Body Height of MPS I and II Patients after Hematopoietic Stem Cell Transplantation: The Impact of Dermatan Sulphate.

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) comprises one of the two main treatment regimens for patients with mucopolysaccharidoses (MPS). There is a scarcity of literature concerning the process of growth in children with Mucopolysaccharidosis type I (MPS I) and Mucopolysaccharidosis type I (MPS II) after HSCT. The aim of this manuscript was to evaluate the therapeutic effect of HSCT on the heights of patients with MPS I and MPS II. MATERIAL AND METHODS: It was an observational, single-center study on patients with MPS I and II treated with HSCT. RESULTS: 6 MPS patients, including 4 MPS I and 2 MPS II, underwent HSCT at a median age of 2 years. All patients are alive to date, with a median age of 7.7 years (range 5.5-12 years) at the last follow-up. In both (MPS I and MPS II) groups of patients treated with HSCT, the growth rate was higher than in untreated patients and was found to be in line with the population norm. In both MPS I and MPS II patients who were treated with HSCT, normalization of urinary GAG excretion was observed. Additionally, no bands of DS and HS in GAG electrophoresis were visible. CONCLUSIONS: Both MPS I and MPS II patients presented height gain after HSCT compared to the curves of untreated patients. The absence of dermatan sulphate after HSCT could lead to normal growth in bone length.

Restricted joint range of motion in patients with MPS II: correlation with height, age and functional status.

AIM: The aims of the study were to assess shoulder range of motion (ROM) in patients with mucopolysaccharidosis type II (MPS II) and to correlate joint mobility with patients' height, age and functional status. METHODS: Passive ROM and Z-score of height were followed in 29 patients with MPS II (mean age 11.5 years, range 2-29 years) between the years 2005 and 2010. Passive ROM was measured by a goniometer, and height, by a stadiometer. Functional status was assessed by an age-appropriate health assessment questionnaire (HAQ). RESULTS: (i) A strong correlation was observed between patients' age and Z-score of patients' height (R = 0.78, p < 0.001). (ii) A medium correlation was observed between Z-score of patients' height and passive shoulder flexion and abduction (R = 0.697, p < 0.001 and R = 0.63, p < 0.001, respectively). The progression of restriction was slower in attenuated patients. (iii) Restrictions in shoulder flexion and abduction were already observed before the second year of life. (iv) ROM limitations intensified and became more severe with age. (v) Activities of daily living depended on cognitive impairment of patients with MPS II. CONCLUSION: Range of motion limitations in patients with MPS II correlate with patients' height, increase with patients' age and are more pronounced in a severe form of MPS II.

Spinal cord compression in Maroteaux-Lamy syndrome: case report and review of the literature with effects of enzyme replacement therapy.

UNLABELLED: The purpose of this report is to review the literature regarding spinal cord compression in mucopolysaccharidosis type VI (MPS VI), to discuss the possible impact of enzyme replacement therapy (ERT) and to stress the necessity of timely surgical intervention. A 9.5-year-old female patient with severe MPS VI had been receiving ERT since the age of 7. After 2.5 years of treatment, she developed craniovertebral canal stenosis with spinal cord compression and cervical myelopathy. CONCLUSIONS: (1) baseline cervical spine evaluation and regular neurological assessment should be performed in all MPS VI patients, (2) detailed neurological observation should be conducted in patients treated with ERT, especially in the period of improvement in the osteoarticular system, as ERT fails to prevent cervical myelopathy and (3) surgical decompression is required and in order to achieve a satisfying outcome it might be crucial to perform surgery at an early age.

Efficacy of Enzyme Replacement Therapy on the range of motion of the upper and lower extremities in 16 Polish patients with mucopolysaccharidosis type II: A long-term follow-up study.

