200 Section - Clinical Case Report: Global Developmental Delay in a Child With an MTHFR Gene Mutation – Multidisciplinary Approach and Therapeutic Potential of Integrated Rehabilitation

The patient was diagnosed with global developmental delay (GDD) associated with a homozygous MTHFR gene mutation. Biochemical evaluation revealed elevated homocysteine levels and reduced folate metabolism activity, supporting the mutation’s pathogenic relevance. The clinical presentation – delayed motor, cognitive, and language milestones – was consistent with GDD secondary to an inborn error of folate metabolism.

Case Description:

This report discusses the case of a 3-year-old male patient, born to consanguineous parents, presenting with severe GDD and gastrostomy dependence. Neurological examination demonstrated axial hypotonia and poor postural control. Laboratory tests showed hyperhomocysteinemia, and genetic testing identified a pathogenic MTHFR mutation. In the initial WeeFIM assessment, the patient scored 26 points, indicating complete dependence. Metabolic treatment and a multidisciplinary rehabilitation program were initiated, including motor physiotherapy, occupational therapy, speech therapy, and neuropsychological stimulation. Following the intervention period, significant functional gains were observed, particularly the acquisition of trunk control and improved social interaction. Although, the patient remains nearly fully dependent on gastrostomy.

Discussions:

MTHFR mutations impair folate metabolism, potentially leading to developmental delay. While most publications emphasize metabolic management, fewer studies detail rehabilitation outcomes. Guided by the International Classification of Functioning, Disability and Health’s principles, the therapeutic plan targeted postural control, muscular strength, and improvement of communication and autonomy. This highlights the importance of early, structured, multidisciplinary intervention in optimizing developmental gains and the value of standardized tools such as WeeFIM to monitor functional progress. 

Conclusions:

These findings highlight the relevance of a structured, multidisciplinary rehabilitation program in children with GDD secondary to MTHFR mutations. Consistent functional gains observed through quantitative assessment underscore the therapeutic potential of integrated rehabilitation in a condition traditionally approached from a primarily metabolic perspective. This reinforces the importance of coordinated interventions and suggests that rehabilitation plays a central role in improving functional outcomes.