A study of Iraqi patients with homocysteine remethylation disorders in a tertiary pediatric centre

Hyperhomocysteinemia is a group of inherited homocysteine metabolism disorders characterised by elevated blood homocysteine levels (total homocysteine >15 μM). Homocystinuria is classified into two main homocysteine metabolism disorders. Classical Homocystinuria is caused by a deficiency of the pyridoxine-dependent enzyme cystathionine beta-synthase in the trans‑sulfuration pathway. Non-classical Homocystinuria is a group of disorders affecting the interconversion of methionine to homocysteine through the re-methylation pathway.

This study aims to describe the clinical, biochemical, and genetic profiles of patients with re-methylation disorders.

A cohort study was conducted at the metabolic clinic of Children Welfare Teaching Hospital in Baghdad from the 1st of December 2021 to the 1st of December 2022. The study included fifteen patients who met the following criteria: (1) elevated serum homocysteine levels (>15 μmol/L); (2) low or normal blood methionine levels (12-40 μmol/L). Results: fourteen MTHFR patients underwent statistical analysis, and one CblC patient was assessed separately. MTHFR patients comprised nine females and five males. The mean age at presentation was 7.1 years ±4.5, ranging from 1 to 16 years. Consanguineous marriages were reported in 13 patients. A family history of a similar disorder was documented in 73 % of cases. Among the families, four had two affected siblings. The two main reported clinical manifestations were gait disturbance (10/14, 71.4 %) and cognitive impairment/intellectual disability (6/14, 42.8 %). Brain MRI was conducted for all studied patients, with leukodystrophy being the most common finding (8/14, 57.1 %). Molecular testing revealed variants in MTHFR in 14 patients, and MMACHC in one patient.

According to this study, individuals with homocysteine re-methylation disorders can manifest symptomatology such as neuroregression, psychomotor delay, and whiter matter changes earlier than anticipated. And these disorders are amenable to treatment. Genetic testing is crucial in identifying the specific mutation type and guiding definitive treatment.