Cognitive outcome of patients with classic infantile Pompe disease receiving enzyme therapy

Ebbink, Berendine J.; Aarsen, Femke K.; Gelder, Carin M. Van; Hout, J. M. P. van den; Weisglas‐Kuperus, Nynke; Jaeken, Jaak; Lequin, Maarten H.; Arts, W.F.M.; Ploeg, Ans T. van der

doi:10.1212/wnl.0b013e3182553c11

Cited by 67 publications

(62 citation statements)

References 32 publications

(22 reference statements)

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“…This observation underscored the importance of looking beyond an overall measure of cognitive ability to determine participants’ relative strengths and weaknesses. This was subsequently reported by Ebbink et al [15,21]. In examining the latest administrations of a Wechsler scale for 8 participants in this study (Table 6), the Processing Speed Index was the lowest score for only two individuals.…”

Section: Discussionsupporting

confidence: 78%

“…In another study of long term survivors, Ebbink and colleagues [15] examined the cognitive abilities of 10 children with classic IOPD treated with ERT over time. Those children born before 2004 ( n = 5) were assessed serially using the BSID-II through 3.1 years of age and the Snijders Oomen Nonverbal Intelligence Test-Revised (SON-R) [16] at 5 years of age.…”

Section: Introductionmentioning

confidence: 99%

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Cognitive and academic outcomes in long-term survivors of infantile-onset Pompe disease: A longitudinal follow-up

Spiridigliozzi

Keeling

Ștefănescu

et al. 2017

Molecular Genetics and Metabolism

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This study examines the long-term cognitive and academic outcomes of 11 individuals with infantile onset Pompe disease (IOPD) (median age = 11 years, 1 month, range = 5 years, 6 months through 17 years of age) treated with enzyme replacement therapy from an early age. All participants (7 males, 4 females) were administered individual intelligence tests (Wechsler or Leiter scales or both), a measure of their academic skill levels (Woodcock-Johnson Tests of Achievement), and a screening measure of visual-motor integration ability (Beery-Buktenica). Consistent with our earlier findings, median IQ scores for the entire group on the Wechsler (median = 84) and Leiter (median = 92) scales continue to fall at the lower end of the average range compared to same-aged peers. The median scores for the group on a measure of visual-motor integration (median = 76), visual perception (median = 74) and motor coordination (median = 60) were below average. Two distinct sub-groups emerged based on participants’ average or below average performance on the majority of academic sub-tests. Those participants with below average academic skills (n = 6) demonstrated average nonverbal cognitive abilities on the Leiter, but had weaknesses in speech and language skills and greater medical involvement. Their profiles were more consistent with a learning disability diagnosis than an intellectual disability. Two of these participants showed a significant decline (15 and 23 points, respectively) on repeated Wechsler scales, but one continued to earn average scores on the Leiter scales where the verbal and motor demands are minimal. Participants with average academic skills (n = 5) demonstrated average cognitive abilities (verbal and nonverbal) on the Wechsler scales and less medical involvement. Their speech and language skills appeared to be more intact. However, both groups earned below average median scores on the Beery-Buktenica motor coordination task. This study highlights the importance of using appropriate tests to capture both verbal and nonverbal abilities, considering each individual’s motor skills, speech and language abilities, hearing status and native language. This will allow for a more accurate assessment of whether there is a learning disability or an intellectual disability. Long-term outcomes may be related to the stability of an individual’s expressive and/or receptive language abilities over time. Changes in the speech and language domain may account for the decline in IQ observed in some IOPD long-term survivors, reflecting a learning disability rather than a decline in overall cognition or an intellectual disability. These observations, in conjunction with neuroimaging, will further our understanding of the neurocognitive profile of long-term IOPD survivors.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Cognitive and academic outcomes in long-term survivors of infantile-onset Pompe disease: A longitudinal follow-up

Spiridigliozzi

Keeling

Ștefănescu

et al. 2017

Molecular Genetics and Metabolism

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“…White matter involvement on brain MRI, and cognitive and behavioral impairment in these patients, has been reported in literature [28,29], but no seizures have been reported. Long term studies and more careful assessments are needed to better understand how imaging changes relate to cognition.…”

Section: Discussionmentioning

confidence: 99%

High dose IVIG successfully reduces high rhGAA IgG antibody titers in a CRIM-negative infantile Pompe disease patient

Rairikar

Kazi

Desai

et al. 2017

Molecular Genetics and Metabolism

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Alglucosidase alfa (rhGAA) has altered the course of an otherwise fatal outcome in classic infantile Pompe disease (IPD), which presents with cardiomyopathy and severe musculoskeletal involvement. However, the response to therapy is determined by several factors including the development of high and sustained antibody titers (HSAT) to rhGAA. Cross-reactive immunologic material (CRIM) negative patients are at the highest risk for development of HSAT. Immune tolerance induction (ITI) with methotrexate, rituximab, and intravenous immunoglobulin (IVIG) has been largely successful in preventing the immune response and in achieving tolerance when done in conjunction with enzyme replacement therapy (ERT) initiation. Reducing antibody titers in cases with an entrenched immune response remains a challenge in the field despite the use of multiple immunomodulatory agents. Success has been shown with addition of bortezomib to the ITI regimen, yet the prolonged course and potential risks with the use of such agents’ demands caution. We present here a 7-year-old CRIM-negative IPD patient who was not successfully tolerized by an ITI regimen with rituximab, methotrexate, and IVIG due to intolerability to the regimen and recurrent infections. She went on to develop HSAT, with significant clinical decline, loss of all motor abilities, and a fragile medical state, which made it challenging to institute the bortezomib based regimen to reduce HSAT. She had severe developmental delay, respiratory failure with invasive ventilation and tracheostomy, persistent hypotonia, ptosis of eyelids, diffuse severe osteopenia, contractures, and was completely G-tube fed. As a rescue mechanism, we treated her with high dose and high frequency IVIG in an attempt to reduce rhGAA IgG antibody titers (antibody titers; titers). Her titers saw a steady decline on weekly IVIG doses at 1 g/kg for 20 weeks. Subsequently when the IVIG regimen was altered to 1 g/kg every month, rising titers were detected and therefore the regimen was changed to a biweekly regimen. High dose IVIG resulted in an eightfold decrease in antibody titers. Clinically, she showed improvement with partial recovery of previously lost motor abilities, especially hand movements and better head and neck control than before. The regimen was safely tolerated with no hospitalizations. The effectiveness of IVIG as a single agent, in this case with multiple comorbidities and fragile clinical status, was lifesaving and may represent an effective, perhaps lifesaving rescue approach to reduce antibody titers.

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“…They were evaluated prospectively both developmentally and by neuroimaging. 114 Cognitive development at school age improved and ranged between normal and mildly delayed. Periventricular white matter abnormalities were found in 4 children.…”

Section: The University Of Kansas Medical Center Case Seriesmentioning

confidence: 99%

Pompe Disease

Dasouki¹,

Jawdat²,

Almadhoun³

et al. 2014

Neurologic Clinics

118

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Cognitive outcome of patients with classic infantile Pompe disease receiving enzyme therapy

Cited by 67 publications

References 32 publications

Cognitive and academic outcomes in long-term survivors of infantile-onset Pompe disease: A longitudinal follow-up

Cognitive and academic outcomes in long-term survivors of infantile-onset Pompe disease: A longitudinal follow-up

High dose IVIG successfully reduces high rhGAA IgG antibody titers in a CRIM-negative infantile Pompe disease patient

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