Primary intestinal lymphangiectasia presenting as limb convulsions: A case report

lNTRODUCTlON

Intestinal lymphangiectasia (IL) is a rare protein-losing enteropathy[1], characterized by small intestinal lymphatic drainage obstruction, chylous ascites, and villi distortion that further cause lymphatic congestion and elevate the lymphatic pressure, thereby resulting in leakage of lymph liquid into the small intestinal lumen. IL can be categorized into two forms, primary IL (PIL) and secondary IL (SIL).PIL, first reported by Milroy in 1892, is more common in children and adolescents, though rarely, it can also occur in adults and has a tendency to occur sporadically with an unknown etiology. Waldmann[2] in 1961 after demonstrating protein loss quantification byCr-labelled albumin revealed that the lymphatic vessels present in the mucosal and submucosal layers of the small intestine were abnormally dilated to varying degrees. Hence, this diagnosis came into existence.

The incidence of PIL is likely to be related to lymphatic dysplasia in infants which is more frequently diagnosed in children (less than 3 years old), but also in adolescents and even elderly cases[3]. Although in most cases lymphatic dilation is typically seen in the descending duodenum, lymphatic dilation in the small intestine is usually mild and segmental, and secondary causes should be excluded. In this case report, a 19-year-old adult man complained of limb convulsions for the past 1 year, which after further investigations, was later identified as PIL. The following medium-chain triglycerides (MCT) nutritional support improved the patient’s condition.

節(jié)水增糧行動(dòng)項(xiàng)目規(guī)?；ㄔO(shè)高效節(jié)水灌溉工程，覆蓋范圍廣、資金投入大，涉及農(nóng)民切身利益，能否長期運(yùn)行發(fā)揮效益關(guān)系經(jīng)濟(jì)發(fā)展和社會(huì)穩(wěn)定，因此項(xiàng)目建設(shè)過程必須要嚴(yán)格管控、建管并重，尤其是項(xiàng)目后期運(yùn)行維護(hù)要嚴(yán)抓不怠。項(xiàng)目實(shí)施過程要加強(qiáng)督查指導(dǎo)，完善管理措施，確保工程質(zhì)量；建成運(yùn)行后要進(jìn)一步完善工程運(yùn)行管護(hù)機(jī)制，落實(shí)運(yùn)行維護(hù)經(jīng)費(fèi)來源，配備專職人員對(duì)地下水水井、輸水管線、微灌設(shè)施和電氣化設(shè)備進(jìn)行定期保養(yǎng)、維護(hù)和更新，保障節(jié)水增糧行動(dòng)工程建設(shè)規(guī)范、使用便捷、管護(hù)得當(dāng)、長期受益。

CASE PRESENTATlON

Chief complaints

A 19-year-old Chinese male patient complained of recurrent limb convulsions for the past 1 year.

History of present illness

The patient experienced recurrent limb convulsions and numbness with an unknown medical history in the absence of any aggravating factors like joint inflammation, edema, headache, dizziness, nausea and vomiting, abdominal distention, pain, or diarrhea, leading to a gradual weight loss by five kilograms,but due to the ignorance of the patient as well as his family, no further treatment was initiated. But 1 wk ago, his symptoms, comprising of limb convulsions and numbness, got so aggravated that he visited the community hospital in April 2021 for a thorough examination that was preceded by laboratory investigations that showed reduced levels of blood calcium 1.50 mmol/L (1.95 mmol/L after correction, normal range: 2.08-2.6 mmol/L), magnesium 0.49 mmol/L (normal range: 0.75-1.02 mmol/L), potassium 3.38 mmol/L (normal range: 3.5-5.5 mmol/L), and albumin 17.27 g/L (normal range: 40-55 g/L) while displaying increased parathyroid hormone (PTH) 113.0 pg/mL (normal range: 15-65 pg/mL). The patient had blood phosphorus at 1.12 mmol/L, TSH at 2.5 mIU/L, and a positive fecal occult blood test(FOBT). He was supplemented with albumin, calcium gluconate injections, and potassium magnesium aspartate. Henceforth, the persistent symptoms like limb convulsions and numbness were relieved after symptomatic treatment for 1 week. He went to the Endocrinology Department of our hospital for a further definite diagnosis.

