Diagnosis Of Hurler Syndrome Research Articles

Mucopolysaccharidosis Type I, Hematopoietic Cell Transplantation and Neurodevelopmental Profile: A Case Report

Type I mucopolysaccharidosis is caused by an alpha-L-iduronidase deficit and has three phenotypic expressions. Hurler syndrome includes dysmorphias, hirsutism, hepatosplenomegaly, hydrocephalus, skeletal deformities, recurrent infections, heart abnormalities, and global developmental delay. Hematopoietic cell transplantation provides a continuous source of alpha-L-iduronidase throughout the body, including the central nervous system and, currently, appears to be the gold-standard therapy for this pathology. We present the case of a six-years-old child with the diagnosis of Hurler syndrome, submitted to hematopoietic cell transplantation and integrated in a structured support plan with special education, speech therapy and early home intervention, who presents a trend of convergence with the normality in all the development areas, except for locomotor skills and eye-hand coordination. These findings highlight the positive impact of the hematopoietic cell transplantation together with the early and structured intervention of a multidisciplinary team in the neurodevelopmental profile of children affected by Hurler syndrome.

Case Report: Hurler syndrome (Mucopolysaccharidosis Type 1) in a young female patient

Hurler syndrome is a rare autosomal recessive disorder of mucopolysaccharide metabolism. Here, we present the case of a young female patient who presented with features of respiratory distress. In addition, the patient had gingival hypertrophy, spaced dentition, misaligned eruptive permanent dentition, microdontia, coarse facial features, low set ears, depressed nasal bridge, distended abdomen, pectus carinatum, umbilical hernia and J-shaped Sella Turcica on an X-ray of the skull. A diagnosis of Hurler syndrome (Mucopolysaccharidosis Type I) was made. The patient was kept on ventilator support from the third day; however, she died on the fifth day of admission. Enzyme replacement modality of treatment can increase a patient's survival rate if an early diagnosis can be made. To the best of our knowledge, only a few cases of Hurler syndrome have been reported in Pakistan.

The Changing Patterns of Graft Failure in MPS1H, Hurler Syndrome: A Review of 30-Years Experience

Introduction: Hurler syndrome (HS), the most severe phenotype of mucopolysaccharidosis type I, is characterized by α-L-iduronidase (IDUA) deficiency. Without therapy, most affected children die of cardiac complications in the first decade. Haematopoietic stem cell transplantation (HSCT) is the standard of care in children with HS as it is the only therapy that can arrest disease progression. One of the challenges in HSCT for HS is graft failure. Here, we examined the evolving pattern of graft failure over the past three decades.Methods: Retrospective review of all children with HS undergoing first HSCT at the Royal Manchester Children’s Hospital or the University of Minnesota Children’s Hospital over a thirty-four-year period (1983 - 2016). The diagnosis of HS was confirmed by an increase in urinary GAG excretion, a deficiency or absence of IDUA in peripheral blood leukocytes, and the clinical phenotype. A full-intensity Busulfan-based myeloablative conditioning regimen (MAC) with pharmacokinetic-guided dosing was started from 2004 (post Bu-pK era). Conditioning regimen used prior to Bu-pK era was variable. Graft failure was classified into 4 types: 1. Primary aplasia, (no neutrophil engraftment by Day +42) 2. Primary autologous reconstitution (neutrophil engrafted by Day +42 but with <20% donor-derived hematopoiesis) 3. Secondary aplasia (cytopenia following neutrophil engraftment and fully donor-derived hematopoiesis) 4. Secondary autologous reconstitution (falling donor chimerism <20% following neutrophil engraftment and adequate donor-derived hematopoeisis)Results: A total of 240 children with HS were enrolled (131 pre-Bu-pK; 109 post-Bu-pK). The median age at HSCT was 16.3 months (range 4.9-72.2 months) in pre-Bu-pK era and 14.0 months (range 3.8-65.1 months) in post-Bu-pK era (p = 0.002) ). In pre-Bu-pK era, the graft source was predominately marrow/peripheral blood (n=109, 83.2%). The use of cord blood (CB) increased from 16.8% (n=22) in pre-Bu-pk era to 63.3% (n=69) in post-Bu-pK era (p<0.001). The 5-year overall survival (OS) improved from 60.8% to 85.2% (p<0.001) while the 5-year event-free survival increased from 41.2% to 76.3% (p<0.01) in the modern era. The proportion of patients with graft failure reduced significantly from 37.2% (49/113 patients) in pre-Bu-pK era to 10.1% (11/109 patients) in post-Bu-pK era (p<0.001). Of the 49 patients with graft failure in pre-Bu-pK era, 1 had primary aplasia, 19 had primary autologous reconstitution and 28 had secondary autologous reconstitution. In the post-Bu-pk era, all the graft failure occurred in CB recipients (10 had a busulfan based MAC; 1 had a non-MAC). Of these 11 patients, 7 patients had aplasia while 4 had autologous marrow reconstitution. On univariate analysis, neither pre-transplant factors (age and sex) nor transplant factors (graft-recipient HLA disparity, total nucleated cell dose, CD34+ cell dose, graft-recipient ABO compatibility, conditioning regimen, type of serotherapy and GVHD prophylaxis regimen) were correlated with graft failure in CB recipients receiving busulfan-based MAC in the post-Bu-pK era. Of 60 patients with graft failure, 48 (39 pre-Bu-pK; 9 post-Bu-pK) had a second transplant. Of the 39 patients undergoing second transplant in the early era, 13 died and 5 had repeat graft failure. Three patients underwent third transplant and all died of transplant-related complications (1 GVHD, 2 infection). Of the 9 patients undergoing second transplant in the modern era, 8 are alive and engrafted; the sole death was from adenoviral infection. For all patients undergoing second HSCT, the estimated 5-year OS 70.1% (pre-Bu-pK 66.7% vs. post-Bu-pK 85.7%, p=0.235). Of the 85 patients who were "alive-and-engrafted" after first transplant in post-Bu-pK era, 68 (80%) had full-donor chimerism while 17 (20%) had mixed-donor chimerism. CB was significantly associated with a higher rate of full-donor chimerism (p=0.01) among engrafted survivors.Conclusions: The transplant outcomes have improved. All deaths due to infection, graft failure and pulmonary failure have significantly reduced a better transplant care. The pattern of graft failure has changed from primarily marrow reconstitution likely secondary to inadequate myelosuppression in pre-Bu-pk era, to graft rejection likely secondary to inadequate immunosuppression in post-Bu-pk era. DisclosuresJones:Genzyme: Consultancy, Research Funding, Speakers Bureau; BioMarin: Consultancy, Research Funding, Speakers Bureau.

