Abstract:
Familial hypercholesterolemia is an autosomal hereditary disease defined by an increased
level of low-density lipoprotein cholesterol (LDL-C), which predisposes significant risks for premature
cardiovascular disorders. We present a family trio study: proband, a 13-year-old Kazakh girl with
homozygous familial hypercholesterolemia (HoFH) and her parents. HoFH is much more rare and
severe than a heterozygous form of the disorder. HoFH patients generally present with LDL-C levels
exceeding 13 mmol/L, resulting in early and life-threatening cardiovascular events within the first
decades of life. In cases of neglected treatment, young patients have a risk of death from coronary
diseases before the age of 30. The aim of this research was to identify genetic mutations in the affected
patient and her parents. Genetic testing was necessary due to highly elevated LDL-C levels and the
presence of multiple xanthomas. Targeted next-generation sequencing (NGS) was performed in this
study using the Illumina TruSight cardio panel, which targets 174 genes related to cardiac disorders.
The girl was diagnosed with HoFH based on the results of genetic testing. A biallelic mutation
was observed in exon 3 of the low-density lipoprotein receptor (LDLR): c. 295 G>A (p.Glu99Lys).
Sanger sequencing confirmed that the mutant gene was inherited from both parents. After confirming
the genetic diagnosis of HoFH, the patient was treated with LDL apheresis and statins. This case
report is the first study of HoFH in a pediatric patient from the Central Asian region. Globally, it
emphasizes the need for increased clinical awareness among healthcare providers, as early detection
and intervention are important for improving outcomes, particularly in pediatric patients with this
rare genetic disorder.
