👤 Hatice Mutlu

APOB-related familial hypobetalipoproteinemia (APOB-FHBL), the most common form of primary hypobetalipoproteinemia, often leaves heterozygous patients asymptomatic. This study aims to provide updated insights into the complications observed in heterozygous and homozygous APOB-FHBL patients. A retrospective analysis was conducted on 15 patients (53.3% female) from 7 families diagnosed with FHBL and followed in a metabolic clinic. Demographic, laboratory, clinical, and genetic data were reviewed. Patients were followed for an average of 4.5 ± 4.1 years. The median levels were as follows: low-density lipoprotein cholesterol (LDL-C; 25.7 ± 10.5 mg/dL), apolipoprotein B (ApoB; 0.3 ± 0.1 g/L), aspartate aminotransferase (AST; 40.1 ± 22.5 U/L), alanine aminotransferase (ALT; 43.0 ± 38.3 U/L), and alpha feto-protein (1.3 ± 0.7 ng/mL). Elevated AST and ALT levels were observed in 20.0% and 26.7% of cases, respectively. Vitamin E deficiency was identified in 26.7%, vitamin A deficiency in 13.3%, and vitamin D insufficiency in 66.7% of cases. Liver ultrasonography revealed hepatosteatosis in 73.3% of patients. Additionally, the study identified 5 novel APOB gene variants. Among the families, 3 had members who died due to complications related to viral infections (COVID-19, hepatitis B virus) or hepatocellular carcinoma (HCC) resulting from chronic liver disease. Patients with elevated transaminase levels or hepatosteatosis should undergo a lipid profile assessment. LDL-C levels below 50 mg/dL require further evaluation, including ApoB and fat-soluble vitamin levels. Monoallelic APOB variants are linked to poor outcomes due to deficiencies in vitamins A, E, and D, as well as an increased risk of HCC. Early recognition and regular monitoring are essential for the effective management of APOB-FHBL patients. Show less

Tricho-rhino-phalangeal syndrome (TRPS) is a rare, autosomal dominant disorder characterized by typical craniofacial features, ectodermal and skeletal findings. TRPS type 1 (TRPS1) is caused by pathogenic variations in the TRPS1 gene, which relates to the vast majority of cases. TRPS type 2 (TRPS2) is a contiguous gene deletion syndrome involving loss of functional copies of the TRPS1, RAD21, and EXT1. Herein, we reported the clinical and genetic spectrum of seven TRPS patients with a novel variant. We also reviewed the musculoskeletal and radiological findings in the literature. Seven Turkish patients (three female, four male) from five unrelated families aged between 7 to 48 years were evaluated. The clinical diagnosis was confirmed by either molecular karyotyping or TRPS1 sequencing analysis via next-generation sequencing. Both TRPS1 and TRPS2 patients had some common distinctive facial features and skeletal findings. All patients had a bulbous nose with hypoplastic alae nasi, brachydactyly, short metacarpals and phalanges in variable stages. Low bone mineral density (BMD) was identified in two TRPS2 family members presenting with bone fracture, and growth hormone deficiency was detected in two patients. Skeletal X-ray imaging revealed cone-shaped epiphysis of the phalanges in all, and multiple exostoses were present in three patients. Cerebral hamartoma, menometrorrhagia and long bone cysts were among the new/rare conditions. Three pathogenic variants in TRPS1 were identified in four patients from three families, including a frameshift (c.2445dup, p.Ser816GlufsTer28), one missense (c.2762G > A), and a novel splice site variant (c.2700+3A > G). We also reported a familial inheritance in TRPS2 which is known to be very rare. Our study contributes to the clinical and genetic spectrum of patients with TRPS while also providing a review by comparing with previous cohort studies. Show less