多年以后，阿飛終于等到了真正自由的時(shí)候——成家立業(yè)。阿飛出生于一個(gè)時(shí)代經(jīng)商的世家，幾代以來雖說不是大富大貴，但從沒做過賠本的生意，到了阿飛這一代已然積攢了不少家業(yè)，家境也算殷實(shí)。在傳統(tǒng)的中國家庭里，一旦有了一點(diǎn)家業(yè)，就會(huì)開始“講究”一些看起來很正式但又是牛頭不對(duì)馬嘴的“傳統(tǒng)風(fēng)俗”，這些“習(xí)俗”一旦講究起來，簡直比要人命還厲害。

History of past illness

The patient consented to his case being published anonymously.

Personal and family history

The patient was born by spontaneous labor at term, was breastfed in infancy, and had normal physical and cognitive development as his peers along with good academic performance. However, he had a history of hemorrhoids but did not have any long-term chronic abdominal pain and diarrhea in adolescence. His parents were healthy while denying any history of familial genetic disease, psychosis,and infection in the older family generations.

Physical examination

The patient’s height was 174 cm, weight was 52 kg, and body mass index was 17.18 kg/m. He did not exhibit widening of either eye distance or base of the nose-bridge and small external ear while his abdomen was flat and soft, with no abdominal tenderness or rebound pain, non-palpable liver and spleen, normal bowel sounds, and limb strength. Especially, no concave edema was found in both lower limbs, whereas the Babinski’s sign, Chvostek's sign, and Trousseau’s sign were negative (Figure 1).

Laboratory examinations

The results of blood biochemistry were: Calcium 2.37 mmol/L (normal range: 2.08-2.6 mmol/L),magnesium 0.73 mmol/L (normal range: 0.75-1.02 mmol/L), potassium 4.19 mmol/L, phosphorus 1.19 mmol/L, parathyroid hormone 16.7 pg/mL (normal range: 15-65 pg/ mL), and albumin 25.2 g/L(normal range: 40-55 g/L). The FOBT was positive (1+).

The results of routine blood tests were: White blood cell count 3.8 x 10/L, lymphocyte count 0.41 x 10/L (normal range: 1.1 x 10/L-3.2 x 10/L), and lymphatic percentage 10.4% (normal range: 20%-50%)

The patient was treated with a low-fat, high-protein, light diet which contains 1800 calorie each day, and with MCT powder supplement, calcium supplement, and vitamin D supplement.

The results of immunological tests were: Immunoglobulin (Ig)A 0.49 g/L (normal range: 0.82-4.53 g/L), IgG 1.44 g/L (normal range: 7.51-15.6 g/L), IgM 0.18 g/L(normal range: 0.46-3.04 g/L),complement (C)30.67 g/L (normal range: 0.79-1.52 g/L), C40.15 g/L (normal range: 0.16-0.38 g/L);transferrin 1.42 g/L (normal range: 2.0-3.6 g/L); copper orchid protein 10.70 mg/dL (normal range: 22-58 mg/dL); B cell count (CD19+) 38 x 10/L (normal range: 50 x 10/L-670 x 10/L), T cell count(CD3+CD45+) 179 x 10/L(normal range: 470 x 10/L-3270 x 106 /L), T helper count (CD3+CD4+) 46 x 10/L (normal range: 200 x 10/L-1820 x 10/L), T inhibitory cell count (CD3+CD8+) 120 x 10/L (normal range: 130 x 10/L-1350 x 10/L); the number of NK cells was normal.

例如，學(xué)習(xí)“研究分泌蛋白依次經(jīng)過的細(xì)胞結(jié)構(gòu)的方法”一節(jié)后進(jìn)行歸納。第二次筆記的內(nèi)容為： 可用“同位素示蹤”來確定某種物質(zhì)在細(xì)胞內(nèi)或生物體內(nèi)的定位。

The patient had normal liver and kidney function, thyroid function, thyroglobulin, thyroglobulin antibody, and thyroid peroxidase antibody. The results of endocrine tests were: ACTH: 8 am 13.2 ng/L,4 pm 12.6 ng/L, 0 am 5.3 ng/L; cortisol: 8 am 174.3 nmol/L, 4 pm 102.7 nmol/L, 0 am ＜ 25 nmol/L;follicle stimulating hormone 5.98 IU/L, luteinizing hormone 7.74 IU/L, estradiol 98.38 pmol/L,testosterone 27.56 nmol/L; insulin-like growth factor-1208 μg/L, and insulin-like growth factor binding protein-34.8 mg/L. Tumor markers, ANA spectrum, ANCA, rheumatoid factor, ESR, and hepatic fibrosis were all in the normal range. Urine immunoglobulin light chain, 24-h urine protein, and 24-h urine calcium within the normal range.