Total Hip Arthroplasty in Mucopolysaccharidosis Type IH

Children affected by mucopolysaccharidosis (MPS) type IH (Hurler Syndrome), an autosomal recessive metabolic disorder, are known to experience a range of musculoskeletal manifestations including spinal abnormalities, hand abnormalities, generalised joint stiffness, genu valgum, and hip dysplasia and avascular necrosis. Enzyme therapy, in the form of bone marrow transplantation, significantly increases life expectancy but does not prevent the development of the associated musculoskeletal disorders. We present the case of a 23-year-old woman with a diagnosis of Hurler syndrome with a satisfactory result following uncemented total hip arthroplasty.

Prenatal diagnosis of the Hurler syndrome by microsatellite markers analysis

Summary Hurler's syndrome or mucopolysaccharidosis type IH (MPS IH) is the most severe form of mucopolysaccharidosis type I (MPS I). It is caused by the deficiency of the alpha- l -iduronidase (IDUA) activity. The accumulation of undegraded MPS affects various organs and tissues. Prenatal diagnosis MPS IH is possible on both cultured amniotic fluid cells and chorionic villus biopsies and it is preferably achieved by the assay of IDUA in uncultured chorionic villus as this allows early (12th week), rapid (2–3 days) and reliable results. Aim of the study We summarise the results of antenatal diagnosis in a woman of 36-year-old which has previously tow children affected by Hurler disease. Patients and methods Molecular analysis confirmed the diagnosis for the MPS I studied families. Sequencing of the DNA and multiplex fluorescent PCR were employed for mutation analysis, contamination detection and diagnosis of Hurler syndrome. Results Sequencing of genomic DNA extracted from trophoblaste and the two parents showed the heterozygous status of p.F602X. Microsatellite markers study confirmed the sequencing results and showed the absence of contamination of the foetal DNA by maternal DNA. Conclusion The molecular prenatal diagnosis is now easy and helps some Tunisian family to detect and identify the inherited fetal alleles.

Hurler syndrome with a tuft of hair

A 2-year-old girl presented with coarse, thick hairy skin all over the body, a tuft of hair in the parietal region, coarse facial features and a prominent forehead with a large tongue, hepatosplenomegaly and skeletal deformities. Mucopolysaccharides excretion spot test of the urine was positive; and an assay for glycosaminoglycans in the urine was also high, which confirmed the clinical diagnosis of Hurler syndrome. We present this rare case to discuss the possibility of the association of mental retardation with a tuft of hair in this syndrome.

Early Diagnosis of Hurler's Syndrome with the Aid of the Identification of the Characteristic Gibbus Deformity

This case study describes the clinical evaluation and diagnosis of Hurler's syndrome in a 7-month-old child who was noted to have a thoracolumbar kyphosis (gibbus deformity), coarse facial features, and possible evidence of gross motor delay. The diagnosis of Hurler's syndrome was aided specifically by the identification of the gibbus deformity. Children with Hurler's syndrome appear nearly normal at birth, and the most common early presenting features are the nonspecific symptoms of rhinitis and inguinal hernia. Most often, the earliest possible diagnosis of Hurler's syndrome is contingent on the recognition of the initial pattern of musculoskeletal abnormalities, which become increasingly pronounced after the 6th month. Because of the characteristic progression of neurological and intellectual deterioration found in children with Hurler's syndrome, early diagnosis and treatment are critical to the preservation of long-term intellectual development. The pathophysiology of Hurler's syndrome and the causes of kyphosis in infancy and childhood are discussed.