Case Report	Hepatic Veno-Occlusive Disease with Immunodeficiency (VODI): A Case Report and Review of Literature İmmün Yetmezlik ile Birlikte Hepatik Veno-Oklüziv Hastalık (VODI): Bir Vaka Sunumu ve Literatür İncelemesi *İlke YILDIRIM^1 [ID], Işılay TURAN^1[ID], Selami ULAŞ^1[ID], Sezin NAİBOĞLU^1[ID], Gülşah KALAY^1[ID], Çiğdem AYDOĞMUŞ^1[ID] Abstract Hepatic veno occlusive disease with immunodeficiency syndrome (VODI) is an autosomal recessive primary immunodeficiency associated with hepatic vascular occlusion and fibrosis. The immunodeficiency is characterized by severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, and absence of tissue plasma cells. VODI was first described in 1976 in an Australian Lebanese population. In our patient who came to the emergency department with septic shock, all immunoglobulins were too low to count. In the blood analysis of the patient, it was observed that there was no antibody response. Lymphocyte subgroups were almost normal. According to the whole exome sequence (WES) analysis, it was observed that he had a VODI gene defect. There was an increase in intermittent liver function tests and ursodeoxycholic-acid (UDCA) was started. However, hepatic fibrosis has not yet been detected by radiological methods. During the follow-up of our patient, there was serious weight loss due to chronic (prolonged) norovirus infection. The patient is preparing for a bone marrow transplant. The VODI gene defect should be considered in the differential diagnosis in patients with sepsis, invasive infection, and hypogammaglobulinemia, especially in the early stages of life. With early detection of the disease, patients are monitored regularly with intravenous immunoglobulin (IVIG) prophylactic treatments. In this way, patients can be caught before hepatic fibrosis develops and the development of irreversible damage can be prevented, such as failure of the liver. Keywords: Immunodeficiency, Hepatic fibrosis, Sepsis, Cytomegalovirus, Norovirus, Autosomal recessive. Özet İmmün yetmezlik sendromlu hepatik veno oklüziv hastalık (VODI), hepatik vasküler oklüzyon ve fibrozis ile ilişkili otozomal resesif bir primer immün yetmezliktir. İmmün yetmezlik durumu şiddetli hipogamaglobulinemi, kombine T ve B hücre immün yetmezliği, lenf nodlarında germinal merkez yokluğu ve doku plazma hücrelerinin bulunmaması gibi sendromik özellikler ile karakterizedir. VODI ilk kez 1976 yılında Avustralya'daki Lübnanlı bir ailede keşfedildi. Acil servise septik şokla gelen hastamızda tüm immünglobülinler ölçülemeyecek kadar düşüktü. Hastanın kan analizinde antikor yanıtının olmadığı görüldü. Lenfosit alt grupları neredeyse normaldi. Tüm ekzom dizi (whole exome sequence, WES) analizine göre VODI geninde bozukluk olduğu görüldü. Aralıklı karaciğer fonksiyon testlerinde artış oldu ve ursodeoksikolik asit (UDCA) başlandı. Ancak hepatik fibrozis radyolojik yöntemlerle henüz tespit edilmedi. Hastamızın takibinde kronik (uzamış) norovirus enfeksiyonuna bağlı ciddi kilo kaybı mevcuttu. Hastamız kemik iliği nakline hazırlanıyor. Özellikle yaşamın erken evrelerinde invazif enfeksiyonu veya sepsisi olan hastalarda hipogamaglobulinemi tespit edilirse ayırıcı tanıda VODI gen defekti de akla gelmelidir. Hastalığın erken tespiti ile hastalar düzenli olarak ve intravenöz immünoglobulin (IVIG) profilaktik tedavileri ile takip edilmektedir. Bu sayede hastalar hepatik fibrozis gelişmeden yakalanabilir ve karaciğer yetmezliği gibi geri dönüşü olmayan hasarların gelişmesi önlenebilir. Anahtar kelimeler: İmmün yetmezlik, Hepatik fibroz, Sepsis, Sitomegalovirus, Norovirus, Otozomal resesif. Introduction Hepatic veno occlusive disease with immunodeficiency syndrome (VODI) is an autosomal recessive primary immunodeficiency associated with hepatic vascular occlusion and fibrosis. The immunodeficiency is characterized by severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absence of lymph node germinal centers, and absence of tissue plasma cells [1]. It is in the group of combined immunodeficiencies with syndromic features. The expected findings from the disease are hepatic veno-occlusive disease, Pneumocystis jirovecii pneumonia, enteroviral or cytomegalovirus (CMV) infections, predisposition to candida infections, thrombocytopenia, hepatosplenomegaly, and cerebrospinal leukodystrophy [2]. VODI has an estimated frequency of 1:2500 live births in the Lebanese population of Sydney, Australia, with 19 cases identified over a period of 30 years. Including these cases, 25 cases were identified in the literature [1,3]. VODI is associated with an 85% mortality rate if unrecognized and untreated with intravenous immunoglobulin (IVIG) and Pneumocystis jirovecii prophylaxis [1]. Stem cell transplant preparation regimen may not be successful as it can exacerbate hepatic veno-occlusive. Case Report A 45-day-old boy applied to the emergency department with the complaints of fever reaching 40 degrees, respiratory distress, and bruising. There were present exfoliative rash on the body, neck, and face and the heart rate was 220 per minute. The patient was considered to be in septic shock. Fluid deficiency was replaced, meropenem and vancomycin was given to the patient with sepsis dose. The patient was admitted to the ward to be screened for immunodeficiency. Prenatal/natal and family history; he was born prematurely, 33 weeks gestation, 1400 gr. His mother's one kidney is agenesic and she had pre-eclampsia during her pregnancy. Due to prematurity and respiratory distress, he was treated in the neonatal intensive care unit (NICU) for 40 days, 25 of which he was intubated. The patient’s demographic data is indicated in Table 1. The result of the patient’s hemogram and lenfosit subset is mentioned in Table 2. Liver function tests and coagulation parameters were within the reference range. There was no growth in blood and urine cultures. Treatment with fluconazole, acyclovir and trimethoprim-sulfamethoxazole was started at prophylactic dose. The number of copies of CMV-DNA was found to be high, which was routinely checked weekly. The prophylactic acyclovir he was taking was discontinued and ganciclovir was started at 15 mg/kg/day. Although the patient received ganciclovir, the CMV-DNA increased to 180000 IU/ml. 10 doses of IVIG replacement therapy (0.5 gr/kg/dose) every other day were added to the patient's treatment. In the follow-up, CMV-DNA gradually regressed. After seeing two negative CMV-DNA results, the patient's ganciclovir was also discontinued, and acyclovir prophylactic dose was started. The result of the whole exome sequence (WES) panel was seen as a VODI gene homozygous [sp110 c.80dup(p.His28Thrfs*8)] mutation. Our patient's family were not genetically screened. Therefore, the abdomen ultrasonography (USG) and portal venous doppler of the patient was done. Abdomen USG result was that; liver parenchyma echogenicity is heterogeneous, and it may be liver parenchymal disease. Portal Doppler USG result was that; there is a flow pattern showing hepatopetal and respiratory phasicity in the portal system. Portal flow rate is physiological (>11 cm/sec). This USG result is not compatible with veno-occlusive disease. However, our patient will continue to be followed with USG for any veno-occlusive disease that may develop. The patient was consulted to pediatric gastroenterology after both liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values of the patient were observed to increase gradually in the blood tests. The patient was started with ursodeoxycholic acid (UDCA) at 20 mg/kg twice a day. Liver function tests improved, so liver biopsy was not recommended. To read more, see the pdf format of the article ...
DOI: 10.46683/jmvi.2024.87
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^1Department of Pediatric Allergy and Immunology, Başakşehir Çam ve Sakura City Hospital, İstanbul, Türkiye.
*Corresponding author İlke Yıldırım; MD., Department of Pediatric Allergy and Immunology, Başakşehir Çam ve Sakura City Hospital, İstanbul, Türkiye. E-mail: dr.ilkeokte@gmail.com
Received: 08.12.2023 Accepted: 25.12.2023 Published: 02.01.2024
Cite as: Yıldırım İ, Turan I, Ulaş S, Naiboğlu S, Kalay G, Aydoğmuş Ç. Hepatic Veno-Occlusive Disease with Immunodeficiency (VODI): A Case Report and Review of Literature. J Mol Virol Immunol 2024; 5(1): 23-27.
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