The HIV + RPR panel was Negative, and blood and stool IBD screening showed no obvious abnormalities.

每個(gè)雷達(dá)圖都是由5個(gè)指標(biāo)組成的三角形，且每個(gè)三角形中的一個(gè)角度為已知量，可以通過各指標(biāo)的長度及指標(biāo)間的角度得到每個(gè)三角形的面積，進(jìn)而得到每個(gè)雷達(dá)圖的面積，見公式(1)；同理周長也可以利用三角函數(shù)取得，見公式(2)。

Imaging examinations

B-mode ultrasound imaging of the parathyroid gland revealed a hypo-echoic nodule with a clear boundary and regular shape along with few blood vessels (Figure 2). An MRI examination exhibited no obvious abnormality while an abnormal-signal nodule was found in front of the right middle abdominal psoas muscle, which was considered as an enlarged lymph node followed by a scanty exudate at the abdominal and pelvic cavity, along with cortical soft tissue edema. Capsule endoscopy showed the flat composition of duodenal mucosal villi with no obvious abnormality in the jejunal or ileal mucosa.Gastroscopy exhibited chronic non-atrophic gastritis and duodenal lymphatic dilatation (Figure 3).Subsequent gastric biopsy showed moderate chronic inflammatory cell infiltration distributed around a small mucosal patch in the descending duodenum followed by lymphatic dilatation in the mucosal lamina propria (Figure 4).

FlNAL DlAGNOSlS

Finally, the patient was diagnosed with PIL (Figures 3 and 4).

TREATMENT

The results of fat-soluble vitamin tests were: Vitamin A 0.28 μg/mL (normal range: 0.30-0.70 μg/mL),25-hydroxyvitamin D 5.28 ng/mL (＜ 20 ng/mL suggesting deficiency), vitamin E 4.49 μg/mL (normal range: 0.30-0.70 μg/mL), and vitamin K10.12 ng/mL (normal range: 0.20-2.50 ng/mL).

OUTCOME AND FOLLOW-UP

The patient returned to the clinic 3 mo later, and showed no symptoms of convulsion of the limbs.Meanwhile, blood calcium and albumin in the laboratory examination increased compared with the values before.

顯效:患者的血壓和血脂恢復(fù)正常,心絞痛發(fā)作率減少80%;有效:患者的血壓血脂改善,心絞痛減少50%至80%;無效:患者血壓血脂無改善,心絞痛發(fā)作減少不足50%?？傆行?顯效率+有效率。

DlSCUSSlON

Since the PIL etiology is ambiguous and standardized treatment is inadequate, a study by Alfano[14] revealed that the primary goal of PIL treatment is to reduce protein loss, maintain circulating blood volume, and inhibit excessive tissue fluid production, thereby indicating that pharmacological treatment is the first-line treatment prescribed in the clinic. In the gastrointestinal tract, MCT is decomposed into glycerol and medium-chain fatty acids that are directly absorbed in the portal vein blood flow by small intestinal epithelial cells without going through lymphatic vessels, thus reducing the pressure in lymphatic vessels, lymph leakage, and protein loss. Incorporating an MCT-rich diet in daily life could significantly improve the symptoms and long-term mortality of PIL patients, although it might not improve the inherent lymphatic abnormalities; thus, the patients might need to take the required medications for a longer period of time.

Laboratory tests at presentation suggested hypocalcemia, hypomagneemia, hypoproteinemia, and lymphocytopenia. Further investigation revealed elevated PTH, decreased vitamin D, low immunoglobulinemia, and positive FOBT. First, the patient had hypocalcemia and hypomagnesemia, and the convulsions of the limbs were relieved by treatment with calcium gluconate and potassium magnesium aspartate. Elevated PTH and hypoproteinemia gave us the impression of renal insufficiency, but subsequent negative results of renal function and urinary protein precluded this diagnosis. Laboratory tests revealed normal liver function and negative rheumatoid and tumor markers, so we focused on the parathyroid gland. According to B-ultrasonography, hyperplasia of nodules, elevated PTH, and hypocalcemia were suggested, which first promoted us to consider a disease of endocrinology.

