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Clinical analysis of late-onset methylmalonic acidaemia and homocystinuria, cblC type with a neuropsychiatric presentation
  1. Yan-ru Liu1,
  2. Yang-fei Ji1,
  3. Ya-li Wang2,
  4. Bo-ai Zhang1,
  5. Gui-yuan Fang1,
  6. Jing-tao Wang1,
  7. Gui-fang Sun1,
  8. Hong Lu1
  1. 1 Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  2. 2 Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  1. Correspondence to Professor Hong Lu ( and Bo-ai Zhang, Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, Zhengzhou 450052, China (zhangboaidoctor{at}

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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.

Materials and methods

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 …

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  • Contributors Y-rL and Y-fJ contributed equally to this study. Yan-ru Liu and Yang-fei Ji were involved in writing the manuscript. Ya-li Wang was the patients' consultant psychiatrist, and the other authors were the patients' consultant neurologists. All authors were involved in the management of the patients. Bo-ai Zhang and Hong Lu were involved in the interpretation and critical revision of the manuscript.

  • Funding This study was supported by a grant from the Foundation of He’nan Educational Committee (No. 14A360010).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University) and with the Helsinki Declaration of 1975, as revised in 2000 (5).

  • Provenance and peer review Not commissioned; externally peer reviewed.