Clinical analysis of late-onset methylmalonic acidaemia and homocystinuria, cblC type with a neuropsychiatric presentation

Cobalamin-C (cblC) type secondary to MMACHC gene mutations is characterised by both methylmalonic acidaemia and homocystinuria, which is the most common inborn errors of intracellular cobalamin metabolism. Depending on the initial manifestation, there are two types of cblC, early-onset and late-onset. The early-onset type of cblC, the most common type, typically develops in infants and children during the first year after birth. In contrast, late-onset cblC is less common and occurs in adolescents and adults.1 Since late-onset cblC commonly presents with atypical clinical symptoms with no obvious family history, it is often misdiagnosed. We report five cases of late-onset cblC with a neuropsychiatric presentation. Our study provides important clinical data for understanding late-onset cblC. This study included five patients (9–35 years of age) who were diagnosed with late-onset clbC at the First Affiliated Hospital of Zhengzhou University. All patients underwent gas chromatography mass spectrometry (GC/MS) to measure urine concentrations of organic acids and tandem mass spectrometry (MS/MS) to measure plasma amino acid levels (MILS INTERNATIONAL, Japan). Serum levels of total homocysteine (tHCy) were determined using an enzymatic cycling assay (Roche MODULAR P800). The serum levels of folate and vitamin B12 were determined using an automatic biochemical analyser (Abbott ARCHITECT i2000SR). All patients underwent routine blood tests to assess liver and kidney function, blood coagulation and blood glucose levels. Mutations in the MMACHC gene were detected using PCR and DNA sequencing (Department of Medical Genetics, Peking University Health Science Center). All patients underwent cranial MRI, spinal MRI or an electrophysiological examination. MRI data were obtained with a 3.0 T MRI system (Siemens, Germany). Each patient was given T1-weighted, T2-weighted, fast fluid-attenuated inversion recover, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) sequences. All patients received methylcobalamin (methycobal, intravenous, 0.5–1 mg/day), folic acid (oral, 5 mg/day) and betaine (oral, 3–6 g/day), and were followed for …