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

Abstract

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.

Clinical and Technological Dependence Characteristics on a Series of Brazilian Cases with Infantile Onset Pompe Disease in Enzyme Replacement Therapy

“…Concerning hearing impairment, the literature reports a prevalence of more than 90% among children with classic IOPD, with persistent hearing loss during ERT treatment, not correlated with the age of the patient [22] [61], which compared to our study, reflects probably underdiagnoses of this comorbidity.…”

“…Since the ERT implementation, systematic follow-up of treated PD cases has become essential and has been the focus of recent studies. Significant advances in the understanding of IOPD have been occurring continuously through care interdisciplinary collaboration for this condition [61] [64].…”

Newborn Screening for Pompe Disease

“…For example, some patients with IOPD receiving ERT present with learning disorders as neurological manifestations. Currently available rhGAA therapy cannot cross the blood-brain barrier [61,62]. Moreover, patients with LOPD detected in NBS can receive follow-up and early intervention before exhibiting deterioration of PD symptoms [32].…”

Classic infantile Pompe patients approaching adulthood: a cohort study on consequences for the brain

“…These findings contrast with those of our previous study and of four other studies on intelligence in classic infantile Pompe disease, where cognitive development was stable, ranging from normal to mildly delayed. 13,15,16,25 Only one case report on a 4-year-old patient and a recent case report on a 9-year-old expressed concerns about 'a not yet fully described CNS phenotype'. 23 Prompted by the potential effect of the disease on intellectual performance shown by MRI, we performed additional neuropsychological tests, whose results showed a consistent neuropsychological profile.…”