在“導(dǎo)生制”教學(xué)中，學(xué)生的主動(dòng)性、主體性得到了很好體現(xiàn)，但也會(huì)出現(xiàn)一些問題。此時(shí)，教師的主導(dǎo)作用就顯得尤為重要，課前教師必須統(tǒng)籌規(guī)劃，使教學(xué)有條不紊地進(jìn)行。

Considering the possibility of protein-loss enteropathy, subsequent gastroscopy revealed duodenal lymphatic dilation, confirming our assessment. IL could be divided into primary and secondary types.Primary IL is a congenital lesion with an ambiguous incidence rate and disease mechanism though occurring more sporadically despite the involvement of genetic factors in the pathogenesis[5], whereas secondary IL can be caused by several factors as autoimmune diseases (, Crohn’s disease[6],ulcerative colitis[7], and Henoch-Schonlein purpura), tumors (such as non-Hodgkin’s lymphoma[8]),infections (such as rotavirus), portal hypertension, constrictive pericarditis[9], trauma, or surgical injury[10]. In our case report, Crohn’s disease was first excluded as FOBT results showed 1+ repeatedly while blood and stool IBD screening was negative. As the patient had a previous history of hemorrhoids, the anorectal department considered it as hemorrhoid bleeding after the consultation.

2014年11月，遼南地區(qū)首個(gè)醫(yī)療聯(lián)盟——大連醫(yī)科大學(xué)附屬二院醫(yī)療聯(lián)盟(簡稱“聯(lián)盟”)正式成立，成為三級(jí)醫(yī)院牽頭，包括莊河市中心醫(yī)院、普蘭店市中心醫(yī)院、大石橋市中心醫(yī)院等14個(gè)成員單位，貫穿二級(jí)醫(yī)院和基層醫(yī)療機(jī)構(gòu)，橫向覆蓋疑難重癥治療、急診急救、居民健康管理的多維度、三級(jí)聯(lián)動(dòng)區(qū)域醫(yī)聯(lián)體，意在以信息化為支撐，強(qiáng)化聯(lián)盟單位間遠(yuǎn)程會(huì)診和雙向轉(zhuǎn)診、醫(yī)師多點(diǎn)執(zhí)業(yè)和新農(nóng)合實(shí)時(shí)報(bào)銷等功能。

PHP is a genetic disease in which peripheral cells are resistant to PTH[4]. The central link of the disease is PTH resistance, which leads to high blood phosphorus and activation disorders of 25-(OH)D3,eventually leading to hypocalcaemia. Although this disease is common in women but more severe in men, the reported patients showed symptoms at 2 years of age, which became more obvious after the age of 10 but can rarely be seen in people aged 20 years or above. Tetany and intracranial calcification are usually the most common clinical manifestations and imaging features of PHP. PHP patients with vitamin D deficiency have more severe clinical symptoms, and vitamin D deficiency increases the risk of autoimmune disease. Vitamin D is mainly synthesized in the skin of the body, and then converted into 25-(OH)D by the hydroxylation of 25-hydroxylase (CYP27A1) in the liver, which is the main form of vitamin D in the circulation. 25-(OH)D binds to vitamin D binding protein into the blood circulation and generates active metabolite 1,25-(OH)2D under the catalysis of renal 1αhydroxylase (CYP27B1). 1,25-(OH)2D acts on the intestine, kidney, and bone to regulate the metabolism of calcium and phosphorus.In the small intestine, 1,25-(OH)2D promotes the absorption of calcium and phosphorus, and serum 25-(OH)D is inversely proportional to PTH. When the serum 25-(OH)D level decreases, blood calcium decreases and PTH increases. The increased PTH stimulates the activity of 1αhydroxylase and increases the efficiency of 25-(OH)D conversion to 1,25-(OH)2D. In addition, PTH also normalizes blood calcium levels by stimulating osteoclast proliferation, and increasing bone absorption and calcium release. In this case, the patient had low calcium, with a compensatory increase of PTH, and the blood phosphorus level was within the normal range during the onset. The reexamination of PTH returned to normal during the further correction of low calcium, proving that it was a secondary factor, so PHP could be excluded. Parathyroid nodules were also considered nonfunctional.

