Abetalipoproteinemia with angioid streaks, choroidal neovascularization, atrophy, and extracellular deposits revealed by multimodal retinal imaging.

PURPOSE: Abetalipoproteinemia (ABL, MIM 200,100) is a rare autosomal recessive disorder caused by nonfunctional microsomal triglyceride transfer protein leading to absence of apolipoprotein B-containing lipoproteins in plasma and a retinitis pigmentosa-like fundus. The MTTP gene is expressed in retinal pigment epithelium (RPE) and ganglion cells of the human retina. Understanding ABL pathophysiology would benefit from new cellular-level clinical imaging of affected retinas. METHODS: We report multimodal retinal imaging in two patients with ABL. Case 1 (67-year-old woman) exhibited a bilateral decline of vision due to choroidal neovascularization (CNV) associated with angioid streaks and calcified Bruch membrane. Optical coherence tomography were consistent with basal laminar deposits and subretinal drusenoid deposits (SDD). RESULTS: Case 2 (46-year-old woman) exhibited unusual hyperpigmentation at the right fovea with count-fingers vision and a relatively unremarkable left fundus with 20/30 vision. The left eye exhibited the presence of nodular drusen and SDD and the absence of macular xanthophyll pigments. CONCLUSION: We propose that mutated MTTP within the retina may contribute to ABL retinopathy in addition to systemic deficiencies of fat-soluble vitamins. This concept is supported by a new mouse model with RPE-specific MTTP deficiency and a retinal degeneration phenotype. The observed range of human pathology, including angioid streaks, underscores the need for continued monitoring in adulthood, especially for CNV, a treatable condition.

Enhanced recovery after surgery: Preoperative carbohydrate loading and insulin management in type 2 diabetes.

We assessed our institutional practice of individualized insulin dosing for patients with type 2 diabetes receiving preoperative carbohydrate loading (CHO-L) within an enhanced recovery after surgery (ERAS®) protocol. Patients enrolled in an ERAS® protocol with concomitant type 2 diabetes received rapid acting insulin (Novolog®[insulin aspart]) prior to 50 g CHO-L on the day of surgery. Following CHO-L and the administration of insulin, no hypoglycemic episodes occurred with preoperative POC glucose values between 6.8 and 12.3 mmol/L (123 and 221 mg/dL). Our experience demonstrates that administering rapid acting insulin prior to CHO-L in patients with type 2 diabetes is feasible and targets the potentially negative influence CHO-L may impose on preoperative glycemia in this population. Important considerations of this approach are highlighted and an insulin dosing algorithm designed for non-specialty providers is suggested.

Guidance for the diagnosis and treatment of hypolipidemia disorders.

The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol and triglyceride, along with malabsorption of fat and fat-soluble vitamins are characteristic features of these diseases. We summarize the genetic basis of these disorders, provide guidance in their diagnosis and suggest treatment regimens including high dose fat-soluble vitamins as therapeutics. A section on preconception counseling and other special considerations pertaining to pregnancy is included. This information may be useful for patients, caregivers, physicians and insurance agencies involved in the management and support of affected individuals.

Ketogenic diets, not for everyone.

BACKGROUND: The adoption of low-carbohydrate diets can lead to weight loss in many patients. However, these now widespread diets also have the potential to exacerbate hypercholesterolemia. OBJECTIVE: The objective of this study is to display the potentially harmful effects of the ketogenic diet on cholesterol levels in patients with or without underlying hyperlipidemia. METHODS: We describe 5 patients who developed marked increases in plasma cholesterol on ketogenic diets and assessed whether they had a well-described underlying genetic hyperlipidemia. RESULTS: Three out of 5 patients had extraordinary increases of blood cholesterol levels to over 500 mg/dL. The other 2 patients more than doubled their low-density lipoprotein cholesterol levels on a ketogenic diet. One patient had an APOE E2/E2 genotype. A higher burden of common genetic polymorphisms was found in 2 patients, with no major mutations found. No potential genetic cause was seen in a fourth patient, and the fifth patient had no genetic testing. Three patients, including the one who was most hypercholesterolemic, had a marked reduction in cholesterol after reverting to a more liberal diet. One refused to change his diet but had a satisfactory low-density lipoprotein cholesterol reduction on ezetimibe. CONCLUSION: These cases should serve as a caution that high-fat low-carbohydrate diets have the potential to exacerbate or cause hypercholesterolemia in patients with or without underlying genetic hyperlipidemia.