Abstract
BACKGROUND: Familial lecithin-cholesterol acyltransferase (LCAT) deficiency and α(0)-thalassemia are rare autosomal recessive disorders. Although both disease-causing genes reside on chromosome 16, their physical distance typically results in independent inheritance in non-consanguineous populations. Co-inheritance of both conditions has not been previously reported. CASE PRESENTATION: A 50-year-old Chinese man with childhood-onset corneal opacity and long-standing anemia presented with 2 months of progressive lower limb edema. Laboratory evaluation revealed nephrotic syndrome and markedly reduced high-density lipoprotein cholesterol (HDL-C). Renal biopsy showed characteristic glomerular lipid deposition, confirming LCAT deficiency. Genetic testing identified a homozygous LCAT mutation (c.355G>C, p.Gly119Arg), with both parents confirmed as heterozygous carriers. The patient had severe microcytic hypochromic anemia that did not fully align with the mild hemolytic anemia typical of LCAT deficiency. Given parental consanguinity, expanded genetic testing revealed co-inheritance of α(0)-thalassemia (HBA: -SEA/αα), explaining the hematological phenotype. OUTCOME: No specific treatment exists for LCAT deficiency. Symptomatic management with angiotensin-converting enzyme inhibitors and diuretics improved edema. The α(0)-thalassemia trait is asymptomatic and requires no intervention; its diagnosis avoided unnecessary iron therapy and the associated risk of iron overload. Long-term follow-up will focus on renal function, proteinuria, lipid profile, and ocular findings. Genetic counseling will also be provided to the patient and their family. CONCLUSION: To our knowledge, this is the first reported case of co-inherited LCAT deficiency and α(0)-thalassemia confirmed by both renal pathology and comprehensive genetic testing. The consanguineous background suggests possible co-transmission of distant recessive variants on the same chromosome. This case highlights the importance of considering coexisting genetic disorders in patients with consanguinity or unexplained multisystem involvement.