Acetaminophen treatment in children and adults with spinal muscular atrophy: a lower tolerance and higher risk of hepatotoxicity.

Acute liver failure has been reported sporadically in patients with spinal muscular atrophy (SMA) and other neuromuscular disorders with low skeletal muscle mass receiving recommended dosages of acetaminophen. It is suggested that low skeletal muscle mass may add to the risk of toxicity. We aimed to describe the pharmacokinetics and safety of acetaminophen in patients with SMA. We analyzed acetaminophen metabolites and liver biomarkers in plasma from SMA patients and healthy controls (HC) every hour for six or eight hours on day 1 and day 3 of treatment with therapeutic doses of acetaminophen. Twelve patients with SMA (six adults and six children) and 11 HC participated in the study. Adult patients with SMA had significantly lower clearance of acetaminophen compared to HC (14.1 L/h vs. 21.5 L/h). Formation clearance of acetaminophen metabolites, glucuronide, sulfate, and oxidative metabolites were two-fold lower in the patients compared to HC. The liver transaminases and microRNAs increased nine-fold in one adult SMA patient after two days of treatment. The other patients and HC did not develop abnormal liver biomarkers. In this study, patients with SMA had lower clearance and slower metabolism of acetaminophen, and one patient developed liver involvement. We recommend giving 15 mg/kg/dose to SMA adults (with a maximum of 4000 mg/day) and monitoring standard liver biomarkers 48 h after first-time treatment of acetaminophen.

Low skeletal muscle mass and liver fibrosis in children with cerebral palsy.

The purpose of the study was to conduct a nutritional and metabolic assessment of children with cerebral palsy, including an investigation of liver status, body composition, and bone mineral density. In this cross-sectional study we included 22 children with cerebral palsy. By using ultrasound, transient elastography, dual x-ray absorptiometry (DXA) scan, blood samples, anthropometric measurements, and a three-day diet registration, the nutritional and metabolic status was evaluated. Liver fibrosis and steatosis were found in four patients (18.2%), all with severe motor impairments, low skeletal muscle mass, and epilepsy. All patients with liver involvement had normal liver-related blood samples. Decreased bone mineral density was found in 26.3%, and 91.0% had low skeletal muscle mass. Fat mass and muscle mass were significantly lower in the patients with severe motor impairments compared to the patients with less severe motor impairments. Within the children classified as 'underweight' or 'normal' according to body mass index, body fat determined by DXA scan was normal or high in 50% of these patients. CONCLUSIONS: This study is the first to report liver fibrosis and steatosis in children with cerebral palsy. Possible causes of liver fibrosis and/or steatosis are altered body composition with low skeletal muscle mass, decreased mobility and medical drug intake. Further investigations of liver involvement and risk factors are needed. WHAT IS KNOWN: • Children and adolescents with cerebral palsy are at risk of malnutrition and altered body composition, both of which can lead to fatty liver disease. • It is unknown whether children with cerebral palsy are at increased risk of metabolic disturbances such as fatty liver disease. WHAT IS NEW: • Altered body composition and low skeletal muscle mass, regardless of ambulation is present in 91% of the children with cerebral palsy. • Liver fibrosis and/or steatosis were found in 18.2% of the patients. Possible causes are altered body composition, decreased mobility and medical drug intake.

Metabolic assessment in children with neuromuscular disorders shows risk of liver enlargement, steatosis and fibrosis.

AIM: The aim of this study was to conduct a metabolic and nutritional assessment of children with neuromuscular disorders, including the investigation of the liver and bone mineral density. METHODS: In this observational study, we included 44 children with neuromuscular disorders. The nutritional status, bone health and liver were assessed by ultrasound, transient elastography, dual X-ray absorptiometry scan, blood samples, anthropometric measurements and 3-day diet registration. RESULTS: Liver involvement was found in 31.0%: liver enlargement in 7.1%, steatosis in 4.8%, fibrosis in 14.3% and liver enlargement together with steatosis or fibrosis was found in 4.8%. These changes were found in 9/23 patients with Duchenne muscular dystrophy, 4/9 patients with spinal muscular atrophy type II and 0/12 patients with other neuromuscular diagnoses. Low bone mineral density was found in 44.0% of the patients, though the majority used daily vitamin D and calcium supplements. Vitamin D insufficiency or deficiency was found in 22.6%. CONCLUSION: The metabolic assessment in children with neuromuscular disorders shows an increased risk of liver enlargement, steatosis and fibrosis. Possible causes are obesity, decreased mobility, low skeletal muscle mass and for a subgroup the use of glucocorticoids. The findings suggest that monitoring liver function should be part of the nutritional assessment in patients with neuromuscular disorders.