Clinical and electroencephalogram characteristics of methylmalonic acidemia with MMACHC and MUT gene mutations
Yujun Yuan1, Ying Ma2, Qiong Wu2
1Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
Objective:
This study investigated the clinical, imaging, and electroencephalogram (EEG) characteristics of methylmalonic acidemia (MMA) with nervous system damage as the primary manifestation.
Methods:
From January 2017 to November 2022, patients with nervous system injury as the main clinical manifestation, diagnosed with methylmalonic acidemia by metabolic and genetic testing, were enrolled and analyzed. Their clinical, imaging, and electroencephalogram data were analyzed.
Results:
A total of 18 patients were enrolled, including 15 males and 3 females. The clinical symptoms were convulsions, poor feeding, growth retardation, disorder of consciousness, developmental delay, hypotonia, and blood system changes. There were 6 cases (33%) of hydrocephalus, 9 (50%) of extracerebral space widened, 5 (27%) of corpus callosum thinning, 3 (17%) of ventricular dilation, 3 (17%) of abnormal signals in the brain parenchyma (frontal lobe, basal ganglia region, and brain stem), and 3 (17%) of abnormal signals in the lateral paraventricular. In addition, there were 3 cases (17%) of cerebral white matter atrophy and 1 (5%) of cytotoxic edema in the basal ganglia and cerebral peduncle. EEG data displayed 2 cases (11%) of hypsarrhythmia, 3 (17%) of voltage reduction, 12(67%) of abnormal discharge, 13 (72%) of abnormal sleep physiological waves or abnormal sleep structure, 1 (5%) of immature (delayed) EEG development, and 8 (44%) of slow background. There were 2 cases (11%) of spasms, 1 (5%) of atonic seizures, and 1 (5%) of myoclonic seizures. There were 16 patients (89%) with hyperhomocysteinemia. During follow-up, 1 patient was lost to follow-up, and 1 died. In total, 87.5% (14/16) of the children had varying developmental delays. EEG was re-examined in 11 cases, of which 8 were normal, and 3 were abnormal. Treatments included intramuscular injections of vitamin B12, L-carnitine, betaine, folic acid, and oral antiepileptic therapy. Acute treatment included anti-infective, blood transfusion, fluid replacement, and correcting acidosis. The other treatments included low-protein diets and special formula milk powder.
Conclusion:
Methylmalonic acidemia can affect the central nervous system, leading to structural changes or abnormal signals on brain MRI. Metabolic screening and genetic testing help clarify the diagnosis. EEG can reflect changes in brain waves during the acute phase.
Insights
Methylmalonic acidemia (MMA) can cause significant nervous system damage, including brain abnormalities and developmental delays. Early diagnosis through metabolic and genetic testing, along with EEG, is crucial for effective management.
Area of Science:
- Neurology
- Metabolic Disorders
- Pediatrics
Background:
- Methylmalonic acidemia (MMA) is a rare inherited metabolic disorder.
- Nervous system damage can be the primary manifestation of MMA.
- Understanding the specific neurological impacts of MMA is essential for diagnosis and treatment.
Purpose of the Study:
- To investigate the clinical, imaging, and electroencephalogram (EEG) characteristics of MMA.
- To identify the primary neurological manifestations in patients with MMA.
- To correlate clinical findings with neuroimaging and EEG results in MMA.
Main Methods:
- Retrospective analysis of 18 patients diagnosed with MMA and nervous system injury.
- Data collected included clinical symptoms, brain imaging (MRI), and electroencephalogram (EEG) findings.
- Metabolic and genetic testing were used for diagnosis.
Main Results:
- Common clinical symptoms included convulsions, poor feeding, growth retardation, and developmental delay.
- Neuroimaging revealed hydrocephalus (33%), widened extracerebral space (50%), and corpus callosum thinning (27%).
- EEG abnormalities were frequent, including abnormal discharge (67%) and abnormal sleep patterns (72%). Hyperhomocysteinemia was present in 89% of patients.
Conclusions:
- MMA significantly impacts the central nervous system, causing structural brain changes and abnormal MRI signals.
- Metabolic screening and genetic testing are vital for diagnosing MMA.
- EEG is a valuable tool for assessing brain wave activity during acute phases of MMA.
