Andreas Schulze: “Improved outcomes in early treated GAMT deficiency – a sibling study”
SHORT SUMMARY
This poster highlights the benefits of early diagnosis of GAMT by comparing outcomes for GAMT sibling pairs- one of which was diagnosed at a younger age, and the other at an older age.
ABSTRACT
Background: Singular observations in GAMT deficiency, an ultra-rare, severe neurodevelopmental disorder, imply the benefit of early, presymptomatic treatment.
Methods: Four GAMT- and 8 age-matched control sibling pairs were enrolled. Based on structured interviews with 4 GAMT families a Redcap questionnaire was constructed. For example, parents were asked to indicate whether and when their child achieved specific milestones, achieved them with support, or did not achieve them. Questions included developmental milestones, fine motor-, cognitive-, self-care-, and social skills, behavior, coordination, and therapy/support.
Results: GAMT sibling pairs were diagnosed at 0.0/5.6, 0.0/0.8, 1.1/5.8, and 3.8/8.8 y (younger/older), with current age of 11. 4/16.8 y (9.0-13.6/14.0-18.7) (mean (range), younger/older). The healthy controls were 9.9/13.5 y (4.9-12.0/8.8-16.0). In interviews, the parents identified intellectual level, communication, and self-care skills as the major difference between their two children with GAMT. Using the questionnaire responses, we compared the older child with its younger sibling in each pair. In GAMT, the comparison revealed consistent and distinct differences in every tested domain with the younger sibling performing better than its older sibling. There was no such difference in control sibling pairs. We further assessed GAMT outcome of early treatment (initiated <13 months, n=4) vs late treatment (initiated >3 years, n=4). There was normal to almost normal outcome in the early treatment group, while all children with late treatment demonstrated mostly large deficits in all investigated domains. Conclusion: This study convincingly confirms the notion that early initiation of treatment results in much improved outcomes in children with GAMT deficiency. Early identification of affected individuals required for timely treatment, ideally in the presymptomatic phase of the disease, makes universal newborn screening for GAMT mandatory.