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Expanding the Phenotypic Spectrum of Methylenetetrahydrofolate Reductase (MTHFR) Deficiency in Childhood: A Case
Eimear Loftus1, Zaineb Elbishari1, Patricia Fitzsimons2
1National Centre for Inherited Metabolic Disorders Children's Health Ireland (CHI) Dublin Republic of Ireland.
Abstract:
Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare inborn error of folate metabolism. A number of phenotypic findings have been identified to date, and we hereby wish to expand its phenotype based on our Irish experience of the condition. We follow three children with MTHFR deficiency in our National Centre for Inherited Metabolic Disorders, giving an estimated point prevalence of approx. 0.08 cases per 100,000 in the Republic of Ireland. Our first case was referred for a metabolic opinion at 19 months of age. She had a history of global developmental delay with hypotonia, microcephaly, nystagmus, rash, and seizures. The second patient presented at 12 years of age with an osteopenic femoral fracture on the background of low body mass index (BMI). The third case presented at ten and a half years of age with acute mood disturbance with challenging behavior and a history of focal seizures and intellectual disability. It has been reported that early treatment may provide clinical benefit; however, we wish to acknowledge the varying responses to treatment despite pleasing metabolic control in our patients. MTHFR deficiency is a challenging diagnosis in childhood, given its low prevalence, complex phenotypes, and varying responses to treatment. Presymptomatic treatment further to early diagnosis through newborn screening may further improve outcomes.
Insights
Methylenetetrahydrofolate reductase (MTHFR) deficiency, a rare folate metabolism disorder, presents diverse symptoms in children. Early diagnosis and treatment are crucial for improving outcomes in MTHFR deficiency.
Area of Science:
- Genetics and Metabolism
- Inborn errors of metabolism
- Folate metabolism
Background:
- Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare inherited metabolic disorder.
- Phenotypic variability is a known characteristic of MTHFR deficiency.
- Understanding the full spectrum of MTHFR deficiency is essential for accurate diagnosis and management.
Purpose of the Study:
- To expand the known phenotype of Methylenetetrahydrofolate reductase (MTHFR) deficiency.
- To report on the clinical presentation and outcomes of three pediatric cases in Ireland.
- To highlight the diagnostic challenges and treatment variability in MTHFR deficiency.
Main Methods:
- Case series following three children diagnosed with MTHFR deficiency.
- Clinical data collection including developmental milestones, physical findings, and neurological status.
- Estimation of point prevalence in the Republic of Ireland.
Main Results:
- The study identified diverse phenotypes including global developmental delay, hypotonia, microcephaly, seizures, osteopenia, and mood disturbances.
- Estimated point prevalence of MTHFR deficiency in Ireland is approximately 0.08 per 100,000.
- Patients showed varying responses to treatment despite achieving metabolic control.
Conclusions:
- MTHFR deficiency presents with a complex and expanding phenotype in childhood.
- Early diagnosis through newborn screening and prompt treatment may improve clinical outcomes.
- The variability in treatment response underscores the need for personalized management strategies for MTHFR deficiency.
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