Possible biallelic inheritance in TIE1 in a family with congenital lymphedema, intestinal lymphangiectasia and cutis aplasia.

A short report of two male siblings born with cutis aplasia, lymphedema and intestinal lymphangiectasia, one found to carry bi-allelic variants in the TIE1 gene known to be associated with congenital lymphedema.

Hypomagnesemia in intestinal lymphangiectasia: a case report and review of the literature.

BACKGROUND: Intestinal lymphangiectasia (IL) is a rare disease characterized by dilation of lymphatic vessels and leakage of lymphatic fluids into the intestinal lumen, causing depletion of lymphocytes, protein, lipids, fat-soluble vitamins, and electrolytes. Hypomagnesemia can occur in IL patients but is seldom discussed. CASE PRESENTATION: A 30-year-old Tibetan woman who had chronic diarrhea, edema, tetany, and tingling was diagnosed with IL. Prominent hypomagnesemia was noticed. She was treated with a medium-chain triglyceride (MCT) diet and nutrient supplementation with satisfactory results. We also present a systematic review of hypomagnesemia in IL cases from the published literature. CONCLUSIONS: Hypomagnesemia may be an overlooked complication of IL, thus monitoring serum magnesium concentrations in IL patients is crucial.

Primary intestinal lymphangiectasia: a rare disease as a cause of protein-losing enteropathy.

Primary intestinal lymphangiectasia is a rare disorder associated with protein-losing enteropathy. The main manifestations are those resulting from hypoalbuminemia. Diagnosis requires the typical endoscopic image of intestinal lymphangiectasia and increased 24-hour fecal alpha-1-antitrypsin clearance. Treatment is basically dietary.

A case of primary intestinal lymphangiectasia with non-Hodgkin lymphoma.

BACKGROUND: Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by the loss of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. Increasing evidence has demonstrated an association between PIL and lymphoma. CASE PRESENTATION: A 54-year-old man with a 20-year history of abdominal distension and bilateral lower limb edema was admitted. Laboratory investigations revealed lymphopenia, hypoalbuminemia, decreased triglyceride and cholesterol level. Colonoscopy showed multiple smooth pseudo polyps in the ileocecal valve and terminal ileum and histological examination showed conspicuous dilation of the lymphatic channels in the mucosa and submucosa. A diagnosis of PIL was made. Three years later colonoscopy of the patient showed an intraluminal proliferative mass in the ascending colon and biopsy examination confirmed a malignant non-Hodgkin lymphoma. Then the patient was been underwent chemotherapy, and his clinical condition is satisfactory. CONCLUSION: Our report supports the hypothesis that PIL is associated with lymphoma development.

Primary intestinal lymphangiectasia presenting as limb hemihyperplasia: a case report and literature review.

BACKGROUND: Primary intestinal lymphangiectasia is an exceedingly rare disorder. Epidemiology is unknown. It usually presents with lower extremity swelling, diarrhea, ascites, and protein-losing enteropathy. Since the pathogenesis of edema is usually due to hypoalbuminemia; both extremities are typically involved. The edema can rarely be due to abnormal lymphatic circulation, causing lymphedema, which usually involves both extremities as well. Diagnosis is made by the constellation of clinical, biochemical, endoscopic, and histological findings. Treatment involves dietary modification, to reduce lymphatic dilation in response to dietary fat. Other pharmacologic (e.g., octreotide) and replacement measures may be indicated as well. The most serious long-term complication is intestinal lymphoma. Herein is a case of Primary intestinal lymphangiectasia presenting with unilateral lower limb swelling. CASE PRESENTATION: A 4-year-old boy presents with left foot swelling since the age of 4 months, in addition to intermittent diarrhea, and abdominal swelling. The foot swelling had been evaluated by different health care professionals in the past, and was mislabeled as either cellulitis, or congenital hemihyperplasia. Physical examination revealed mild ascites, and a non-pitting foot edema with a positive Stemmer's sign (lymphedema). Blood work revealed hypoalbuminemia (albumin 2 g/dl), and hypogammaglobulinemia. Endoscopy showed dilated lacteals throughout the duodenum. Histopathologic examination revealed massively dilated lamina propria lymphatics in the duodenal biopsies. The patient was diagnosed with primary intestinal lymphangiectasia. He was treated with high-protein and low-fat diet, and supplemental formula high in medium chain triglycerides. On follow-up, the patient's diarrhea completely resolved, and his ascites and edema improved significantly. CONCLUSIONS: The presence of unilateral lower limb edema should not preclude the diagnosis of systemic disorders, and a high index of suspicion is required in atypical presentations. A good knowledge about Primary intestinal lymphangiectasia manifestations, and physical examination skills to differentiate edema or lymphedema from tissue overgrowth can significantly aid in the diagnosis.

Primary Intestinal Lymphangiectasia: Diagnostic Accuracy of 99mTc-Labeled Human Serum Albumin Nanocolloid SPECT/CT Before Biopsy.

Primary intestinal lymphangiectasia is an unusual cause of protein losing enteropathy due to either congenital malformation or obstruction of lymphatics of intestine. The disease can affect all or only a small part of the small intestine. Peripheral lymphedema may be associated. The diagnosis is based on endoscopic and histopathological findings. A 30-year-old woman presents lower extremity edema with hypoproteinemia, hypoalbuminemia, and hypogammaglobulinemia. Tc-labeled human serum albumin nanocolloid lymphoscintigraphy of the lower extremity demonstrated a dermal backflow in the right extremity consistent with lymphedema and an unusual ileal uptake on SPECT/CT. Diagnosis is confirmed on histopathological evaluation of biopsy of ileum.

