High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolism.

Biallelic pathogenic variants of the Sar1b gene cause chylomicron retention disease (CRD) whose central phenotype is the inability to secrete chylomicrons. Patients with CRD experience numerous clinical symptoms such as gastrointestinal, hepatic, neuromuscular, ophthalmic, and cardiological abnormalities. Recently, the production of mice expressing either a targeted deletion or mutation of Sar1b recapitulated biochemical and gastrointestinal defects associated with CRD. The present study was conducted to better understand little-known aspects of Sar1b mutations, including mouse embryonic development, lipid profile, and lipoprotein composition in response to high-fat diet, gut and liver cholesterol metabolism, sex-specific effects, and genotype-phenotype differences. Sar1b deletion and mutation produce a lethal phenotype in homozygous mice, which display intestinal lipid accumulation without any gross morphological abnormalities. On high-fat diet, mutant mice exhibit more marked abnormalities in body composition, adipose tissue and liver weight, plasma cholesterol, non-HDL cholesterol and polyunsaturated fatty acids than those on the regular Chow diet. Divergences were also noted in lipoprotein lipid composition, lipid ratios (serving as indices of particle size) and lipoprotein-apolipoprotein distribution. Sar1b defects significantly reduce gut cholesterol accumulation while altering key players in cholesterol metabolism. Noteworthy, variations were observed between males and females, and between Sar1b deletion and mutation phenotypes. Overall, mutant animal findings reveal the importance of Sar1b in several biochemical, metabolic and developmental processes.

Pathophysiology and Management of Hyperoxaluria and Oxalate Nephropathy: A Review.

Hyperoxaluria results from either inherited disorders of glyoxylate metabolism leading to hepatic oxalate overproduction (primary hyperoxaluria), or increased intestinal oxalate absorption (secondary hyperoxaluria). Hyperoxaluria may lead to urinary supersaturation of calcium oxalate and crystal formation, causing urolithiasis and deposition of calcium oxalate crystals in the kidney parenchyma, a condition termed oxalate nephropathy. Considerable progress has been made in the understanding of pathophysiological mechanisms leading to hyperoxaluria and oxalate nephropathy, whose diagnosis is frequently delayed and prognosis too often poor. Fortunately, novel promising targeted therapeutic approaches are on the horizon in patients with primary hyperoxaluria. Patients with secondary hyperoxaluria frequently have long-standing hyperoxaluria-enabling conditions, a fact suggesting the role of triggers of acute kidney injury such as dehydration. Current standard of care in these patients includes management of the underlying cause, high fluid intake, and use of calcium supplements. Overall, prompt recognition of hyperoxaluria and associated oxalate nephropathy is crucial because optimal management may improve outcomes.

Severe Coagulopathy in a Patient With Short Bowel Syndrome.

BACKGROUND: Short bowel syndrome (SBS) refers to a malabsorptive state caused by extensive resection of the intestinal tract that leads to chronic diarrhea, electrolyte disturbances, and malnutrition. Although relatively uncommon, patients with SBS can present to the emergency department with more serious complications that are potentially life-threatening. Among these complications, coagulopathy secondary to SBS is an underrecognized condition. CASE REPORT: We present a case of severe coagulopathy secondary to vitamin K deficiency in SBS. The patient presented with unexplained coagulopathy and spontaneous bleeding in multiple organs. With a review of surgical history and detailed clinical evaluation, SBS complicated with vitamin K deficiency was diagnosed, and the patient was treated successfully. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When a patient with a history of repeated intestinal surgery presents with diarrhea, malnutrition, or electrolyte abnormalities, emergency physicians should suspect SBS. Among complications of SBS, vitamin K deficiency is a rare but serious cause of unexplained coagulopathy presenting to the emergency department. Understanding the pathophysiology of SBS facilitates early identification of complications and improves patient outcomes.

Practical guide to exocrine pancreatic insufficiency - Breaking the myths.

