Faculty advisor: Julie EisengartThis research was supported by the Undergraduate Research Opportunities Program (UROP)

Eisengart, J.B

Kaizer, A.

Lund, T.

Miller, W.

Orchard, P.J

Spurlock, Katherine

University of Minnesota Digital Conservancy

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
   
                      
 
 
																																																																	MPS	IH	
N 8 
Male 3 (37.5%) 
Age (months) at 
Transplant 
8.74 (1.96) 
     Median (range) 8.76 (5.03-11.93) 
ERT delivery 
     IV 8  
     IV + IT 4  
Early IQ Score: 
     Baseline 91.6 (7.35) 
     Year 1 87.9 (8.55) 
     Missing Year 1 1 (12.5%) 
     Year 2 93.4 (15.0) 
70
80
90
10
0
11
0
12
0
Time
M
IQ
0 1 2
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Mean Fit Slope=1.445 [95% CI: (−4.43,7.32)], p=0.63
● Patient
Mean Fit
Patient Characteristics 
Time (Years from Transplant) 
Ea
rly
 IQ
 S
co
re
 (M
 =
 1
00
 ±
 1
5)
 
Values are mean (SD) or N (%) unless otherwise indicated. 
   METHODS  
•  Assessed cognitive outcomes of 8 patients with Hurler 
syndrome: 
•  Transplanted at less than 12 months of age 
•  Transplanted since 2005 to reflect modern HCT 
practice 
•  All patients received ERT in peri tranplant period 
•  Longitudinal cognitive follow up data available at least 2 years 
following HCT for all patients. 
•  Examined cognitive scores before transplant and at 1 and 2 
years following HCT. 
•  Early IQ scores (IQ) were measured with the Mullen Scales of 
Early Learning and Bayley Scales of Infant and Toddler 
Development, Third Edition. 
•  Early IQ scores were analyzed longitudinally. Generalized 
estimating equations were used with robust variance estimation 
to determine the mean fit and p-value with an autoregressive 
(AR1) correlation structure to account for correlated 
observations. 
Cognitive outcomes in Hurler syndrome following transplant before age 12 months  
Spurlock,	K.1,	Orchard,	P.J.2,	Miller,	W.2,	Lund,	T.2,	Kaizer,	A.3,	Eisengart,	J.B.2,		
	1College	of	Biological	Sciences,	University	of	Minnesota,	2Department	of	Pediatrics,	University	of	Minnesota	Medical	School,	3Department	of	Biosta?s?cs	and	Informa?cs,	University	of	Colorado,	Colorado	School	of	Public	Health		
  OBJECTIVE    To characterize cognitive outcomes of patients with  
Hurler syndrome transplanted prior to 12 months of 
life. 
   BACKGROUND  
•  Mucopolysaccharidosis (MPS) type I is a rare autosomal 
recessive LSD caused by deficiency in the enzyme α-L-
iduronidase. 
•  Severe form of MPSI, Hurler syndrome, is characterized by 
progressive neurological involvement and multisystem disease 
resulting in death by end of early childhood if untreated. 
•  Individuals with Hurler syndrome follow a predictable 
trajectory of normal cognitive development in first year of life, 
slowing in second year, and rapid decline thereafter.  
•  Allogeneic hematopoietic stem cell transplantation (HCT) is 
the standard of care as it stabilizes deterioration and extends 
survival. 
•  Enzyme replacement therapy (ERT) as an adjunct to HCT 
reduces morbidity and mortality and may lead to more 
favorable cognitive outcomes. 
•  Overwhelming evidence that earlier treatment with HCT leads 
to improved cognitive outcomes. 
 DISCUSSION  
•  No evidence of loss in IQ points from time period prior to HCT to 2 
years afterward. 
•  Likely cognitive benefit when transplant is conducted at younger 
than 12 months of life. 
•  Finding is different from the general literature which has a broader 
range of transplanted children and shows there is generally a loss of 
IQ points following HCT. 
•  Findings further support research that indicates earlier treatment 
leads to favorable outcomes. 
•  Important at the dawn of newborn screening. 
 FUTURE DRECTIONS  
•  Longer-term analyses of a larger cohort 
transplanted at less than 12 months to 
determine if cognitive outcomes remain 
superior from those transplanted at older 
ages. 
•  Compare this group to children 
transplanted at 12 months and older 
while controlling for additional factors 
such as baseline IQ, transplant 
preparation, and ERT. 
RESULTS 
IQ OVER TIME 
•  Five patients (62.5%) had a 2-year post-HCT 
IQ score equal to or higher than their 
baseline IQ score 
•  Average change = 12.4 points 
•  Three patients (37.5%) had a 2-year post-
HCT IQ score declined from baseline 
•  Average loss = 12.7 points 
•  IQ scores at 2 years following HCT were not different 
from baseline P = 0.63. 
	
J IVE 
IRECTIONS 


Cognitive outcomes in Hurler syndrome following transplant before age 12 months

https://conservancy.umn.edu/bitstream/handle/11299/196412/Spurlock%20Research%20Poster%202018.pdf?sequence=1&isAllowed=y

Cognitive outcomes in Hurler syndrome following transplant before age 12 months

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