Primary intestinal lymphangiectasia diagnosed by video capsule endoscopy in a patient with immunodeficiency presenting with Morganella morganii bacteraemia.

A 24-year-old woman with a medical history of chronic lower extremity oedema, abdominal pain, diarrhoea and recurrent pulmonary infections presented with sepsis from right lower extremity cellulitis. Blood cultures grew Morganella morganii Laboratory evaluation revealed lymphopaenia, hypogammaglobulinaemia, a low CD4+ T-cell count and nutritional deficiencies resulting from protein-losing enteropathy (PLE). CT showed small bowel wall thickening in the jejunum and ileum. Primary intestinal lymphangiectasia (PIL) was the likely diagnosis that explained her PLE and immunodeficiencies. Video capsule endoscopy is an important diagnostic tool for distal small bowel pathology and confirmed patchy areas of lymphangiectasia of the jejunum and ileum. Secondary causes of lymphangiectasia were ruled out. Clinically significant immunodeficiency from PIL has not been frequently documented, and this case adds to the literature of rare infections associated with PIL. Treatment with intravenous antibiotics resolved her septicaemia, while dietary modifications improved her oedema, abdominal pain and diarrhoea.

Biallelic mutation of FBXL7 suggests a novel form of Hennekam syndrome.

Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by congenital lymphedema, intestinal lymphangiectasia, facial dysmorphism, and variable intellectual disability. Known disease genes include CCBE1, FAT4, and ADAMTS3. In a patient with clinically diagnosed Hennekam syndrome but without mutations or copy-number changes in the three known disease genes, we identified a homozygous single-exon deletion affecting FBXL7. Specifically, exon 3, which encodes the F-box domain and several leucine-rich repeats of FBXL7, is eliminated. Our analyses of databases representing >100,000 control individuals failed to identify biallelic loss-of-function variants in FBXL7. Published studies in Drosophila indicate Fbxl7 interacts with Fat, of which human FAT4 is an ortholog, and mutation of either gene yields similar morphological consequences. These data suggest that FBXL7 may be the fourth gene for Hennekam syndrome, acting via a shared pathway with FAT4.

Primary intestinal lymphangiectasia in an adult patient: A case report and review of literature.

BACKGROUND: Primary intestinal lymphangiectasia (PIL), first described in 1961, is a rare disorder of unknown etiology resulting in protein-losing enteropathy. The disease is characterized by dilatation and leakage of intestinal lymph vessels leading to hypoalbuminemia, hypogammaglobulinemia, and lymphopenia. Since the severity and location of lymph vessels being affected can vary considerably, the range of associated symptoms is wide from mild lower-limb edema to generalized edema, abdominal and/or pleural effusion, and recurrent diarrhea, among others. Although usually developing in early childhood, we present the case of a 34-year-old woman with PIL. Moreover, we performed a literature review systematically assessing clinical presentation, and provide a practical approach to facilitate diagnosis and therapy of PIL in adults. CASE SUMMARY: Our patient presented with unspecific symptoms of abdominal discomfort, fatigue, nausea, and recurrent edema of the lower limbs. Interestingly, a striking collinearity of clinical symptoms with female hormone status was evident. Additionally, polyglobulia, hypoalbuminemia, hypogammaglobulinemia, and transient lymphocytopenia were evident. Due to suspicion of a bone marrow disease, an extensive diagnostic investigation was carried out excluding secondary causes of polyglobulinemia and hypoalbuminemia. The diagnosis of primary intestinal lymphangiectasia was established after 22 wk by histological analysis of biopsy samples obtained via enteroscopy. Consecutively, the patient was put on a high-protein and low-fat diet with medium-chain triglycerides supplementation leading to significant improvement of clinical symptoms until 2 years of follow-up. CONCLUSION: PIL can be the reason for cryptogenic hypoalbuminemia, hypogammaglobulinemia, and lymphopenia in adulthood. Due to difficulty in correct diagnosis, treatment initiation is often delayed despite being effective and well-tolerated. This leads to a significant disease burden in affected patients. PIL is increasingly been recognized in adults since the majority of case reports were published within the last 10 years, pointing towards an underestimation of the true prevalence. The association with female hormone status warrants further investigation.

Novel clinical phenotype of generalised lymphatic dysplasia in a neonate: a missed diagnosis.

We report a preterm neonate who had a large cervical cystic hygroma and right chylothorax. She was operated on day-21 and a near-complete resection of cystic hygroma was done. She developed refractory hypoxemia and shock post surgery and died after 24 hours. During autopsy, the chest cavity was found to be filled with chyle. Histopathological examination showed dilated lymphatics in the pleura, hepatic capsule, serosa of stomach and intestines, peri-pancreatic regions, peri-renal capsule and peri-adrenal tissues suggestive of generalised lymphatic dysplasia. Clinical exome sequencing did not reveal any pathogenic mutation in the genes involved in primary lymphatic dysplasia, noonan syndrome or rasopathies.

Hennekam syndrome: an uncommon cause of chylous ascites and intestinal lymphangiectasia in the tropics.

Paediatric chylous ascites in tropics is commonly caused by infections and trauma. We describe the clinical characteristics of an uncommon inherited cause of chylous ascites, Hennekam syndrome, treated by nutritional modification.