Abstract
BackgroundHurler syndrome (MPS IH), the severe, neurodegenerative form of type one mucopolysaccharidosis, is associated with rapid neurocognitive decline during toddlerhood and multi-system dysfunction. It is now standardly treated with hematopoietic cell transplantation (HCT), which halts accumulating disease pathology and prevents early death. While norm-based data on developmental functioning in untreated children have previously demonstrated neurocognitive decline, advances in methodology for understanding the cognitive functioning of children with neurodegenerative diseases have highlighted that the previous choice of scores to report results was not ideal. Specifically, the lowest possible norm-based score is 50, which obscures the complete range of cognitive functioning at more advanced stages of neurodeterioration. To a set of cognitive data collected on a sample of untreated children, we applied a modern method of score analysis, calculating a developmental quotient based on age equivalent scores, to reveal the full range of cognitive functioning beneath this cutoff of 50, uncovering new information about the rapidity of decline and the profound impairment in these children.ResultsAmong 39 observations for 32 patients with untreated Hurler syndrome, the full array of cognitive functioning below 50 includes many children in the severely to profoundly impaired range. The loss of skills per time unit was 14 points between age 1 and 2. There was a very large range of developmental quotients corresponding to the norm-based cutoff of 50.ConclusionsThis report enables clarification of functioning at levels that extend beneath the floor of 50 in previous work. At the dawn of newborn screening and amidst a proliferation of new therapies for MPS I, these data can provide crucial benchmark information for developing treatments, particularly for areas of the world where transplant may not be available.
Highlights
Hurler syndrome (MPS IH), the severe, neurodegenerative form of type one mucopolysaccharidosis, is associated with rapid neurocognitive decline during toddlerhood and multi-system dysfunction
These valuable data were never published for those children who were not transplanted, such that the literature is lacking detailed information about declining cognitive age equivalent scores and developmental quotients related to age
We report 1) age at testing; 2) year of testing; 3) age equivalent score for the mental scale; 4) developmental quotient (DQ; defined as mental age divided by chronological age times 100 [15]); 5) Mental Development Index (MDI) for comparison to developmental quotient; and 6) age at death
Summary
Hurler syndrome (MPS IH), the severe, neurodegenerative form of type one mucopolysaccharidosis, is associated with rapid neurocognitive decline during toddlerhood and multi-system dysfunction. Earlier intervention owing to Shapiro et al Orphanet Journal of Rare Diseases (2018) 13:76 developmental trajectory was necessarily truncated at that level: It did not reveal the full range of how profoundly impaired children may be, obscuring the complete natural history of this disorder [12] It was not until the results of early HCT were published in 1996 and 1998 [13, 14] that age equivalent scores were first used, and since this methodology has become the gold standard for demonstrating cognitive functioning in highly impaired patients [3, 7, 9, 15,16,17,18,19]. Assessment of completely untreated children is essentially impossible in the modern era; the current study is not repeatable but offers crucial information about cognitive age equivalents, described comprehensively
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