ESPE Abstracts

Objective: To describe the clinical characteristics of a child with 21-hydroxylase deficiency (21OHD) combined with familial hypercholesterolemia (FH), who also developed Kawasaki disease (KD), and to follow up over a long period.

Methods: Clinical data of a boy with 21OHD combined with FH were collected. Treatments with hydrocortisone, fludrocortisone, atorvastatin, and ezetimibe were administered, with monitoring of the aforementioned indices and adverse drug reactions.

Results: The patient was diagnosed with elevated 17-OHP during newborn screening. Biochemistry showed potassium 5.36mmol/L, sodium 127mmol/L, TG 1.33mmol/L, TC 5.94mmol/L, LDL-C 4.11mmol/L, ACTH 52pg/ml, cortisol 224nmol/L, testosterone 146ng/dl, progesterone 9.67ng/ml, AND >10ng/ml, 17-OHP 348nmol/L. Genetic sanger sequencing revealed compound heterozygous variations in CYP21A2 gene (c.293-13C>G and c.T113A:p.I38N, heterozygous variation), inherited from the parents, diagnosing "21OHD". Treatment started with oral hydrocortisone 1.1 mg q8h (13 mg/m2) and fludrocortisone 0.1 mg qd. Regular monitoring showed 17-OHP fluctuating between 0.1~11.3nmol/L, testosterone <2.5~22.66ng/dl, and ACTH fluctuating from <5~13pg/ml with normal electrolytes, progesterone and dehydroepiandrosterones. At 1.1 years old, the child developed KD with echocardiography showing "dilation of the left and right coronary arteries." Treatment with IVIG 4g/kg, aspirin, and pamidronate, with gradual symptom recovery. Two weeks later, echocardiography showed small arterial aneurysm formation at the right coronary artery origin, dilation of the left coronary artery, and aspirin and pamidronate were continued orally. Two months later, follow-up showed minor xanthomas on the wrists and ankles, TG 0.91mmol/L, TC 14.56mmol/L, LDL-C 13.00mmol/L, with coronary artery aneurysms regressing and dilation gradually restoring. A low-fat diet continued, and hydrocortisone 1.1 mg tid (8 mg/m2), fludrocortisone 0.1 mg qd were prescribed, along with whole exome sequencing showing LDLR gene heterozygous variation (c.G2389A:p.V797M), diagnosing "FH". With diet control until age 2.6, biochemistry showed TC 11.63 mmol/L, LDL-C 9.64 mmol/L, normal 17-OHP. After approval from the Ethics Committee of Fujian Medical University Fuzhou Children's Hospital and with parental consent, the child was given oral atorvastatin 5 mg, qd, gradually adjusted to atorvastatin 10 mg qd, ezetimibe 5 mg qd, hydrocortisone 2 mg q8h (11.2 mg/m2), and fludrocortisone 0.1 mg qd. Xanthomas regressed compared to before, with biochemistry showing TC 6.29 mmol/L, LDL-C 4.3 mmol/L, without significant AD.

Conclusion: This study reports a child with both 21-OHD and FH, who developed KD during the follow-up. Treatment with atorvastatin and ezetimibe from 2.6 years-old was overall safe. The follow-up findings suggest that high cholesterol levels might reduce the dosage of hydrocortisone needed for 21-OHD, the mechanism of which warrants further study.