpha-protein kinase 3, cause pediatric-onset cardiomyopathy with manifestations that are incompletely defined. Methods & Results We analyzed clinical manifestations of damaging biallelic ALPK3 variants in 19 pediatric patients, including nine previously published cases. Among these, 11 l...

The mammalian heart has a limited regenerative capacity and typically progresses to heart failure following injury. Here, we defined a hedgehog (HH)-Gli1-Mycn network for cardiomyocyte proliferation and heart regeneration from amphibians to mammals. Using a genome-wide screen, we verified that HH signaling was essential for heart regeneration in th...

BACKGROUND: High-dose aspirin (HDA) is used with intravenous immunoglobulin (IVIg) in Kawasaki Disease (KD). Practice regarding HDA varies, and it is unclear whether HDA duration affects long-term course. METHODS: We retrospectively studied KD patients at our hospital over 10 years. Patients were categorized as having received HDA for 0, 1–7, or >...

Background: Armed conflicts can result in humanitarian crises and have major impacts on civilians, of whom children represent a significant proportion. Usual pediatric medical care is often disrupted and trauma resulting from war-related injuries is often devastating. High pediatric mortality rates are thus experienced in these ravaged medical env...

Background and aim: Mucopolysaccharidosis IH (MPS IH, Hurler syndrome) naturally leads to death within the first decade of life, primarily from cardiac and pulmonary causes. To determine how hematopoietic stem cell transplantation (HSCT) has altered mortality, we analyzed our institution's 30-year experience of patients with MPS IH undergoing HSCT...

Mucopolysaccharidosis type I (MPS IH) is a lysosomal storage disease (LSD) caused by inactivating mutations to the alpha-L-iduronidase (IDUA) gene. Treatment focuses on IDUA enzyme replacement and currently employed methods can be non-uniform in their efficacy particularly for the cardiac and craniofacial pathology. Therefore, we undertook efforts...

Introduction: The mucopolysaccharidosis syndromes are a group of lethal inherited disorders affecting multiple organ systems by the progressive deposition of glycosaminoglycan. Advances in treatment such as enzyme replacement and hematopoietic stem cell transplantation have significantly improved the outcome of these disorders. An in-depth underst...

To evaluate the efficacy and safety of two dose levels of galsulfase (Naglazyme®) in infants with MPS VI. This was a phase 4, multicenter, multinational, open-label, two-dose level study. Subjects were randomized 1:1 to receive weekly infusions of 1.0 or 2.0 mg/kg of galsulfase for a minimum of 52 weeks. Progression of skeletal dysplasia was determ...

Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI (MPS VI). Cardiac ultrasound was performed to investigate these findings in subjects during long-term enzyme replacement therapy (ERT) with recombi-nant human arylsulfatase B (rhASB, rhN-acetylgalactosamin...

Background: Serious cardiac valve disease and left ventricular hypertrophy occur in most untreated older children with severe mucopolysaccharidosis type I. Although it is assumed that early intervention prevents these processes, evaluation of cardiac findings in these infants has not yet been reported. Methods: We reviewed echocardiograms of 13 unt...

This paper provides a detailed overview and discussion of anaesthesia in patients with mucopolysaccharidosis (MPS), the evaluation of risk factors in these patients and their anaesthetic management, including emergency airway issues. MPS represents a group of rare lysosomal storage disorders associated with an array of clinical manifestations. The...

Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI (MPS VI). Cardiac ultrasound was performed to investigate these findings in subjects during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB, rhN-acetylgalactosamine...

Mucopolysaccharidosis type IVA (MPS IVA) or Morquio syndrome is a multisystem disorder caused by galactosamine-6-sulfatase deficiency. Skeletal manifestations, including short stature, skeletal dysplasia, cervical instability, and joint destruction, are known to be associated with this condition. Due to the severity of these skeletal manifestations...

Background Although coronary artery pathology is a prominent feature of mucopolysaccharidosis (MPS), it may be underestimated by coronary angiography because of its diffuse nature. It is also generally assumed that cardiovascular risk is increased in MPS and reduced following hematopoietic stem cell transplantation (HSCT) or enzyme replacement ther...

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive inherited disease caused by deficiency of the glycosidase α-L-iduronidase (IDUA). Deficiency of IDUA leads to lysosomal accumulation of glycosaminoglycans (GAG) heparan and dermatan sulfate and associated multi-systemic disease, the most severe form of which is known as Hurler syndrome....

Background: Severe mucopolysaccharidosis type I (Hurler syndrome) is an autosomal recessive lysosomal storage disease of childhood that results in accumulation of glycosaminoglycans within cardiac valves and consequent valve dysfunction. Valve thickening in mucopolysaccharidosis type I (Hurler syndrome) is due, in part, to the presence of glycosam...

The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s...

The Jatene arterial switch operation (ASO) for dextro-transposition of the great arteries is ideally performed within the first 2 weeks of life. Clinical circumstances, however, may dictate a delayed ASO and left ventricle "retraining" prior to the procedure. Glucocorticoid remediable aldosteronism (GRA) accounts for 0.5% to 1% of primary aldostero...

