|Year : 2014 | Volume
| Issue : 4 | Page : 217-219
Labial minor salivary gland biopsy in neonatal hemochromatosis
Saurabh Kumar1, Binu Govind2, Harshad Parmar3, Santosh Koshy1
1 Department of Dental and Oral Surgery, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
2 Department of Neonatology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
3 Department of General Pathology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
|Date of Web Publication||14-Nov-2014|
Department of Dental and Oral Surgery, OPD Block, Christian Medical College Hospital, Ida Scudder Road, Thottapalayam, Vellore 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Neonatal hemochromatosis, (NH) is a rare congenital disorder of liver associated with a poor prognosis and characterized by extrahepatic siderosis. Often rarely discusses in this disorder is the presence of siderosis in the minor salivary glands of lips. One of the most clinically accessible and consistently involved extrahepatic sites in NH is the labial minor salivary glands. Thus, biopsy of the labial minor salivary glands can help in establishing the diagnosis and initiating early care in such patients. As NH is often diagnosed after the exclusion of other common neonatal causes of liver failure, there is always a delay in diagnosing these patients. Rarely mentioned in the literature, is the role of lip biopsy as an adjunct to the clinical findings for early diagnosis of NH. This paper reports a case of NH for which lip biopsy emphasized on the diagnosis. The histological features seen in NH have also been described.
Keywords: Neonatal hemochromatosis, minor labial salivary gland biopsy, extrahepatic siderosis
|How to cite this article:|
Kumar S, Govind B, Parmar H, Koshy S. Labial minor salivary gland biopsy in neonatal hemochromatosis. J Clin Neonatol 2014;3:217-9
| Introduction|| |
Neonatal hemochromatosis (NH) is characterized by siderosis of the perinatal onset resulting in the deposition of iron in the hepatic and extrahepatic sites.  This rare congenital disorder of the liver is associated to have a poor prognosis and due to lack of effective medical treatment available, liver transplant is often required.  Variable results have been reported with the use of antioxidants and iron chelators, most reports have suggested 10-20% success rate with medical treatment.  The pathogenesis of this acute condition remains unknown, and the most accepted theory is that this condition is an alloimmune disorder causing liver injury in the fetus. In NH sensitized mothers, a transplacental passage of maternal antifetal liver antigen IgG results in the altered iron metabolism that normally passes through the liver, leading to siderosis and NH phenotype. As this condition has an in-utero onset, most patients with NH are stillborn, premature, or small for gestational age, frequently presenting with liver and multiorgan failure at birth.  NH has typically been a diagnosis of exclusion, confirmed only after clinical and laboratory investigations have ruled out other common causes of neonatal liver failure. Often the diagnosis of NH is delayed, therefore, largely affecting the survival of patients with this disease. A liver biopsy specimen showing siderosis is not specific for hemochromatosis and may be risky in patients with coagulopathy.  Demonstration of extrahepatic siderosis will significantly supplement the clinical symptoms in neonates suspected of having this disease. Submucosal labial minor salivary gland biopsy provides an effective method in establishing the diagnosis of NH as it is easy to perform with minimal morbidity. 
| Case report|| |
A female preterm baby was born at 34 weeks of gestation, to a primi mother by lower segment cesarean section in view of non-reassuring fetal status. Antenatal period was complicated by premature prelabour rupture of membranes of 12 h duration. There was no history of any relevant problems in the antenatal period. Ultrasound examination done in the period was normal, and there was no history of polyhydramnios. The parents did not have any family history of liver disease. The baby weighed 1800 g and cried immediately at birth. She was clinically pale though hemoglobin level was normal (Hb 14.4 g%) and had hepatomegaly at birth, so was transferred to the nursery for evaluation. The baby's liver function test showed normal bilirubin (TB 0.8, DB 0.3 mg%); there was low serum albumin (total protein 4.6 g% and albumin 2.8 g%); however, the liver enzymes were grossly elevated (aspartate aminotransferase 2385 U/L; alanine aminotransferase 585 U/L). There was no respiratory distress, and she was not dysmorphic. She was started on nasogastric feeds and was changed to direct breast feeds on day 2 of life. Baby became dusky on day 6 of life, the possibility of sepsis was considered, and treatment was started with antibiotics. Baby developed petechial rash over the body by day 9 of life, and there was associated anemia and thrombocytopenia.