BACKGROUND: Enzyme replacement therapy (ERT) with idursulfase is available for patients with mucopolysaccharidosis (MPS) type II, and improvements in certain somatic signs and symptoms have been reported. The aim of the study was to assess the effectiveness of ERT with idursulfase (Elaprase®) on the passive joint range of motion (JROM) in the upper and lower extremities of patients with MPS II. METHODS: The study included 16 Polish patients diagnosed with MPS II and followed in our Institute in the years 2009-2016. The study group was divided for groups of neuronopathic (group 1, n=12) and non-neuronopathic (group 2, n=4) patients. A passive JROM was measured with a goniometer by one physiotherapist, while in group 1 it was assessed at baseline and after both short-term (52 weeks) and long-term (mean 230 weeks, range: 108-332 weeks) ERT. In group 2, it was assessed at baseline and after short-term ERT (68-85 weeks, no data for long-term ERT). RESULTS: In group 1, after 52 weeks of ERT, we observed some improvement of passive ROM in wrist flexion (5/12 patients), shoulder abduction and wrist extension (3/12 patients), shoulder flexion, elbow and knee extension (2/12 patients). After long-term ERT (mean 230 weeks), the improvement in JROM was observed only in 2 patients. There was no improvement in the shoulder abduction, elbow flexion and extension, hip and knee extension. In group 2, the improvement in passive ROM was observed in several joints: shoulder flexion, wrist flexion and extension improved (2/4 patients) and shoulder abduction (1/4 patients). CONCLUSION: ERT is of low efficacy on correcting the range of motion of joints in MPS II patients.

Improvement in the range of joint motion in seven patients with mucopolysaccharidosis type II during experimental gene expression-targeted isoflavone therapy (GET IT).

Mucopolysaccharidosis type II (MPS II, Hunter disease) is an X chromosome-linked inherited metabolic disease caused by mutations resulting in deficiency of activity of iduronate-2-sulfatase (IDS) and accumulation of undegraded glycosaminoglycans (GAGs), heparan sulfate, and dermatan sulfate. Previous experiments with cell cultures and studies on animal model of MPS II suggested that gene expression-targeted isoflavone therapy (GET IT), based on genistein-mediated reduction of efficiency of GAG synthesis, might be a suitable therapy for this disease. In this report, we demonstrate efficacy of GET IT in connective tissue elasticity, particularly in improving the range of joint motion in seven patients with MPS II after 26 weeks of treatment with an isoflavone extract at the dose corresponding to 5 mg/kg/day of genistein.

Anthropometric data of 14 patients with mucopolysaccharidosis I: retrospective analysis and efficacy of recombinant human alpha-L-iduronidase (laronidase).

OBJECTIVES: Our goal was to evaluate growth patterns in terms of body height, weight, head and chest circumference in patients with mucopolysaccharidosis type I (MPS I) without treatment and after enzyme replacement therapy (ERT) with alpha-l-iduronidase (laronidase). PATIENTS AND METHODS: Anthropometric features of 14 patients with MPS I were followed from birth until the introduction of ERT (group 1-1st year of life, group 2 3rd year of life), after 52-260 weeks of ERT and periodically during treatment. The data since birth until beginning of treatment was obtained by retrospective review of patients' charts. Patients received intravenous laronidase at 100 U/kg (0.58 mg/kg) weekly for 52-260 weeks. RESULTS: Patients from group 1 (n=7) and group 2 (n=7) had similar characteristics at the time of birth but showed significant difference when compared with healthy population. Growth patterns were associated significantly with the MPS I at birth. After 96-260 weeks of ERT, patients receiving laronidase (group 1) compared with group 2 did not show statistically significant improvement. CONCLUSIONS: Anthropometric features of patients with MPS I significantly differ from the healthy population. Children with MPS I grew considerably slower, and differences between healthy and affected children increased with age. In studied patients with MPS I, laronidase did not appear to alter the growth patterns.

Efficacy of recombinant human alpha-L-iduronidase (laronidase) on restricted range of motion of upper extremities in mucopolysaccharidosis type I patients.

The aims of the study were to assess the effectiveness of enzyme replacement therapy (ERT) with laronidase on the range of motion (ROM) of upper extremities and influence on activities of daily living (ADLs) of patients with mucopolysaccharidosis type I (MPS I). The ROM of 17 patients with MPS I was followed from the first year of life until the introduction of ERT and after 52-208 weeks of treatment. In all patients (group 1, n = 10), passive ROM was assessed. In patients with Hurler/Scheie or Scheie phenotype (group 2, n = 7) both passive and active ROM, as well as daily life activities, were evaluated. Passive and active ROM was measured by a goniometer, while a health assessment questionnaire was used to assess activities of daily living. The data since the first months of life until the beginning of treatment were obtained by retrospective review of patients' charts. Restriction in ROM of the upper extremities of patients with MPS I was observed from the first year of life. These limitations intensified and became more severe with the patients' age, making patients' self-care more difficult or even impossible. Introduction of ERT led to slower progression of symptoms, especially in the passive range of motion in all patients. Additionally, patients with normal mental development, or only slightly delayed (group 2), who underwent active physical rehabilitation (including mobilisation of nerve system, passive techniques for joint mobility, active gymnastics for muscle power, as well as massage and the training of families for therapy at home) showed improvement in active movement followed by enhanced self-care.