Some PIL patients are found with abnormal immune system responses in which the decrease of B cells is manifested by the decreasing IgG, IgA, and IgM levels[11]. Some previous studies also reported that PIL patients’ peripheral blood samples contain a very low number of CD4T cells[12] that were significantly lesser than B cells, while the remaining CD4T cells became highly differentiated and sensitized, thereby showing poor proliferation[13]. It was also observed that the patient’s T lymphocytes kept on decreasing in varying degrees in this case. Further evidence will be necessary to determine whether T lymphocytes mediate the immune functions in the intestine, and further lead to the occurrence and development of the disease.

The clinical manifestations of PIL are diverse as they may cause dilatation of the intestinal lymphatic vessels, leading to loss of lymph fluid into the gastrointestinal tract. While it is mainly characterized by edema of varying degrees, it can also manifest as pleural effusion, pericarditis, chylous ascites, diarrhea,fat vitamin deficiency, weight loss, and other symptoms occurring in severe cases. In our case, due to unknown past medical history, diagnosing and providing prompt treatment were initially challenging as there was no clear history of diarrhea and abdominal pain, limb convulsions, or disease symptoms in childhood. The now obvious limb convulsions first appeared when the patient was 18 years of age and manifested themselves as hypocalcemia, hypomagneemia, and hypoproteinemia, along with elevated PTH levels. Due to similar propensity and characteristics, this disease can easily mimic pseudohypoparathyroidism (PHP) and some other similar diseases in internal medicine, which might lead to misdiagnosis and a plethora of unpleasant side effects. Therefore, the foremost thing that is recommended is to reach a definite diagnosis for a positive outcome.

CONCLUSlON

Based on this case, PIL as a potential diagnosis should be considered even in the absence of any adolescent-illness history for adults with recurrent limb convulsions, low calcium and magnesium,hypoproteinemia, and high PTH levels. MCT diet, as a dietary supplement, can effectively improve the clinical symptoms of PIL patients while providing pharmacotherapy after the final diagnosis was made by a thorough detailed analysis.

FOOTNOTES

Cao Y and Feng XH contributed to literature review and manuscript drafting; Cao Y and Ni HX contributed to patient management and data analysis; and all authors approved the final article and assured all the questions regarding the accuracy of the article.

The patient was healthy until the age of 18, with no trauma or any history of tumor.

The authors declare that they have no conflicts of interest to disclose.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Q陳教授，我家寶寶今年3歲，只喜歡古詩古文，對(duì)絕大部分繪本、動(dòng)畫片不感興趣，平時(shí)想通過繪本教他常規(guī)習(xí)慣他都不聽，所以也不會(huì)和小朋友一起玩，只在旁邊看著笑，不參與，參與了就說古詩，不會(huì)說句子或用詞組表達(dá)?，F(xiàn)在上幼兒園了，明顯與班上孩子差距大，我該怎么引導(dǎo)孩子呢？

China

Yun Cao 0000-0002-8788-6312; Xiao-Hong Feng 0000-0002-8991-9384; Hai-Xiang Ni 0000-0002-7005-4851.

信陽師范學(xué)院充分挖掘大別山區(qū)紅色文化，教育引導(dǎo)大學(xué)生傳承革命傳統(tǒng)，傳承紅色基因，大力弘揚(yáng)中華優(yōu)秀傳統(tǒng)文化和革命傳統(tǒng)文化、社會(huì)主義先進(jìn)文化，深化黨史、國史、改革開放史和社會(huì)主義發(fā)展史的學(xué)習(xí)教育。積極探索實(shí)踐育人模式，打通了“講臺(tái)”到“舞臺(tái)”到“平臺(tái)”的通道，不斷夯實(shí)教育效果。信陽師范學(xué)院紅色文化育人的實(shí)踐表明，高校思想政治教育過程中要摒棄簡單生硬的“大水漫灌”，不斷開辟新的路徑，以鮮活的事例感染學(xué)生，以實(shí)踐活動(dòng)使學(xué)生在參與中提升思想水平。高校思想政治教育要不斷提升親和力、覆蓋面和實(shí)效性，積極總結(jié)優(yōu)秀的個(gè)別經(jīng)驗(yàn)，不斷改進(jìn)成為可復(fù)制、高覆蓋的普遍經(jīng)驗(yàn)。

Ma YJ

Wang TQ

Ma YJ