BACKGROUND: Exocrine pancreatic insufficiency (EPI) is characterized by a deficiency of exocrine pancreatic enzymes, resulting in malabsorption. Numerous conditions account for the etiology of EPI, with the most common being diseases of the pancreatic parenchyma including chronic pancreatitis, cystic fibrosis, and a history of extensive necrotizing acute pancreatitis. Treatment for EPI includes dietary management, lifestyle changes (i.e., decrease in alcohol consumption and smoking cessation), and pancreatic enzyme replacement therapy. DISCUSSION: Many diagnostic tests are available to diagnose EPI, however, the criteria of choice remain unclear and the causes for a false-positive test are not yet understood. Despite multiple studies on the treatment of EPI using exogenous pancreatic enzymes, there remains confusion amongst medical practitioners with regard to the best approach to diagnose EPI, as well as dosing and administration of pancreatic enzymes. Appropriate use of diagnostics and treatment approaches using pancreatic enzymes in EPI is essential for patients. This opinion piece aims to address the existing myths, remove the current confusion, and function as a practical guide to the diagnosis and treatment of EPI.

Insights from human congenital disorders of intestinal lipid metabolism.

The intestine must challenge the profuse daily flux of dietary fat that serves as a vital source of energy and as an essential component of cell membranes. The fat absorption process takes place in a series of orderly and interrelated steps, including the uptake and translocation of lipolytic products from the brush border membrane to the endoplasmic reticulum, lipid esterification, Apo synthesis, and ultimately the packaging of lipid and Apo components into chylomicrons (CMs). Deciphering inherited disorders of intracellular CM elaboration afforded new insight into the key functions of crucial intracellular proteins, such as Apo B, microsomal TG transfer protein, and Sar1b GTPase, the defects of which lead to hypobetalipoproteinemia, abetalipoproteinemia, and CM retention disease, respectively. These "experiments of nature" are characterized by fat malabsorption, steatorrhea, failure to thrive, low plasma levels of TGs and cholesterol, and deficiency of liposoluble vitamins and essential FAs. After summarizing and discussing the functions and regulation of these proteins for reader's comprehension, the current review focuses on their specific roles in malabsorptions and dyslipidemia-related intestinal fat hyperabsorption while dissecting the spectrum of clinical manifestations and managements. The influence of newly discovered proteins (proprotein convertase subtilisin/kexin type 9 and angiopoietin-like 3 protein) on fat absorption has also been provided. Finally, it is stressed how the overexpression or polymorphism status of the critical intracellular proteins promotes dyslipidemia and cardiometabolic disorders.

Fat malabsorption in critical illness.

Malnutrition in critical illness is common and is associated with significant increases in adverse outcomes. A hypermetabolic state and underfeeding both contribute to the incidence of malnutrition. Malabsorption caused by critical illness is also an important contributor to the development of malnutrition. The early provision of enteral nutrition is associated with improved outcomes. Strategies for nutrition therapy must be informed by the alterations in absorption of macronutrients present in these patients. The following review examines alterations in fat metabolism during critical illness, and its consequences to overall nutrition status. Critical illness, as well as the sequalae of common medical interventions, may lead to alterations in the mechanical and chemical processes by which fat is digested and absorbed. Mechanical alterations include delayed gastric emptying and changes to the normal gut transit time. Pharmacologic interventions aimed at reducing these impacts may themselves, negatively affect efficient fat absorption. Exocrine pancreatic insufficiency can also occur in critical illness and may be underappreciated as a cause of fat malabsorption. Dysfunction of the gut lymphatics has been proposed as a contributing factor to fat malabsorption, and additional work is needed to better describe and quantify those effects. Achieving optimal outcomes for nutrition therapy requires recognition of these alterations in fat digestion.

Fat digestion and absorption: Normal physiology and pathophysiology of malabsorption, including diagnostic testing.

Fat digestion and absorption play crucial roles in maintaining energy homeostasis and supporting essential physiological functions. The initial stage of fat digestion occurs in the stomach, where gastric lipase begins the hydrolysis of triglycerides. However, most fat digestion takes place in the small intestine via pancreatic enzymes and bile salts. Emulsification of fat by bile acids facilitates enzymatic action, breaking down triglycerides into free fatty acids and monoglycerides, which are then able to be absorbed by enterocytes. Fat malabsorption can result from various underlying conditions, such as exocrine pancreatic insufficiency, bile acid disorders, or intestinal diseases. The clinical manifestations of fat malabsorption include steatorrhea, malnutrition, and deficiencies of fat-soluble vitamins. Diagnostic approaches involve assessing fecal fat levels, imaging studies, and various functional tests to identify the specific etiology. This review article will describe the normal physiologic process of fat digestion and absorption and discuss various pathophysiology that can lead to fat malabsorption within the gastrointestinal tract as well as their respective diagnostic testing modalities. Effective digestion of fat is essential for overall health, because it allows for absorption of many essential nutrients, plays an integral role in cellular and structural function, and supplies energy to the body. When this is dysfunctional, disorders of malabsorption can occur. This article will give a brief overview of the physiologic process of fat digestion and absorption in healthy individuals as well as review important pathophysiology that can lead to fat malabsorption within the gastrointestinal tract and current diagnostic testing modalities.

Intestinal Oxalate Absorption, Enteric Hyperoxaluria, and Risk of Urinary Stone Formation in Patients with Crohn's Disease.

Nephrolithiasis is a common urologic manifestation of Crohn's disease. The purpose of this study was to investigate the clinical characteristics, intestinal oxalate absorption, and risk factors for urinary stone formation in these patients. In total, 27 patients with Crohn's disease and 27 healthy subjects were included in the present study. Anthropometric, clinical, and 24 h urinary parameters were determined, and the [13C2]oxalate absorption test was performed. Among all patients, 18 had undergone ileal resection, 9 of whom had a history of urinary stones. Compared to healthy controls, the urinary excretion values of calcium, magnesium, potassium, sulfate, creatinine, and citrate were significantly lower in patients with Crohn's disease. Intestinal oxalate absorption, the fractional and 24 h urinary oxalate excretion, and the risk of calcium oxalate stone formation were significantly higher in patients with urolithiasis than in patients without urolithiasis or in healthy controls. Regardless of the group, between 83% and 96% of the [13C2]oxalate was detected in the urine within the first 12 h after ingestion. The length of ileum resection correlated significantly with the intestinal absorption and urinary excretion of oxalate. These findings suggest that enteric hyperoxaluria can be attributed to the hyperabsorption of oxalate following extensive ileal resection. Oral supplementation of calcium and magnesium, as well as alkali citrate therapy, should be considered as treatment options for urolithiasis.

Fat malabsorption in short bowel syndrome: A review of pathophysiology and management.

Fat malabsorption is central to the pathophysiology of short bowel syndrome (SBS). It occurs in patients with insufficient intestinal surface area and/or function to maintain metabolic and growth demands. Rapid intestinal transit and impaired bile acid recycling further contribute to fat malabsorption. A significant portion of patients require parenteral nutrition (PN) for their survival but may develop sepsis and liver dysfunction as a result. Despite advancements in the treatment of SBS, fat malabsorption remains a chronic issue for this vulnerable patient population. Peer-reviewed literature was assessed on the topic of fat malabsorption in SBS. Current management of patients with SBS involves dietary considerations, PN management, antidiarrheals, glucagon-like peptide 2 agonists, and multidisciplinary teams. Clinical trials have focused on improving intestinal fat absorption by facilitating fat digestion with pancreatic enzymes. Targeting fat malabsorption in SBS is a potential pathway to improving lifestyle and reducing morbidity and mortality in this rare disease.

Cystic fibrosis and fat malabsorption: Pathophysiology of the cystic fibrosis gastrointestinal tract and the impact of highly effective CFTR modulator therapy.

Cystic fibrosis (CF) is a progressive, genetic, multi-organ disease affecting the respiratory, digestive, endocrine, and reproductive systems. CF can affect any aspect of the gastrointestinal (GI) tract, including the esophagus, stomach, small intestine, colon, pancreas, liver, and gall bladder. GI pathophysiology associated with CF results from CF membrane conductance regulator (CFTR) dysfunction. The majority of people with CF (pwCF) experience exocrine pancreatic insufficiency resulting in malabsorption of nutrients and malnutrition. Additionally, other factors can cause or worsen fat malabsorption, including the potential for short gut syndrome with a history of meconium ileus, hepatobiliary diseases, and disrupted intraluminal factors, such as inadequate bile salts, abnormal pH, intestinal microbiome changes, and small intestinal bacterial overgrowth. Signs and symptoms associated with fat malabsorption, such as abdominal pain, bloating, malodorous flatus, gastroesophageal reflux, nausea, anorexia, steatorrhea, constipation, and distal intestinal obstruction syndrome, are seen in pwCF despite the use of pancreatic enzyme replacement therapy. Given the association of poor nutrition status with lung function decline and increased mortality, aggressive nutrition support is essential in CF care to optimize growth in children and to achieve and maintain a healthy body mass index in adults. The introduction of highly effective CFTR modulator therapy and other advances in CF care have profoundly changed the course of CF management. However, GI symptoms in some pwCF may persist. The use of current knowledge of the pathophysiology of the CF GI tract as well as appropriate, individualized management of GI symptoms continue to be integral components of care for pwCF.

Nyctalopia and Xerophthalmia in a Patient With Crohn's Induced Vitamin A Deficiency.

The vitamin A derivative, retinal, plays a pivotal role in scotopic and color vision. Although vitamin A deficiency (VAD) presents as a common cause of preventable blindness in areas with poor access to foods rich in vitamin A, it is uncommon in developed countries. We present a 56-year-old male with a history of Crohn's disease and pancreatitis who was referred to our ophthalmology office by optometry for severe dry eyes. He complained of a two-year history of constant blurred vision and nyctalopia. He stated that "images just appear dark." Examination demonstrated mildly decreased visual acuity with severe ocular surface disease and characteristic Bitot's spots in both eyes. Based on the patient's history and physical, a diagnosis of xerophthalmia in the setting of VAD was made. The patient was referred to his internist, he then underwent further evaluation and treatment with vitamin A intramuscular injections post-diagnosis.  This case illustrates the potential for VAD secondary to malabsorption from Crohn's disease and the importance of taking a full patient history so systemic causes of ophthalmic symptoms may be promptly identified and treated. VAD is extremely rare in the United States, however, patients at risk for VAD may benefit from regular vitamin A level checks and ophthalmologic evaluation.

Pathophysiology and Treatment of Enteric Hyperoxaluria.

Enteric hyperoxaluria is a distinct entity that can occur as a result of a diverse set of gastrointestinal disorders that promote fat malabsorption. This, in turn, leads to excess absorption of dietary oxalate and increased urinary oxalate excretion. Hyperoxaluria increases the risk of kidney stones and, in more severe cases, CKD and even kidney failure. The prevalence of enteric hyperoxaluria has increased over recent decades, largely because of the increased use of malabsorptive bariatric surgical procedures for medically complicated obesity. This systematic review of enteric hyperoxaluria was completed as part of a Kidney Health Initiative-sponsored project to describe enteric hyperoxaluria pathophysiology, causes, outcomes, and therapies. Current therapeutic options are limited to correcting the underlying gastrointestinal disorder, intensive dietary modifications, and use of calcium salts to bind oxalate in the gut. Evidence for the effect of these treatments on clinically significant outcomes, including kidney stone events or CKD, is currently lacking. Thus, further research is needed to better define the precise factors that influence risk of adverse outcomes, the long-term efficacy of available treatment strategies, and to develop new therapeutic approaches.

Sexually dimorphic response of mice to the Western-style diet caused by deficiency of fatty acid binding protein 6 (Fabp6).

Bile acids are natural detergents that aid in the absorption of dietary lipids. Fatty acid binding protein 6 (Fabp6) is a component of the bile acid recovery system that operates in the small intestine. The aim of this study was to determine if Fabp6 deficiency causes dietary fat malabsorption. Wild-type and Fabp6-deficient mice were fed a Western-style diet (WSD) or a reference low-fat diet (LFD) for 10 weeks. The body weight gain, bile acid excretion, fat excretion, energy metabolism, and major gut microbial phyla of the mice were assessed at the end of the controlled diet period. Fabp6-/- mice exhibited enhanced excretion of both bile acids and fat on the WSD but not on the LFD diet. Paradoxically, male Fabp6-/- mice, but not female Fabp6-/- mice, had greater adiposity despite increased fat excretion. Analysis of energy intake and of expenditure by indirect calorimetry revealed sex differences in physical activity level and respiratory quotient, but these did not account for the enhanced adiposity displayed by male Fabp6-/- mice. Analysis of stool DNA showed sex-specific changes in the abundance of major phyla of bacteria in response to Fabp6 deficiency and WSD feeding. The results obtained indicate that the malabsorption of bile acids that occurs in Fabp6-/- mice is associated with dietary fat malabsorption on the high-fat diet but not on the low-fat diet. The WSD induced a sexually dimorphic increase in adiposity displayed by Fabp6-/- mice and sexually distinct pattern of change in gut microbiota composition.

Fifty Years With a Brooke Ileostomy: An Autobiographical Case Report.

Permanent Brooke ileostomy continues to be a treatment option for selected patients with inflammatory bowel disease and cancer. This case report describes the author's 50-year experience living with Crohn's disease and a Brooke ileostomy, including the psychosocial and dietary adaptations required and the management of common complications such as peri-stomal irritant dermatitis, food blockage, and acute infectious diarrhea. Cross-sectional studies indicate that the quality of life with an ileostomy is usually good, but adaptation to an ileostomy is a life-long process.

Exocrine pancreatic insufficiency related fat malabsorption and its association with autonomic neuropathy in Asian Indians with type 2 diabetes mellitus.

BACKGROUND AND AIMS: We aimed to estimate the prevalence of exocrine pancreatic insufficiency (EPI) related fat malabsorption & to correlate it with measures of autonomic neuropathy in patients with T2DM from India. METHODS: Patients with T2DM (cases; n = 118) and normo-glycaemic individuals (controls; n = 82) underwent anthropometry and biochemical evaluation at baseline. The 72-hours fecal fat excretion was estimated by the Van de Kamer's titration method. Autonomic neuropathy was evaluated using an automated analyzer. RESULTS: The prevalence of EPI related fat malabsorption in cases was 45% (n = 53; 72 hours mean fecal fat level = 22.7 ± 5.6 g/day). Dysfunctions in the parasympathetic nervous system (PNS; 86.7%; p < 0.05), sympathetic nervous system (SNS; 92.4%; p < 0.05), and both; PNS + SNS (83.1%; p < 0.05) were significant. Amongst measures of PNS dysfunction, there was a significantly higher percentage of abnormal expiration: inspiration ratio (45.3%) and the 30:15 ratio (84.9%) (p < 0.05) in patients with T2DM and EPI related fat malabsorption. CONCLUSION: In this cross-sectional cohort of Asian Indian patients with T2DM (n = 118), EPI related fat malabsorption correlates significantly with autonomic dysfunction in patients with T2DM. However, these preliminary data need to confirmed in trials with more robust design.

Etiologies, Clinical Features, and Outcome of Oxalate Nephropathy.

BACKGROUND: Oxalate nephropathy is a potentially underestimated cause of kidney failure characterized by massive deposition of calcium oxalate crystals in the renal parenchyma. The prevalence and modes of presentation of this entity are ill-defined. METHODS: Here we report on the largest consecutive series of cases of adult oxalate nephropathy diagnosed on native kidney biopsies from January 2010 to December 2018 in the UCLouvain Kidney Disease Network. RESULTS: We screened 2265 native kidney biopsies and identified 22 cases (1%) of oxalate nephropathy. Patients had a mean age at diagnosis of 61 years (±20) and presented either with acute on chronic kidney disease (CKD) (62%) or with acute kidney injury (AKI) (38%). Mean serum creatinine at biopsy was 8.0 ± 4.5 mg/dl. Kidney biopsies showed abundant calcium oxalate crystal deposits, associated with acute interstitial nephritis and tubular necrosis, and variable degrees of interstitial fibrosis and tubular atrophy. Chronic pancreatitis and gastric bypass were the most common causes of oxalate nephropathy (48%). During a mean follow-up of 29 months, half of the patients (52%) progressed to kidney failure, all within the month following diagnosis. Higher serum creatinine level at presentation and interstitial fibrosis and tubular atrophy score were associated with progression to kidney failure. CONCLUSION: Oxalate nephropathy is the cause of kidney disease in 1% of consecutive native kidney biopsies and typically presents as acute on CKD or AKI. The prognosis of the disease is poor, with a high rate of kidney failure within the first month after the diagnosis.

Atypical Cystic Fibrosis: Diagnosis at the Age of 57 Years.

Cystic fibrosis (CF) is an autosomal recessive, multi-organ disorder found predominantly among Caucasians. It classically presents in childhood with chronic productive cough, malabsorption causing steatorrhea, and failure to thrive. We present a 75-year-old female diagnosed with CF at the age of 57 years, which highlights the natural history and challenges in the diagnosis of atypical CF, including broadening physicians' respiratory differential diagnosis, limited patient symptoms, and late age of symptom onset.

Chylomicron Retention Disease in A Male Infant: A Rare Case from Pakistan.

