Familial hypobetalipoproteinemia in pediatric patients with fatty liver: an under-recognized cause

Fatty liver is a leading cause of chronic liver disease in children, most often due to metabolic dysfunction-associated steatotic liver disease (MASLD). Fatty liver in lean or younger children may indicate underlying metabolic or genetic disorders, such as familial hypobetalipoproteinemia (FHBL). We examined the importance of considering familial hypobetalipoproteinemia (FHBL) in children presenting with fatty liver.

This case series includes seven patients with FHBL from three families, treated at two medical centers. Clinical, laboratory, imaging, and genetic data were collected from the medical records.

Four patients were male. The mean age at diagnosis was 15.3 years (range: 4-38). All the index patients were children or adolescents presenting with fatty liver. Genetic evaluation revealed biallelic variants in the microsomal triglyceride transfer protein (MTTP) gene in two siblings and heterozygous variants in the apolipoprotein B (APOB) gene in five patients. The mean body mass index was 27 kg/m², and two patients had a BMI above 30 kg/m². The median follow-up (FU) time was 12 months (interquartile range [IQR]: 1-57 months). Liver enzymes were elevated in three patients (range: 50-300 IU/L); median aspartate aminotransferase and alanine aminotransferase levels were 30 IU/L (IQR: 26-40.75) and 32 IU/L (IQR: 24.5-74), respectively. The median triglyceride, low-density lipoprotein, and apolipoprotein B levels were 74 mg/dL (IQR: 62-125), 55.3 mg/dL (IQR: 30-84.5), and 39.5 mg/dL (IQR: 35.2-43), respectively.

FHBL should be considered a potential diagnosis in children with fatty liver and may coexist with other contributing etiologies such as obesity.