Severe Combined Dyslipidemia With a Complex Genetic Basis: A | Figure 1
Severe Combined Dyslipidemia With a Complex Genetic Basis
A 48-year-old male presented with severe combined dyslipidemia: total cholesterol and TG were 11.5 and 21.4 mmol/L, respectively. He had dyslipidemia since his early 20s, with tuberous xanthomas on his elbows and knees. His body mass index was 42 kg/m2. He also had treated hypertension, mild renal impairment, and a history of gout. He had no history of cardiovascular disease, peripheral arterial disease, or pancreatitis. Multiple medications had been advised including rosuvastatin, ezetimibe, fenofibrate, and alirocumab, but his lipid levels were never adequately controlled.
Genetic Analysis
Targeted next-generation sequencing identified (1) the APOE E2/E2 homozygous genotype classically described with familial dysbetalipoproteinemia; (2) in addition, one APOE E2 allele contained the rare heterozygous missense variant p.G145D, previously termed apo E-Bethesda; (3) a rare heterozygous APOC2 nonsense variant p.Q92X; and (4) a high polygenic risk score for TG levels (16 out of 28 TG-raising alleles) at the 82nd percentile for age and sex.
More about this case
Resolved Verified literature Rare Common presentation
Case Example: 24-Year-Old Patient with Osteogenesis Imperfecta
A 24-year-old patient presented with chronic low back pain following a low-energy trauma having occurred while practicing sports. Past medical history was significant for a Colles fracture, and two childhood finger fractures. He did not consider the occurrences unusual or alarming and did not pursue further evaluation at that time. Otherwise, the patient was healthy with no history of smoking or drinking alcohol.
After a recent vertebral compression fracture and a second Colles fracture, he became worried, and sought medical care because of continued pain and functional loss. The patient's family history was also remarkable for osteoporosis and recurrent fractures in several relatives. On physical examination, the patient was below average height, and blue-gray sclera were observed. He had mild scoliosis and local tenderness in the lumbar spine.
Imaging showed a compression fracture at L1 and severe osteoporosis for his age. Laboratory investigation ruled out a secondary cause of bone fragility. He was evaluated by a genetic specialist which led to a diagnosis of osteogenesis imperfecta. Family members were provided with genetic counseling. This case highlights the possibility of adult osteogenesis imperfecta presenting late when the patient is otherwise well and does not seek medical attention until multiple fractures occur.
Case Example: 19-Day-Old Neonate with Chronic Granulomatous Disease
This case report underlines the diagnostic and therapeutic dilemmas in a 19-day-old neonate who had presented with features suggestive of chronic granulomatous disease (CGD). The baby had a history of fever, lethargy, and masses on the skin, for which an extensive diagnostic workup was needed to rule out infective etiology given no improvement with initial empiric therapy.
Laboratory investigations, including imaging and genetic studies, confirmed the diagnosis of CGD. In addition to the very early manifestation of disease, which is quite rare, our case emphasizes the importance of maintaining a high index of suspicion for immunodeficiency disorders in neonates with severe infections.
Case Example: Dominant Negative Mechanism in 46,XY Child with Lipoid Congenital Adrenal Hyperplasia
Case Description: Lipoid congenital adrenal hyperplasia (LCAH) is typically inherited as an autosomal recessive condition. This report discusses a 46,XY child with a novel heterozygous intronic variant in STAR resulting in LCAH with an attenuated genital phenotype. The patient presented with neonatal hypoglycemia and had descended testes with a fused scrotum and small phallus. Evaluation revealed primary adrenal insufficiency with deficiencies of cortisol, aldosterone, and androgens.
Case Example: 41-Year-Old Man with Diffuse Cutaneous Mastocytosis
A 41-year-old man presented with a 1-year history of multiple widespread yellowish, ovoid papular eruptions. Lesions were in different evolutionary stages. The disease was stabilized with the use of antihistamines. Diffuse cutaneous mastocytosis pseudoxanthomatous variant is an extremely rare form of cutaneous mastocytosis, especially with such acute onset in an adult.
Additional Case Examples
Case Example: 52-Year-Old Man with Chest Pain
A 52-year-old man presented with a 20-minute history of chest pain radiating to the left shoulder and neck, associated with dyspnea and diaphoresis.
Case Example: 28-Year-Old Woman with Pruritus
A 28-year-old woman presented with a 3-day history of intense pruritus over the lower back after exposure to dogs.
Case Example: 4-Month-Old Male with Skin Lesions
A 4-month-old male infant presented with skin lesions localized to the chin for the past 3 days.