Dataset Information

"Growth patterns in children with mucopolysaccharidosis type I-Hurler after hematopoietic stem cell transplantation: Comparison with untreated patients".

ABSTRACT: The impact of hematopoietic stem cell transplantation (HSCT) on growth in patients diagnosed with mucopolysaccharidosis I Hurler (MPS-IH) has been historically regarded as unsatisfactory. Nevertheless, the growth patterns recorded in transplanted patients have always been compared to those of healthy children. The objective of this study was to verify the impact of HSCT on MPS-IH long term growth achievements. The auxological data of 15 patients were assessed longitudinally and compared both to the WHO growth centiles for healthy individuals and to recently published curves of untreated MPS-IH children. Despite a progressive decrease after HSCT when estimated with reference to the WHO growth charts, median height SDS showed a progressive and statistically significant increase when comparing the stature recorded at each timepoint in our population to the curves of untreated MPS-IH individuals (from -0.39 SDS at t₀ to +1.35 SDS 5 years after HSCT, p value < 0.001 and to +3.67 SDS at the age of 9 years, p value < 0.0001). In conclusion, though not efficient enough to restore a normal growth pattern in MPS-IH patients, we hereby demonstrate that HSCT positively affects growth and provides transplanted patients with a remarkable height gain compared to untreated gender- and age- matched individuals.

SUBMITTER: Cattoni A

PROVIDER: S-EPMC8361197 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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"Growth patterns in children with mucopolysaccharidosis type I-Hurler after hematopoietic stem cell transplantation: Comparison with untreated patients".

Cattoni Alessandro A Chiaraluce Sofia S Gasperini Serena S Molinari Silvia S Biondi Andrea A Rovelli Attilio A Parini Rossella R

Molecular genetics and metabolism reports 20210809

The impact of hematopoietic stem cell transplantation (HSCT) on growth in patients diagnosed with mucopolysaccharidosis I Hurler (MPS-IH) has been historically regarded as unsatisfactory. Nevertheless, the growth patterns recorded in transplanted patients have always been compared to those of healthy children. The objective of this study was to verify the impact of HSCT on MPS-IH long term growth achievements. The auxological data of 15 patients were assessed longitudinally and compared both to ...[more]

PMID: 34408967

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Project description: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 untreated infants < 1 year of age with severe mucopolysaccharidosis type I who had undergone evaluation for hematopoietic cell transplantation. We recorded left ventricular chamber dimensions, septal and posterior wall thicknesses, ventricular function, and aortic sinus diameters. We evaluated mitral and aortic valves for increased thickness, regurgitation, and stenosis. RESULTS:Average age (7M, 6F) was 221 (range 25-347) days. Left ventricular chamber dimension was ?2 SD of normal in 3/13; wall thicknesses were ?2 SD of normal in 2/13 infants. Systolic function was normal. Mitral valves were thickened in all infants; mitral regurgitation was present in 9/13, but significant in only three infants. Aortic valves were thickened in 10/13, but no infant had significant aortic regurgitation. Neither mitral nor aortic stenosis occurred. Aortic roots were dilated to ?2 SD of normal in 5/13. CONCLUSIONS:Characteristic cardiac features of severe mucopolysaccharidosis type I can be seen in infancy. Mitral and aortic valve thickening are nearly universally present, even in the youngest infants. In 20-30 % of infants, other abnormalities such as left ventricular dilation, increased wall thickness, and mild mitral/aortic regurgitation may occur. Aortic root dilation is a frequent finding. Early intervention with enzyme replacement therapy may minimize the incidence and severity of cardiac findings in these infants. SUMMARY: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. In our study of 13 infants with severe untreated MPS I < 1 year of age, mitral and aortic valve thickening was nearly universally present and aortic root dilation was frequent. Despite this, we found a lower incidence of left ventricular hypertrophy and both a lower incidence and milder expression of mitral and aortic valve dysfunction than previously reported in older children. These findings suggest that earlier intervention, including neonatal screening, may be of benefit to children with severe MPS I.

Project description:Mucopolysaccharidosis I-Hurler (MPS I-H) is the most severe form of a metabolic genetic disease caused by mutations of IDUA gene encoding the lysosomal α-L-iduronidase enzyme. MPS I-H is a rare, life-threatening disease, evolving in multisystem morbidity including progressive neurological disease, upper airway obstruction, skeletal deformity and cardiomyopathy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the gold standard for the treatment of MPS I-H in patients diagnosed and treated before 2-2.5 years of age, having a high rate of success. Beyond the child's age, other factors influence the probability of treatment success, including the selection of patients, of graft source and the donor type employed. Enzyme replacement therapy (ERT) with human recombinant laronidase has also been demonstrated to be effective in ameliorating the clinical conditions of pre-transplant MPS I-H patients and in improving HSCT outcome, by peri-transplant co-administration. Nevertheless the long-term clinical outcome even after successful HSCT varies considerably, with a persisting residual disease burden. Other strategies must then be considered to improve the outcome of these patients: one is to pursue early pre-symptomatic diagnosis through newborn screening and another one is the identification of novel treatments. In this perspective, even though newborn screening can be envisaged as a future attractive perspective, presently the best path to be pursued embraces an improved awareness of signs and symptoms of the disorder by primary care providers and pediatricians, in order for the patients' timely referral to a qualified reference center. Furthermore, sensitive new biochemical markers must be identified to better define the clinical severity of the disease at birth, to support clinical judgement during the follow-up and to compare the effects of the different therapies. A prolonged neuropsychological follow-up of post-transplant cognitive development of children and residual disease burden is needed. In this perspective, the reference center must guarantee a multidisciplinary follow-up with an expert team. Diagnostic and interventional protocols of reference centers should be standardized whenever possible to allow comparison of clinical data and evaluation of results. This review will focus on all these critical issues related to the management of MPS I-H.

Dataset Information

"Growth patterns in children with mucopolysaccharidosis type I-Hurler after hematopoietic stem cell transplantation: Comparison with untreated patients".

Publications

"Growth patterns in children with mucopolysaccharidosis type I-Hurler after hematopoietic stem cell transplantation: Comparison with untreated patients".

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