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Infantile type of homocystinuria with N5,10-methylenetetrahydrofolate reductase defect
Insights
Two infants with N5,10-methylenetetrahydrofolate reductase deficiency experienced severe infantile symptoms and early death. A new diagnostic assay for this homocystinuria type may aid in early detection and heterozygote screening.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Medicine
Background:
- Homocystinuria is a group of inherited metabolic disorders.
- Defects in folate metabolism enzymes, like N5,10-methylenetetrahydrofolate reductase (MTHFR), can lead to homocystinuria.
- Previous reports detailed MTHFR deficiency with varying clinical presentations.
Observation:
- Two infants presented with a severe, early-onset form of homocystinuria.
- Clinical features included apnea, seizures, coma, and rapid decline, leading to death within the first year of life.
- These severe symptoms distinguished them from previously reported cases with similar biochemical defects.
Findings:
- The infants had defective N5,10-methylenetetrahydrofolate reductase activity in multiple organs.
- This distinct clinical course suggests a novel "infantile type" of MTHFR deficiency.
- A diagnostic assay using peripheral leukocytes for MTHFR activity was developed.
Implications:
- The identification of an "infantile type" of MTHFR deficiency expands the clinical spectrum of this disorder.
- The leukocyte assay offers a potential tool for diagnosing affected infants.
- This assay could also facilitate the identification of carriers (heterozygotes) for MTHFR deficiency, enabling genetic counseling.
Abstract:
Two infants of homocystinuria with a defective activity of the N5,10-methylenetetrahydrofolate reductase in the liver, kidney, brain and/or leukocytes were reported. Contrary to four cases with similar biochemical defects reported up to date, the two cases of ours demonstrated peculiar clinical features characterized by an early onset in infancy, fits of apnea and seizures, downhill course with coma, and death within one year of life. Thus "an infantile type" of this disorder was advanced as a new clinical entity. Assay for the N5,10-methylenetetrahydrofolate reductase activity using peripheral leukocytes was established and might be useful for a diagnosis of this disorder and also for detection of heterozygotes.