Work

An encephalitis-like syndrome in an adult with methylmalonic acidemia and hyperhomocysteinemia: A case report

Year: 2026

Type: article

Abstract: RATIONALE: Methylmalonic acidemia with hyperhomocysteinemia may remain unrecognized until adulthood. When fever, altered consciousness, psychiatric symptoms, cerebrospinal fluid (CSF) abnormalities, and electroencephalographic slowing dominate the presentation, infectious or autoimmune encephalitis is often considered first. Glutamic acid decarboxylase 65 antibody positivity may further complicate the diagnostic interpretation. PATIENT CONCERNS: A 56-year-old man presented with fever and slowed responses for 15 days, followed by disorganized speech, visual hallucinations, episodes of impaired consciousness, and pyramidal signs. DIAGNOSES: Total homocysteine was > 100 µmol/L, propionylcarnitine (C3) was 22.42 µmol/L, and the C3/acetylcarnitine ratio was 0.83. Urinary organic acid analysis indicated increased methylmalonic acid and methylcitrate. Serum and CSF glutamic acid decarboxylase 65 antibodies were positive (titers, 1:100 and 1:3.2, respectively); however, the remaining autoimmune encephalitis antibody panel was negative, magnetic resonance imaging was nonspecific, and whole-exome sequencing revealed no clearly pathogenic variant. The findings supported methylmalonic acidemia with hyperhomocysteinemia on biochemical grounds and were clinically suggestive of a cobalamin metabolism-related disorder. INTERVENTIONS: He received vitamin B12, vitamins B1 and B6, folic acid, levocarnitine, intravenous immunoglobulin, empirical anti-infective treatment, mechanical ventilation, and intensive supportive care. OUTCOMES: Following concurrent metabolic, immunologic, anti-infective, and intensive supportive treatments, his clinical symptoms improved. Total homocysteine decreased to 16.04 µmol/L, C3 to 19.50 µmol/L, and the C3/acetylcarnitine ratio to 0.40; CSF protein decreased from 1.78 to 0.80 g/L. Because these interventions were delivered simultaneously, the clinical and biochemical changes could not be attributed to any single treatment. At 6-month telephone follow-up, the family reported no recurrent fever, hallucinations, disorganized behavior, or marked disturbance of consciousness. LESSONS: In adults with an encephalitis-like syndrome, recurrent neurologic symptoms, anemia, pyramidal signs, and marked hyperhomocysteinemia should prompt early metabolic screening. An antibody result should be interpreted alongside the clinical phenotype, biochemical profile, imaging findings, and CSF data, rather than used alone to assign etiology.

Source: Medicine

DOI: 10.1097/md.0000000000051467

Authors: Rongjin Zhang, Xiaona Sheng

Institution: Second Hospital of Hebei Medical University

Language: English

Topic: Metabolism and Genetic Disorders

Subfield: Clinical Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,950