A 4 year-old male patient was referred to our institution by a dermatologist because of the gradually increasing number of xanthomas on the knees, elbows, and buttocks that first appeared when he was 3 years old. He was born after an uneventful pregnancy and delivery as the second child of apparently non-consanguineous parents. The family history for premature CVD was negative. His early development was normal. Extremely high levels of TC (24.8 mmol/L; 928 mg/dl), LDL-C (21.6 mmol/L; 834 mg/dl), and triglycerides (TGC) (5.0 mmol/L; 443 mg/dl) and low levels of HDL-cholesterol (HDL-C) (0.3 mmol/L; 11.6 mg/dl) were measured at the first exam. Elevated levels of TC and LDL-C were also found in his parents, sister, and daughter (afterward) (). The clinical and biochemical picture suggested the diagnosis of HoFH, which was later confirmed genetically; a previously described homozygous mutation c.1754T>C (p.Ile585Thr) was found in the patient, while both his parents, his sister, and daughter were confirmed to be heterozygotes for the same mutation. Despite treatment with a highly restrictive diet, cholestyramine, statins, and LDL-apheresis (the exact timeline is described in , ), xanthomas extended progressively. At 7 years, increased IMT of the common carotid artery was measured with ultrasound. At 12 years, echocardiographically valvular aortic stenosis and aortic regurgitation were observed. Levels of LDL-C at the time of LDL-apheresis ranged from 2.4 to 11.6 mmol/L (92.8–449 mg/dl) in between treatments. Lp(a) levels ranged from 756 mg/L at the beginning to 135 mg/L after the last treatment. He refused to have apheresis for 3 years, but with psychological support, he continued.\nDue to progressive worsening conditions (valvular aortic stenosis and aortic regurgitation), the patient underwent deceased-donor orthotopic LT when he was 16 years old. There were no intraoperative or postoperative complications. The patient's immunosuppression regimen first consisted of tacrolimus, methylprednisolone, and ursodeoxycholic acid, but the steroid was gradually tapered. Six months after the LT, the patient's xanthomas had regressed, and the TC levels have fallen to 5.2 mmol/L (201 mg/dl). A year and a half after the LT, the TC level was at the lowest value [4.4 mmol/L (170 mg/dl)]. Two years after the LT, an episode of acute rejection developed, which was successfully treated with steroids, and the TC level was measured at 5.1 mmol/L (197 mg/dl).\nEight years after the LT, the patient who was then 24 years old was doing well. The patient had been on maintaining tacrolimus therapy. His cutaneous xanthomas completely resolved. An echocardiogram showed complete regression of aortic stenosis, and his IMT was in the normal range (0.6 mm on both common carotid arteries). His TC and LDL-C levels were 5.4 and 3.9 mmol/L, respectively (209 and 151 mg/dl), and Lp(a) levels were 111 mg/L. His LDL-C levels were lower than the LDL-C levels measured on the same occasion in his parents and sister (). Twelve years after the LT, the PWV velocity was measured with ultrasound, and the values were in the normal range (4.6 ± 0.2 m/s) The RHI was 2.46.\nAfterward, the patient was not responding to the invitations from our clinic for almost 5 years (at that time, he was only seeing his gastroenterologist) and returned for a follow-up visit only in the year 2018, almost 14 years after the LT. The total regression of xanthomas was evident at the last visit. At that point, he was almost 30 years old, employed, and had a child who was scheduled for a later visit at our lipid clinic and was confirmed to be heterozygote for the same mutation. His work was mostly sedentary, and he was not very physically active. In addition, he started smoking. He was still taking tacrolimus, but no antilipemic treatment was prescribed to him after the LT. His TC and LDL-C levels were 7.2 mmol/L (278 mg/dl) and 5.3 mmol/L (205 mg/dl), respectively. In addition, an elevated ApoB level was present (1.48 g/L), while his Lp(a) level was normal (145 mg/L). Furthermore, hsCRP was 2.11 mg/L. His carotid IMT level had increased to 0.90 mm on both carotid arteries (abnormal result for his age) (). He was normotensive (97/67 mmHg), and his BMI was 18 kg/m2. Liver enzyme levels were in the normal range. The HbA1c level was 4.8%, and the fasting insulin level was 4.3 mE/L. The glomerular filtration rate was above 90 ml/min. At the last visit to our lipid clinic, the patient was recommended to start statin treatment (rosuvastatin, 10 mg) and was transitioned to the adult lipid clinic, where his first visit was scheduled in early 2019. At that visit, his TC and LDL-C levels were 7.36 mmol/L (284.6 mg/dl) and 5.9 mmol/L (228.15 mg/dl), respectively.
The patient is a Hispanic female diagnosed with homozygous FH at the age of 3 years old. Prior to diagnosis, she had developed multiple cutaneous xanthomas on her hands, feet, elbows, and knees (Figures , , and ). Furthermore, the patient complained of chest pain during exertion. Prior to treatment, serum cholesterol ranged between 500 mg/dL and 900 mg/dL. When the patient was 3 years old, she was started on rosuvastatin and ezetimibe. The patient's cholesterol level did not improve; serum cholesterol remained between 600 mg/dL and 700 mg/dL, and serum LDL level was 358 mg/dL. Genetic mutational analysis confirmed the diagnosis of homozygous FH and demonstrated a LDL-receptor genetic mutation with a DNA base change from adenine to guanine. The patient's only family history was a cousin who also had been diagnosed with homozygous FH and underwent OLT.\nThe patient's cardiac stress test showed no ischemic changes and echocardiogram demonstrated a normal aortic valve with only a trace amount of aortic regurgitation and mild mitral regurgitation, without aortic stenosis. Bilateral carotid artery ultrasound revealed intimal thickening and noncalcified plaques. Computed tomography angiography demonstrated moderate calcification of the aortic valve annulus; calcium-score screening of the right, left main, left anterior descending, and left circumflex coronary arteries was normal. Additionally, cardiac catheterization showed normal coronary arteries without evidence of stenosis or calcification, but also showed mild aortic supravalvular narrowing. The patient was started on LDL aphaeresis due to the exertional angina.\nDue to the severity of her symptoms and the failure of medical management, the patient was listed for and then underwent OLT at the age of 11 years old. The patient had no intraoperative or postoperative complications and was discharged home one week later. The patient's immunosuppression consisted of tacrolimus and prednisolone. The steroids were tapered post-operatively. Her serum cholesterol level and LDL level at the time of discharge were 192 mg/dL and 141 mg/dL, respectively. The patient remains free from exertional angina and her serum cholesterol and LDL levels remain in the normal range since her last followup at 6 months after OLT.