Growth in patients with mucopolysaccharidosis type III (Sanfilippo disease)

Mucopolysaccharidosis III (MPS III), known as Sanfilippo disease, is a lysosomal storage disorder mainly characterized by progressive neurodegeneration with cognitive decline and relatively attenuated somatic signs and symptoms. Although short stature is invariably present in patients with the other mucopolysaccharidoses, it has not been sufficiently addressed in MPS III. The aim of this study was to investigate growth data of a large Dutch MPS III cohort in order to construct growth charts for MPS III patients. Height, weight, head circumference (HC), and body mass index (BMI) data from 118 MPS III patients were used to construct reference curves, using the lambda, mu, sigma (LMS) method. Genotype-group comparisons for height standard deviation scores (SDS) were performed by Kruskal-Wallis analysis for different age groups. Birth weight and length were within normal ranges for gestational age and showed a significantly stunted growth from age 6 years onward. Mean final heights were 169.7 cm (-2.0 SDS) and 165.4 cm (-0.84 SDS) for adult male and female, patients, respectively. Phenotypic severity, as assessed by genotyping, correlated with growth pattern and final height. In addition, mean BMI and HC SDS were significantly higher when compared with Dutch standards for both boys and girls. Growth in MPS III is stunted mainly in patients with the severe phenotype. We provide disease-specific growth references that can be used for clinical management of MPS III patients and may be of value for future treatment studies.