Dataset Information

Proposal of an Algorithm to Early Detect Attenuated Type I Mucopolysaccharidosis (MPS Ia) among Children with Growth Abnormalities.

ABSTRACT: Background and Objectives: Diagnostic delay is common in attenuated Mucopolysaccharidosis Type I (MPS Ia) due to the rarity of the disease and the variability of clinical presentation. Short stature and impaired growth velocity are frequent findings in MPS Ia, but they rarely raise suspicion as paediatric endocrinologists are generally poorly trained to detect earlier and milder clinical signs of this condition. Materials and Methods: Following a consensus-based methodology, a multidisciplinary panel including paediatric endocrinologists, paediatricians with expertise in metabolic disorders, radiologists, and rheumatologists shared their experience on a possible clinical approach to the diagnosis of MPS Ia in children with short stature or stunted growth. Results: The result was the formation of an algorithm that illustrates how to raise the suspicion of MPS Ia in a patient older than 5 years with short stature and suggestive clinical signs. Conclusion: The proposed algorithm may represent a useful tool to improve the awareness of paediatric endocrinologists and reduce the diagnostic delay for patients with MPS Ia.

SUBMITTER: Baronio F

PROVIDER: S-EPMC8780542 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proposal of an Algorithm to Early Detect Attenuated Type I Mucopolysaccharidosis (MPS Ia) among Children with Growth Abnormalities.

Baronio Federico F Zucchini Stefano S Zulian Francesco F Salerno Mariacarolina M Parini Rossella R Cattoni Alessandro A Deodato Federica F Gaeta Alberto A Bizzarri Carla C Gasperini Serena S Pession Andrea A

Medicina (Kaunas, Lithuania) 20220108 1

<i>Background and Objectives:</i> Diagnostic delay is common in attenuated Mucopolysaccharidosis Type I (MPS Ia) due to the rarity of the disease and the variability of clinical presentation. Short stature and impaired growth velocity are frequent findings in MPS Ia, but they rarely raise suspicion as paediatric endocrinologists are generally poorly trained to detect earlier and milder clinical signs of this condition. <i>Materials and Methods</i>: Following a consensus-based methodology, a mult ...[more]

PMID: 35056405

Similar Datasets

Project description:ImportanceMolecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking.ObjectiveTo assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies.Design, setting, and participantsThis cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children's hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018.Main outcomes and measuresGene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry.ResultsA total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was -15.2 (0.91) and normal was -19.5 (0.48); P < .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) -2.9 (0.42) and for normal was 2.2 (0.45); P < .001. Associations were found between disease severity or transepidermal water loss and TH2 (IL-33 and IL-4R) and TH17/TH22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools).Conclusions and relevanceIn this study, tape strips provide a minimally invasive alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.

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.

Dataset Information

Proposal of an Algorithm to Early Detect Attenuated Type I Mucopolysaccharidosis (MPS Ia) among Children with Growth Abnormalities.

Publications

Proposal of an Algorithm to Early Detect Attenuated Type I Mucopolysaccharidosis (MPS Ia) among Children with Growth Abnormalities.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets