Ophthalmologic evaluation in vitamin-E deficiency: A case report.

A 41-year-old woman has come to our attention complaining of decreased visual acuity and monocular diplopia associated with upper and lower limb hypoesthesia. Malabsorption syndrome with vitamin A and E deficiency developed after a bariatric biliopancreatic diversion. The clinical ophthalmological signs and symptoms improved after oral vitamin supplementation therapy. The past medical history is essential in the case of a patient complaining of visual symptoms compatible with vitamin deficiency in order to detect the cause and to start a prompt therapy to avoid irreversible neurological and visual sequelae. The clinical features of our case closely resemble other cases described in the literature of patients affected by vitamin A and E deficiency secondary to malabsorption syndrome.

Chylomicron retention disease caused by a new pathogenic variant in sar1b protein: a rare case report from Syria.

BACKGROUND: Chylomicron retention disease (Anderson disease) is a result for variant of the SAR1B gene. It is a rare autosomal recessive hereditary disorder with most incidence in infant. It is characterized by lipid malabsorption syndrome with fatty, chronic diarrhea, and growth retardation. CASE PRESENTATION: We report a case of a 19-month Syrian boy who presented with vomiting, growth failure, and chronic, fatty diarrhea. Upper gastrointestinal endoscopy showed whitish appearing duodenal mucosa and small intestinal biopsies revealed steatosis of enterocytes. Genetic testing confirmed chylomicron retention disease with the first description of variant located in the fourth helix of sar1b protein. The patient is treated with nutritional supplements and fat-soluble vitamin supplementation resulting in significant improvement. CONCLUSION: Early endoscopy is recommended in infants with persistent vomiting and failure to thrive due to high suspicion for a disorder of hypocholesterolemia. Early diagnosis and treatment are essential to avoid serious clinical complications, especially neurological impairment.

Imerslund-Grasbeck syndrome in a cross-breed dog.

Imerslund-Gräsbeck syndrome is an autosomal recessive disease reported only in certain pure-breed dogs. An 18-month-old, male neutered beagle cross-breed was presented for evaluation of severe lethargy, progressive weakness and anorexia. Main clinicopathological findings included low body condition score (2.5/9), severe muscle atrophy, several neurological abnormalities, mild normochromic, normocytic, non-regenerative anaemia, severe hypocobalaminemia and mild proteinuria. Extensive diagnostic tests ruled out most of differential diagnoses for the aforementioned clinicopathological abnormalities and genetic evaluation showed that the dog was heterozygous for two previously described mutations affecting the CUBN gene, the beagle and the border collie variants. The dog showed an excellent clinical response to oral cobalamin supplementation with no relapse after 4 months. In conclusion, this case creates awareness that Imerslund-Gräsbeck syndrome should be considered even in mixed-breed dogs with compatible clinical signs and that two different pathogenic CUBN mutations in compound heterozygosity can lead to a typical Imerslund-Gräsbeck syndrome phenotype.

Is Parenteral Levothyroxine Therapy Safe in Intractable Hypothyroidism?

CASE: A 32-year old woman was admitted to the hospital due to intractable hypothyroidism refractory to high dose of oral l-thyroxine therapy. She underwent total thyroidectomy and radioactive iodine therapy due to papillary thyroid cancer. After excluding poor adherence to therapy and malabsorption, levothyroxine absorption test was performed. No response was detected. Transient neurologic symptoms developed during the test. She developed 3 attacks consisting of neurologic symptoms during high dose administration. The patient was considered a case of isolated l-thyroxine malabsorption. She became euthyroid after intramuscular twice weekly l-thyroxine therapy. DISCUSSION: There are a few case reports regarding isolated l-thyroxine. We report successful long term results of twice weekly administered intramuscular l-thyroxine therapy. We also draw attention to neurologic side effects of high dose l-thyroxine therapy.

Vitamin A deficiency due to chronic malabsorption: an ophthalmic manifestation of a systemic condition.

A 47-year-old woman presented with a 4-week history of progressive loss of vision, first manifesting as night blindness. Additionally, the patient reported frequent severe episodes of diarrhoea over the past month. Her medical history included end-stage renal failure for which she was currently on haemodialysis after a failed renal transplant, chronic pancreatitis and autonomic diabetes mellitus. Ophthalmological examination revealed severe bilateral corneal xerosis, bilateral Bitot's spots and inferior ulceration of the right cornea. A diagnosis of xerophthalmia due to vitamin A deficiency was made, most likely due to the presence of small intestinal bacterial overgrowth and the patient's chronic malabsorptive state. Standard management using oral vitamin A tablets was ineffective, resulting in the patient requiring intravenous supplementation. The extent of visual deterioration on presentation and the difficulties encountered managing the patient resulted in the patient's vision failing to improve.

[Two cases with generalized intracranial calcification due to hereditary folate malabsorption and literature review].

Objective: This study aimed to investigate the clinical, biochemical and genetic features of two Chinese children with hereditary folate malabsorption. Method: Clinical features, laboratory examinations, treatment and SLC46A1 gene of two cases were studied. Reports on hereditary folate malabsorption utill September of 2016 were searched and the clinical and genetic characteristics of reported cases were summarized. Result: The two patients presented with megaloblastic anemia from their infant period and seizures, psychomotor retardation and regression. In case1, mean corpuscular volume (MCV) was 100 fl. Serum folate was 9.96 nmol/L. Folate and 5-methylenetetrahydrofolate in cerebrospinal fluid were 0 and 0.01 separately. In case 2, MCV was 93.9 fl. Serum folate was 4.49 nmol/L. The concentration of folate and 5-methylenetetrahydrofolate in cerebrospinal fluid were both zero. On their brain CT, progressive bilateral symmetrical calcification was observed. On their SLC46A1 gene, four mutations were identified. Case 1 had one novel mutation, c. 1238T>C (L413P) and c. 194-195insG (p.Cys66LeufsX99). From Case 2, two reported mutations, c. 1A>T (M1L) and c. 194-195insG (p.Cys66LeufsX99) were identified. The administration of folinic acid (60 to 120 mg per day) was initiated after diagnosis. Clinical improvement and normalized hematologic markers were observed after treatment. Totally 37 cases were reported in reviewed English literature, including 30 cases with mutations on SLC46A1 gene (only one Chinese patient). All the cases had the onset in infancy. The ratio of boys to girls was 1 to 1.5. Main manifestations were characterized by megaloblastic anemia (77%), failure to thrive (50%), diarrhea (27%), psychomotor retardation (63.6%), epilepsy (27%), and infection of respiratory system (45.5%). The concentration of folate in both serum and cerebrospinal fluid was decreased (72.7% and 63.6% respectively). Hypoimmunoglobulinemia accounted for 27.3%. Most of mutations in HFM were distributed between p. 65 and p. 68 (c.194-c.204), mainly due to insertion- or deletion-related frame shifts or generation of stop codons. Oral and parenteral folinic acid treatment was effective. Conclusion: Hereditary folate malabsorption often presented with megaloblastic anemia, abnormalities of digestive and nervous system, and hypoimmunoglobulinemia with recurrent infections. Low level of serum and CSF folate and screening SLC46A1 gene are keys to the etiologic study of the patients. Early supplement with folinic acid is beneficial to the prognosis.

Environmental Enteric Dysfunction and Growth Failure/Stunting in Global Child Health.

Approximately 25% of the world's children aged <5 years have stunted growth, which is associated with increased mortality, cognitive dysfunction, and loss of productivity. Reducing by 40% the number of stunted children is a global target for 2030. The pathogenesis of stunting is poorly understood. Prenatal and postnatal nutritional deficits and enteric and systemic infections clearly contribute, but recent findings implicate a central role for environmental enteric dysfunction (EED), a generalized disturbance of small intestinal structure and function found at a high prevalence in children living under unsanitary conditions. Mechanisms contributing to growth failure in EED include intestinal leakiness and heightened permeability, gut inflammation, dysbiosis and bacterial translocation, systemic inflammation, and nutrient malabsorption. Because EED has multiple causal pathways, approaches to manage it need to be multifaceted. Potential interventions to tackle EED include: (1) reduction of exposure to feces and contact with animals through programs such as improved water, sanitation, and hygiene; (2) breastfeeding and enhanced dietary diversity; (3) probiotics and prebiotics; (4) nutrient supplements, including zinc, polyunsaturated fatty acids, and amino acids; (5) antiinflammatory agents such as 5-aminosalicyclic acid; and (6) antibiotics in the context of acute malnutrition and infection. Better understanding of the underlying causes of EED and development of noninvasive, practical, simple, and affordable point-of-care diagnostic tools remain key gaps. "Omics" technologies (genomics, epigenomics, transcriptomics, proteomics, and metabolomics) and stable isotope techniques (eg, 13C breath tests) targeted at children and their intestinal microbiota will enhance our ability to successfully identify, manage, and prevent this disorder.

Chylomicron retention disease: A rare cause of chronic diarrhea.

Chylomicron retention disease (CRD) is a rare autosomal recessive hereditary hypocholesterolemic disorder. The disease most frequently presents in infants and is characterized by a lipid malabsorption syndrome with steatorrhea, chronic diarrhea, and growth retardation. The disease is characterized by normal fasting serum triglyceride levels combined with the absence of apolipoprotein (apo) B48 and chylomicrons after a fat load. In this report, we describe the clinical, laboratory, and histological data as well as the molecular DNA analysis of a 12-month-old girl from Tunisia with CRD. The patient was treated with a low-fat diet and fat-soluble vitamin supplementation resulting in significant improvement.

Acquired causes of intestinal malabsorption.

This review focuses on the acquired causes, diagnosis, and treatment of intestinal malabsorption. Intestinal absorption is a complex process that depends on many variables, including the digestion of nutrients within the intestinal lumen, the absorptive surface of the small intestine, the membrane transport systems, and the epithelial absorptive enzymes. Acquired causes of malabsorption are classified by focussing on the three phases of digestion and absorption: 1) luminal/digestive phase, 2) mucosal/absorptive phase, and 3) transport phase. Most acquired diseases affect the luminal/digestive phase. These include short bowel syndrome, extensive small bowel inflammation, motility disorders, and deficiencies of digestive enzymes or bile salts. Diagnosis depends on symptoms, physical examination, and blood and stool tests. There is no gold standard for the diagnosis of malabsorption. Further testing should be based on the specific clinical context and the suspected underlying disease. Therapy is directed at nutritional support by enteral or parenteral feeding and screening for and supplementation of deficiencies in vitamins and minerals. Early enteral feeding is important for intestinal adaptation in short bowel syndrome. Medicinal treatment options for diarrhoea in malabsorption include loperamide, codeine, cholestyramine, or antibiotics.

Clinical relevance of trace element measurement in patients on initiation of parenteral nutrition.

Background and Aims Serum zinc, copper and selenium are measured in patients prior to commencing on parenteral nutrition; however, their interpretation can be difficult due to acute phase reactions. We assessed (i) the relationship of raised C-reactive protein with trace elements and albumin (ii) benefits of measuring trace elements when C-reactive protein is raised in patients requiring short-term parenteral nutrition. Methods Samples were collected for zinc, copper, selenium and albumin at baseline and then every two weeks and correlated with C-reactive protein results in patients on parenteral nutrition. Results were categorized into four groups based on the C-reactive protein concentrations: (i) <20 mg/L, (ii) 20-39 mg/L, (iii) 40-79 mg/L and (iv) ≥80 mg/L. Results In 166 patients, zinc, selenium and albumin correlated (Spearman's) negatively with C-reactive protein; r = -0.26, P < 0.001 (95% CI -0.40 to -0.11), r = -0.44, P < 0.001 (-0.56 to -0.29) and r = -0.22 P = 0.005 (-0.36 to -0.07), respectively. Copper did not correlate with C-reactive protein (r = 0.09, P = 0.25 [-0.07 to 0.25]). Comparison of trace elements between the four groups showed no difference in zinc and copper (both P > 0.05), whereas selenium and albumin were lower in the group with C-reactive protein > 40 mg/L ( P < 0.05). Conclusion In patients on short-term parenteral nutrition, measurement of C-reactive protein is essential when interpreting zinc and selenium but not copper results. Routine measurement of trace elements prior to commencing parenteral nutrition has to be considered on an individual basis in patients with inflammation.

Nutritional status in children with Shwachman-diamond syndrome.