Chylomicron retention disease (CMRD), also known as Anderson's disease, is an autosomal recessive condition with a genetic mutation in the secretion associated Ras related GTPase 1B (SAR1B) gene, a protein coding gene. CMRD classically manifests as steatorrhea, vomiting, failure to thrive or abdominal bloating shortly after birth or in childhood. Here, we report a rare case of a 50-day-old male infant who was, at first, overseen as a case of acute gastroenteritis with sepsis owing to the non-specific symptoms i.e. multiple episodes of loose stools with a low-grade fever and failure to thrive, and was managed accordingly. However, the symptoms did not resolve; moreover, the clinical condition deteriorated. Later, lipid profile, clinical presentation and pathological features led to a presumptive diagnosis of CMRD. Our patient showed significant improvement when treated with a trial of medium- and short-chain fatty acids. We conclude that, in resource-restricted countries, a therapeutic trial with the dietary changes is essential to not only prevent the devastating complication but also support the diagnosis.

Postprandial lipid absorption in seven heterozygous carriers of deleterious variants of MTTP in two abetalipoproteinemic families.

BACKGROUND: Abetalipoproteinemia, a recessive disease resulting from deleterious variants in MTTP (microsomal triglyceride transfer protein), is characterized by undetectable concentrations of apolipoprotein B, extremely low levels of low-density lipoprotein cholesterol in the plasma, and a total inability to export apolipoprotein B-containing lipoproteins from both the intestine and the liver. OBJECTIVE: To study lipid absorption after a fat load and liver function in 7 heterozygous relatives from 2 abetalipoproteinemic families, 1 previously unreported. RESULTS: Both patients are compound heterozygotes for p.(Arg540His) and either c.708_709del p.(His236Glnfs*11) or c.1344+3_1344+6del on the MTTP gene. The previously undescribed patient has been followed for 22 years with ultrastructure analyses of both the intestine and the liver. In these 2 families, 5 relatives were heterozygous for p.(Arg540His), 1 for p.(His236Glnfs*11) and 1 for c.1344+3_1344+6del. In 4 heterozygous relatives, the lipid absorption was normal independent of the MTTP variant. In contrast, in 3 of them, the increase in triglyceride levels after fat load was abnormal. These subjects were additionally heterozygous carriers of Asp2213 APOB in-frame deletion, near the cytidine mRNA editing site, which is essential for intestinal apoB48 production. Liver function appeared to be normal in all the heterozygotes except for one who exhibited liver steatosis for unexplained reasons. CONCLUSION: Our study suggests that a single copy of the MTTP gene may be sufficient for human normal lipid absorption, except when associated with an additional APOB gene alteration. The hepatic steatosis reported in 1 patient emphasizes the need for liver function tests in all heterozygotes until the level of risk is established.

Novel mutations of SAR1B gene in four children with chylomicron retention disease.

BACKGROUND: Intestinal lipid malabsorption, resulting from an impaired formation or secretion of chylomicrons and associated with severe hypobetalipoproteinemia (HBL), may be due to biallelic mutations in APOB (homozygous FHBL type-1), MTTP (abetalipoproteinemia), or SAR1B (chylomicron retention disease). OBJECTIVE: We investigated four children, each born from consanguineous parents, presenting with steatorrhea, malnutrition, accumulation of lipids in enterocytes, and severe hypocholesterolemia with an apparent recessive transmission. METHODS: We sequenced a panel of genes whose variants may be associated with HBL. RESULTS: Case 1, a 9-month-old male, was found to be homozygous for a SAR1B variant (c.49 C>T), predicted to encode a truncated Sar1b protein devoid of function (p.Gln17*). Case 2, a 4-year-old male, was found to be homozygous for a SAR1B missense variant [c.409 G>C, p.(Asp137His)], which affects a highly conserved residue close to the Sar1b guanosine recognition site. Case 3, a 6-year-old male, was found to be homozygous for an ∼6 kb deletion of the SAR1B gene, which eliminates exon 2; this deletion causes the loss of the ATG translation initiation codon in the SAR1B mRNA. The same homozygous mutation was found in an 11-month-old child (case 4) who was related to case 3. CONCLUSIONS: We report 4 children with intestinal lipid malabsorption were found to have chylomicron retention disease due to 3 novel variants in the SAR1B gene.