Modeling Morquio A Syndrome: An Anthropometric Study of Body Characteristics and Stature.

BACKGROUND: Morquio A syndrome or mucopolysaccharidosis (MPS) IVA is an autosomal recessive, life-limiting lysosomal storage disease caused by deficient activity of the enzyme galactosamine-6-sulfatase. Common early symptoms such as abnormalities of body stature can facilitate timely diagnosis. This study aimed to create a pattern of face and body stature based on anthropometric measurements taken from a cohort of Polish patients with MPS IVA. METHODS: Analysis of 11 somatometric and 14 craniofacial features was performed on 20 patients with MPS IVA, aged from 3 months to 26 years. The diagnosis of MPS IVA was confirmed by enzymatic and molecular analysis. Two-tailed t-tests were used to compare mean values for body length and weight at birth between the MPS IVA patients and the general population. To show the degree and direction of deviation z-scores were calculated and then used to construct a model of an average MPS IVA patient. RESULTS: Mean values for body height and weight at birth were greater for boys than for the general population. The observed pattern of head and body shape indicated that dwarfism occurred with age as a result of the relatively short trunk and lower limbs. Skeletal abnormalities included a bell-shaped chest with the ratio of chest depth to chest width being significantly above the norm. The head and neck were relatively elongated, in comparison to body height, and tucked between narrow shoulders. The head had dolichocephalic shape, while the nose was short with wide nostrils. CONCLUSIONS: Multiple anthropometric measurements, including age ranges, allowed for the creation of a model that showed the most characteristic features of the MPS IVA phenotype.

Novel data on growth phenotype and causative genotypes in 29 patients with Morquio (Morquio-Brailsford) syndrome from Central-Eastern Europe.

Mucopolysaccharidosis type IVA, also known as Morquio (Morquio-Brailsford) syndrome results from accumulation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S), whereas the primary cause is mutations in the gene encoding galactosamine (N-acetyl)-6-sulfatase (GALNS). Phenotypically it seems to be a well-defined condition, with two main clinical forms: mild (attenuated) and severe, which are determined based on a combination of symptoms, i.e., enzymatic activity of GALNS, age of onset, and symptom severity. Nevertheless, the natural history of MPSIVA in relation to specific anthropometric parameters (growth, head circumference, body proportions, and face phenotype) is not precisely characterized. The aim of our work was to analyze the aforementioned anthropometric parameters, including correlation to molecular data (causative GALNS mutations).

Enzyme replacement therapy in an attenuated case of mucopolysaccharidosis type I (Scheie syndrome): a 6.5-year detailed follow-up.

We present the 6.5-year follow-up of a boy with Scheie syndrome whose therapy was initiated at age 2.5 years. Detailed anthropometric features, echocardiography, ophthalmologic and audiologic examinations, psychologic tests, joint range of motion, skeletal radiographs, ultrasound studies of liver and spleen volumes, urinary glycosaminoglycans, and antibodies were documented. After 6.5 years of enzyme replacement therapy, the patient experienced a decline in overall status, and the disease progressed significantly despite treatment. The patient's height at age 9 was equal to that at age 6. The patient developed heart insufficiency and a deterioration of airway flow. The patient's intelligence quotient remained unchanged, i.e., at the average level of 86 on the Terman-Merill Scale. Magnetic resonance imaging revealed cervical spinal canal stenosis and marked spinal cord compression with myelopathy. A worsening of carpal tunnel syndrome was also evident. Ophthalmologic evaluation revealed increased central corneal thickness and intraocular pressure. In audiologic assessment, the patient's results were similar to those after 3 years of treatment. The only benefit involved temporarily improved passive and active shoulder flexion. Overall, the benefit of enzyme replacement therapy with laronidase on Scheie syndrome appeared minimal.