OBJECTIVE: In Shwachman-Diamond syndrome (SDS), pancreatic insufficiency can lead to malabsorption of fat-soluble vitamins and trace elements. The aim of this study was to assess the serum concentrations of vitamins A and E, zinc, copper, and selenium and their deficiencies. METHODS: This retrospective review was performed in 21 children (12 were male; median age, 7.8 years) with genetically confirmed SDS at a tertiary pediatric hospital. Pancreatic enzyme replacement therapy (PERT) and vitamin or trace elements supplements were documented. RESULTS: Twenty patients (95%) had pancreatic insufficiency receiving PERT, 10 (47%) had a combined vitamin and trace element deficiency, 6 (29%) had an isolated vitamin deficiency, and 4 (19%) had an isolated trace element deficiency. Vitamins A and E deficiency occurred in 16 (76%) and 4 (19%) of 21, respectively. Low serum selenium was found in 10 (47%), zinc deficiency in 7 (33%), and copper deficiency in 5 (24%). Eleven patients (52%) were on multivitamin supplementation, and 2 (10%) on zinc and selenium supplements. No statistical differences were found between repeated measurements for all micronutrients. CONCLUSIONS: More than 50% of the children had vitamin A and selenium deficiencies despite adequate supplementation of PERT and supplements. Micronutrients should be routinely measured in SDS patients to prevent significant complications.

[Nutrient Deficiencies after Bariatric Surgery - Systematic Literature Review and Suggestions for Diagnostics and Treatment]. / Nutritive Defizite nach bariatrischer Chirurgie - systematische Literaturanalyse und Empfehlungen für Diagnostik und Substitution.

The increasing prevalence of morbid obesity in Germany is associated with an increasing number of metabolic surgical interventions. Short-term surgical and long-term metabolic complications such as nutrient deficiencies can be considered the main risks of metabolic surgery and its restrictive and malabsorbant surgical procedures. The aim of this compact short overview based on a selective literature search and our own clinical experience is to characterise the long-term metabolic complications, which are specific for the various bariatric procedures, and to refine the published guidelines for supplementation. Restrictive bariatric procedures can be associated with well-known surgical problems such as pouch dilatation or band migration, e.g., after gastric banding. After sleeve gastrectomy, emerging reflux disease can become a substantial problem. The most frequent deficiencies after restrictive procedures are related to B-vitamins whereas iron, folate, vitamin B1 and B12 and vitamin D deficiencies are associated with the malabsorptive procedure such as biliopancreatic diversion, duodenal switch and Roux-en-Y gastric bypass. Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long medical follow-up investigations. The currently available guidelines of German Society of Treatment of Obesity (CAADIP) of DGAV for supplementation should be known and followed, in particular, by the physicians who i) are exceptionally involved in medical care of obese people and ii) do it in full awareness of the obligatory postoperative clinical observation.

For the assessment of intestinal permeability, size matters.

The purpose of this review is to demonstrate that an intestine leaky to small molecules can be impermeable to large antigenic molecules. The author proposes that the permeability of the epithelium to very small sugar molecules such as lactulose/mannitol-used for the past 50 years to gauge intestinal permeability-does not necessarily correlate with epithelial permeability to macromolecules. This article begins with the history and science behind the use of small sugars to measure permeability, a method developed in 1899. The lactulose/mannitol test may give useful information regarding the overall condition of the digestive tract; however, the author suggests that the test is not indicative of the transport of macromolecules such as bacterial toxins and food antigens, which have the capacity to damage the structure of the intestinal barrier and/or challenge the immune system. This article describes the various mechanisms and physiological transport pathways through which increased antigen uptake may result in immunological reactions to food antigens and bacterial lipopolysaccharides, resulting in the pathogenesis of disease. Finally, the article presents evidence indicating that increased intestinal, antigenic permeability plays a key role in the development of various inflammatory and autoimmune disorders. Therefore, more knowledge about the epithelium's permeability to large molecules undoubtedly contributes not only to early detection but also to secondary prevention of many inflammatory autoimmune, neuroimmune, and neurodegenerative disorders.

Hyperammonaemia due to cobalamin malabsorption in a cat with exocrine pancreatic insufficiency.