Mechanical ventricular assistance has become a reliable tool for the support of children and infants with heart failure. The devices have shown efficacy both as a bridge to transplantation and as a bridge to recovery. The potential complications that may occur with long-term support have not been fully described. This article reports the occurrence...

The mitogen activated protein kinase (MAPK) signaling pathway regulates multiple events leading to heart failure including ventricular remodeling, contractility, hypertrophy, apoptosis, and fibrosis. The regulation of conserved intrinsic inhibitors of this pathway is poorly understood. We recently identified an up-regulation of Sprouty1 (Spry1) in...

Allogeneic transplantation remains the standard of care for patients with Hurler syndrome. As enzyme replacement therapy (ERT) has become available, controversy has emerged in regards to whether the use of enzyme in the peri-transplant period is appropriate. An analysis was performed on 74 patients with Hurler syndrome transplanted at the Universit...

Hurler syndrome (mucopolysaccharidosis type I/H; MPS I/H) is a lethal heritable enzymopathy that leads to an accumulation of glycosaminoglycans (GAGs) and dysfunction of multiple organs of the body, including the heart. As gender-related differences are common in heart disease and a murine model for mucopolysaccharidosis type I (MPSI) has been used...

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival factors in response to hypoxia and oxidative stress. We have previously shown that transplantation of Sca-1 ⁺ /CD31 ⁻ cells can improve LV function in hearts with acute myocardial infarction (AMI) although the engraftment rate was low. We hypothesiz...

Cellular therapy with non-hematopoietic adult stem cells (ASC) has emerged as a novel strategy for treatment of myocardial infarction (MI). Cells from non-identical donors, however, are typically rejected by the immune system of recipient. To overcome this barrier to transplantation we induced MI by left coronary artery ligation followed by direct...

Bone marrow-derived mononuclear cell (BMNC) transplantation provides the possibility of rescue or regeneration of myocardium lost during acute myocardial infarction (AMI). The extensive death of transplanted cells and the lack of sustained engraftment may limit its application. We investigated whether delivery of BMNCs by an injectable PEGylated fi...

Multipotent adult progenitor cells (MAPCs) are adult stem cells derived from bone marrow. We investigated the capacity of MAPCs to aid in tissue healing after myocardial ischemia in mice with different levels of immune competence. Adult murine C57BL/6 MAPCs were labeled with firefly luciferase and DsRed2 fluorescent protein and injected into the my...

Mucopolysaccharidosis type I is a lethal autosomal recessive storage disease caused by a deficiency of lysosomal alpha-L-iduronidase and the consequent systemic accumulation of glycosaminoglycan. Cardiomyopathy and valvar insufficiency occur as glycosaminoglycan accumulates in the myocardium, expands the spongiosa of cardiac valves, and proliferate...

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 o...

Allogeneic hematopoietic cell transplantation (HCT) continues to be standard therapy for patients with severe alpha-L-iduronidase deficiency, also termed Hurler syndrome. While many patients tolerate HCT well, in others severe toxicity is observed. An analysis was performed in 74 patients transplanted at the University of Minnesota for Hurler syndr...

I-cell disease or mucolipidosis type II, a rare inherited storage disorder of lysosomal enzyme localization, is characterized by dysostosis multiplex, progressive severe psychomotor retardation and death by 5-8 years from congestive heart failure and recurrent pulmonary infections. A 19-month old girl with I-cell disease received a bone marrow tran...

The Hurler syndrome, an autosomal recessive storage disease of childhood, leads to death within the first decade of life from progressive deposition of glycosaminoglycans within the myointima of the coronary arteries and airways. Cardiac ultrasound findings of patients with this syndrome >10 years after successful bone marrow transplantation are de...

The coronary arteries in a patient with the Hurler Syndrome appear only minimally affected by the deposition of glycosaminoglycans 14 years after successful bone marrow engraftment. This finding is added to the previously reported salutary effects of transplant on large airways, cardiac function, hepatic morphology, and central nervous system funct...

Open-lung biopsy is uncommon in children. Modern indications and outcomes are unknown. This is a retrospective review of 64 open-lung biopsies (58 patients) from 1976 to 1996. Open-lung biopsies were used to grade vasculopathy in 8 patients (12% of 64) with pulmonary hypertension and in 10 patients (16% of 64) with combined pulmonary hypertension a...

Endomyocardial biopsy remains the 'gold standard' for the diagnosis of acute rejection after cardiac transplantation, but few guidelines exist to determine the indications for its use in pediatric cardiac transplant recipients. To determine the usefulness of surveillance endomyocardial biopsy, 176 biopsies were reviewed from 12 patients, aged 0.5-1...

Endomyocardial biopsy remains the ‘gold standard’ for the diagnosis of acute rejection after cardiac transplantation, but few guidelines exist to determine the indications for its use in pediatric cardiac transplant recipients. To determine the usefulness of surveillance endomyocardial biopsy, 176 biopsies were reviewed from 12 patients, aged 0.5‐1...

To determine if cannulation of the internal jugular vein (IJV) with echocardiographic guidance increases the success and decreases the complications of the procedure when performed in children with heart disease. Twenty-five consecutive pediatric patients with heart disease who underwent IJV cannulation with echocardiographic guidance between Septe...

