Abstract
Hyperhomocysteinemia is a common medical condition observed in patients with aminoaciduria. Deficiency in cystathionine beta-synthase, metabolism of cobalamin associated C, peroxiredoxin 1, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, LMBR1 domain containing 1, 5-methyltetrahydrofolate-homocysteine methyltransferase or 5,10-methylenetetrahydrofolate reductase (MTHFR) all can result in an elevation in plasma homocysteine, which has been reported to be a risk factor of vascular events, such as atherosis, acute myocardial infarction and cerebral stroke. Hyperhomocysteinemia due to the deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR; also known as 5,10-methyl THR reductase) is an autosomal recessive rare disease caused by defects in the MTHFR gene. The clinical manifestations of this disorder are heterogeneous, ranging from asymptomatic to severe neurological disorders. However, hydrocephalus has seldomly been reported in patients with MTHFR deficiency. The present study thus describes a case of severe MTHFR deficiency in an infant, whose main manifestation was hydrocephalus. The clinical course and genotype of the patient were also examined. Specifically, a 4-month-old boy with hydrocephalus was admitted to hospital. Clinical examinations and genetic sequencing of the patient were performed to determine the probable causative factors. A physical examination revealed that the patient had developmental delay and progressive hydrocephalus. Amino acid analysis of the blood revealed an enhancement in serum homocysteine levels and a decrease in blood methionine and free carnitine levels. The organic acid levels in urine were normal. Therefore, he was diagnosed with hyperhomocysteinemia. Targeted next-generation sequencing was performed to determine the pathogenetic gene in this case. A paternal mutation c.1530G>A (p.K510K) and a maternal mutation c.233C>A (p.S78X) were identified. Previous experimental evidence indicated that these two mutations were all pathogenic; therefore, this patient was ultimately diagnosed with MTHFR deficiency. The patient in described herein study presented with severe progressive hydrocephalus in association with a delayed developmental milestone. According to the clinical and genetic tests, the patient was diagnosed with severe MTHFR deficiency. It thus is recommended that screening for metabolites and performing gene sequencing in infants presenting with undisclosed hydrocephalus.