A 10-year-old domestic shorthair cat showed anorexia, lethargy and ptyalism with hyperammonaemia. Portosystemic shunts were not identified by computed tomography angiography. Biopsy results revealed mild interstinal nephritis and no lesion in the liver. Analysis of urine revealed the presence of a high methylmalonic acid (MMA) concentration. Serum cobalamin (vitamin B(12)) and serum feline trypsin-like immunoreactivity levels were also markedly low. The cat was diagnosed as having exocrine pancreatic insufficiency (EPI). After 5 weeks of parenteral cobalamin supplementation, serum cobalamin concentration had increased and urinary MMA concentration had decreased. This case suggests that hyperammonaemia may be caused by accumulation of MMA due to cobalamin malabsorption secondary to feline EPI.

[Diagnostic and therapeutic procedure for two popular but quite distinct adverse reactions to food - fructose malabsorption and histamine intolerance]. / Diagnostisches und therapeutisches Vorgehenbei zwei populären, aber sehr unterschiedlichen Nahrungsmittelunverträglichkeiten - Fructosemalabsorption und Histaminintoleranz.

Claiming to suffer from adverse food reactions is popular. In contrast to the classical food allergy, there are some pathomechanisms which are evidently dose-dependent. Thus the procedure in diagnosis and therapy must undoubtedly differ from the practice when food allergy is suspected or proven. Nevertheless many patients suffering from dose-dependent adverse reactions to food are given strict elimination diets, which is neither necessary nor helpful and decreases their quality of life broadly. This holds especially true for fructose malabsorption and histamine intolerance. For the latter, the term adverse reaction to ingested histamine is preferred, because histamine intolerance implies that symptoms are caused entirely by an enzyme defect. Why this is not very likely to be the only reason is discussed in this article. Both adverse reactions require an individual approach especially with regard to nutrition therapy. Therefore the task of diagnosis should be to establish an individual profile of tolerated and not tolerated foods taking into account that tolerance can greatly vary by meal composition, frequency and individual triggering factors. In view of this, therapeutic recommendations should not be based on the absolute quantities of the eliciting substance to be eliminated but on a feasible transfer into daily life. Thereby food restriction can be minimized and a high quality of life will be maintained.

Chylomicron retention disease: report of two cases from a Greek Island.

Chylomicron retention disease (CRD), or Anderson disease, is a rare, hereditary cause of fat malabsorption. It is one of the familial hypocholesterolaemia syndromes, along with homozygous hypobetalipoproteinaemia (HBL) and abetalipoproteinaemia (ABL). We report clinical, laboratory and histological data as well as molecular DNA analysis in the case of a 4-month-old boy with failure to thrive and steatorrhea who was diagnosed with CRD. His mother's first cousin, who was diagnosed as hypobetalipoproteinaemia 30 years ago, was also reviewed and his diagnosis was revised to CRD. Both patients were treated with a low fat diet and supplementation with fat-soluble vitamins resulting in significant improvement. In conclusion, CRD is a well-defined cause of fat malabsorption and can be distinguished from other forms of familial hypocholesterolaemia because of its specific lipid profile.

Molecular study of proteinuria in patients treated with B12 supplements: do not forget megaloblastic anemia type 1.

BACKGROUND/AIMS: Current consensus supports the notion that proteinuria is a marker of renal disease with prognostic implications. Whereas most chronic kidney disease patients with proteinuria would often require antiproteinuric agents, there are some exceptions. Megaloblastic anemia type 1 (MGA1) is characterized by megaloblastic anemia due to congenital selective vitamin B(12) malabsorption and proteinuria. In the present study, we describe 2 Israeli Jewish patients with MGA1 and isolated proteinuria. METHODS: Because of their origin, the patients were screened for the presence of the already studied Tunisian AMN mutation, by direct sequencing the corresponding region from genomic DNA. PCR products were purified and sequenced. RESULTS: Genomic DNA sequencing of the AMN gene of both patients confirmed that the acceptor splice site in intron 3 was changed from CAG to CGG (208-2A→G). CONCLUSION: We determined the molecular basis of MGA1 in both patients and discuss the involvement of the cubilin/AMN complex in this pathology and its role in the development of the proteinuria. We also discuss the questionable significance of antiproteinuric treatment for these patients.