Severe coronary artery disease may occur early in the course of mucopolysaccharidosis. The authors present radiologic, scintigraphic, and pathologic findings in five patients with Hurler syndrome. Thallium-201 myocardial scintigraphy and selective coronary angiography obtained within 2 days to 6 months were correlated in five patients. Postmortem e...

Severe coronary artery disease may occur early in the course of mucopolysaccharidosis. The authors present radiologic, scintigraphic, and pathologic findings in five patients with Hurler syndrome. Thallium-201 myocardial scintigraphy and selective coronary angiography obtained within 2 days to 6 months were correlated in five patients. Postmortem e...

Cytomegalovirus colitis is one of the sequelae of cytomegalovirus infection in transplant patients and can be associated with severe consequences. This case details the clinical, radiographic, and laboratory features of this infection in a child after heart transplantation where early recognition and treatment resulted in complete resolution of the...

Pediatric heart transplantation has become an accepted method of treatment for certain pediatric heart disease. From July 1986 to January 1993, we performed 25 orthotopic pediatric heart transplantations at the University of Minnesota Hospital and Clinics in 16 male patients and nine female patients. The average age was 8.5 years with a range from...

Although pediatric cardiac transplantation has become a viable treatment modality, long-term follow-up of potential cardiac and noncardiac complications is limited. 1,2 Long-term electrocardiographic (ECG) changes in the adult transplant population have been investigated,3–5 but little is known regarding ECG findings after transplantation in childr...

The perioperative care, morbidity, and mortality in 30 patients with mucopolysaccharidosis (MPS) are presented. They underwent a detailed preoperative assessment and were anesthetized 141 times. An intravenous induction technique was used in most patients. It was easier to see the vocal cords, during laryngoscopy, in children with Hurler syndrome (...

Although heart, heart-lung, or lung transplantation is performed in more than 200 children annually, the number of patients referred for such procedures is considerably greater, and little is known about the outcome of those referrals. To determine the outcome of pediatric transplant referrals we reviewed the follow-up of 31 patients evaluated at o...

We studied 28 cardiac allografts (26 autopsied, 2 explanted) from 27 patients aged 4 to 57 years (mean 35 yr). The duration of transplant was 1 day to 6 yr (mean 13 months). A spectrum of pathology was seen in the whole hearts including chronic transplant vasculopathy (12 cases), acute cellular rejection (7 cases), fungal infection (4 cases), and E...

Although overall outcome has improved, pulmonary atresia with intact septum remains a difficult surgical and clinical problem. To determine whether an early right ventricular outflow patch will result in biventricular repair for this lesion, we reviewed the long-term follow-up (5.8 +/- 0.8 years) of 19 newborns who underwent repair between 1979 and...

Hurler syndrome (mucopolysaccharidosis type I-H) is an inherited lysosomal storage disease characterized by the widespread accumulation of mucopolysaccharide in tissues throughout the body.1 Although severe coronary artery luminal narrowing has been documented by postmortem examination of the heart of patients with Hurler syndrome,2 the only report...

Mechanical complications after heart transplantation are uncommon. We describe a case of hemodynamically significant suture line obstruction that was recognized immediately after heart transplantation using transesophageal echocardiography. Transesophageal echocardiography has proved to be a powerful tool in recognizing mechanical complications in...

Endomyocardial biopsy is said to be the gold standard for the diagnosis of cardiac rejection. In the pediatric age group endomyocardial biopsy is more difficult, and technically may be unsatisfactory. It is therefore desirable to correlate the biopsy finding with non-invasive studies so that patients may be monitored meaningfully, and endomyocardia...

The practice of pediatric cardiology has undergone remarkable changes over the past decade. Cardiac structural abnormalities may frequently be diagnosed with echocardiography alone, and treatment for many of these structural problems may be corrected during cardiac catheterization. Arrhythmia diagnosis and management have made similar progress, suc...

Although triple-drug immunosuppression (cyclosporine, azathioprine, and prednisone) has reduced the incidence of acute rejection after pediatric cardiac transplantation, its effect on the development of coronary artery disease, which may be the major determinant of long-term survival in these patients, is not well defined. We reviewed 42 coronary a...

Staged repair of interrupted aortic arch and ventricular septal defect was carried out in 20 infants from 1979 through 1990. Among the important associated cardiac defects were transposition of the great arteries, truncus arteriosus, and anomalous origin of the right pulmonary artery. The first stage, usually consisting of the placement of an 8- or...

Although triple-drug immunosuppression with a combination of cyclosporine, prednisone, and azathioprine has been shown to improve short-term survival after cardiac transplantation, its long-term effects still are unknown. From December 1983 through December 1988, all patients (N = 139) who underwent orthotopic cardiac transplant at our institution...

Cardiac transplantation has only recently become an accepted therapeutic modality for children and adolescents with end-stage cardiomyopathy. Long-term survival, the incidence of rejection, and the incidence of infection are still being defined. From 1985 to 1989, 21 children aged 6 months to 19 years (average age, 11.2 years) underwent cardiac tra...