EP1842 - LBA_ECE_1005 - Homozygous familial hypobetalipoproteinemia with abetalipoproteinemia-like phenotype: a rare multisystemic substrate crisis with negative MTTP sequencing

Abstract

Abetalipoproteinemia (ABL) and Homozygous Familial Hypobetalipoproteinemia (HHBL) are ultra-rare lipid metabolism disorders. While ABL is typically caused by MTTP mutations, HHBL results from codominant APOB mutations. Both lead to a near-complete absence of apolipoprotein B-containing lipoproteins, creating a critical substrate crisis for fat-soluble vitamins and cholesterol, which precipitates hepatic, hematologic, and neuro-ophthalmological dysfunction. A 28-year-old female presented with menstrual irregularities, fatigue, and persistent steatorrhea. Laboratory screening revealed severe hypolipidemia (LDL-C <5 mg/dL). Diagnosis was confirmed by ApoB <20 mg/dL, Vitamin E 2.36 µg/mL (critical deficiency), and Vitamin A 520 ng/mL. Hormonal evaluation showed suppressed Estradiol (26 pg/mL). Peripheral smear demonstrated pathognomonic acanthocytosis. Multidisciplinary screening revealed no irreversible pathologies. Hepatobiliary USG showed hepatomegaly (15.5 cm) with Grade 2 steatosis. Family screening confirmed a familial pattern: the 52-year-old father and 50-year-old mother exhibited significant asymptomatic hypolipoproteinemia (LDL-C: 27.8 and 61 mg/dL, respectively). Although there is no known consanguinity, both parents originate from the same small geographical region (approximately ≤250 000 inhabitants), suggesting a potential founder effect. This profile directs the diagnosis toward HHBL despite the severe phenotype. Genetic Evaluation: Targeted MTTP sequencing detected no pathogenic mutations. Since MTTP defects are a regulatory prerequisite for official orphan drug access (eg, Lomitapide), the patient was ineligible for such targeted therapies. To explore the underlying pathology explaining this favorable clinical course, an expanded genetic panel is currently pending. Management involved a strict Low-LCT diet supplemented with Medium-Chain Triglyceride (MCT) oil. Initially, high-dose oral Vitamin E (400 IU 2 × 3) and Vitamin A (30 000 IU 1 × 3) were administered. The high cost of orphan drugs and the non-orphan status of MCT oil posed significant therapeutic barriers. Due to clinical stabilization and financial constraints, treatment was optimized to daily maintenance doses (1 × 1), aligning with state-covered insurance limits. This case underscores the challenges in drug access when canonical markers are absent. Aggressive ADEK supplementation remains the gold standard for stabilizing this phenotype, even when advanced pharmacological options are inaccessible.