Baby was evaluated repeatedly for sepsis, but blood culture, and C-reactive protein done was always negative. There was gross alteration of prothrombin (37.1 s, INR 3.3), and APTT (>3 min) and multiple plasma transfusions were given in view of the bleeding. Liver function done was suggestive of liver cell failure (serum glutamic oxaloacetic transaminase 3185U/L and serum glutamic pyruvic transaminase 641 U/L) with slightly elevated direct bilirubin suggestive of cholestasis (total bilirubin 4.2; direct bilirubin 3.6). There was associated hypoalbuminemia (2.8 g%). TORCH analysis was done to rule out congenital infection in view of thrombocytopenia and liver involvement, the results of which was nonspecific. Renal function tests were done which was normal. Urine for reducing substances was negative which probably ruled out Galactosemia. The urinary succinylcholine estimation done was negative which ruled out Tyrosinemia. Serum Ammonia level was estimated which was at a higher level probably suggestive of liver dysfunction (282 mcg%). A possibility of primary liver pathology was suspected. Serum iron estimation was elevated (334.3 mcg%); Serum transferrin level was 123.4 mg/dl. In view of the high serum ferritin level (131,533 ng/ml) and alphafetoprotein (15,000 IU/ml), it was decided to evaluate the baby for hemochromatosis. A magnetic resonance imaging (MRI) done was indicative of the diffuse hypodensity in the liver parenchyma. MRI finding of the pancreas also showed hypodensities suggestive of possible iron deposits. Submucosal salivary gland biopsy showed scattered hemosiderophages in the subepithelial stroma [Figure 1]. Special staining with pearl's iron showed hemosiderin pigment within the macrophages thus substantiating the diagnosis of NH [Figure 2]. The general condition of the baby deteriorated by day 11 of life and feeds was stopped in view of the coagulopathy. Antioxidant chelating therapy was not tried as the parents were not willing to escalate the care in view of the poor prognosis and liver transplantation was not advised, as the facility is not available in our hospital. By day 18 of life, she developed pulmonary hemorrhage but parents were not willing to escalate the care in view of the poor prognosis and so she expired on day 18 of life.
|Figure 1: Scattered macrophages in the subepithelial stroma (H and E, ×40 magnification)|
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|Figure 2: Special stain (pearl's iron, ×40 magnification) showing haemosiderin pigment(blue colored) within the macrophages|
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| Discussion|| |
With < 100 cases reported in the English language literature to date from its first description in 1957, NH is described as one of the rare, highly fatal, neonatal iron storage disorder. Due to its rarity, as well as non-specificity in its clinical and laboratory finding, NH is mainly diagnosed based on exclusion, after common neonatal liver disorders are ruled out. Though considered to be severely fatal, patients can still be stabilized in some cases and prepared for definitive treatment in the form of liver transplantation.  Even early pharmacological management has been shown to reduce the high mortality rate associated with this disease. Clinical signs of liver failure and laboratory finding such as hyperferritinemia, hypersideremia, and hypersaturation of iron binding capacity are often characteristic but not diagnostic for NH. Thus, search for accurate diagnostic entity for this rare acutely fatal condition has always been a challenge. Labial salivary gland biopsy is a simple and effective adjunct in diagnosing NH. Though hemosiderosis is also seen in other neonatal liver failure such as Rubella, alpha-thalassemia, tyorosenemia, renal, hepatic, pancreatic cystic dysplasia, these conditions have distinctive clinical and laboratory findings to infer subsequent diagnosis. Sporadic studies seen in the literature done by Smith et al., Udell et al. have all supported the labial minor salivary gland biopsy by showing it to be highly sensitive and specific in NH patients with typical clinical and laboratory findings. ,
As often seen these patients have severe liver damage with deranged coagulation parameter and are too ill to tolerate traditional liver biopsy. Minor salivary gland biopsy can be easily performed under local anesthesia from easily accessible site of lower lip submucosa [Figure 3]. Not only the procedure is fast but also is minimally traumatic to obtain adequate tissue for biopsy. The only drawback associated with labial minor gland biopsy is that the amount of hemosiderin in the acinar epithelial cells of minor salivary glands is minimal and often related to disease progression thus getting false negative results in early stage disease as noted by Smith et al.  However, labial gland biopsy stands out due to the simplicity of procedure and minimal associated morbidity, although a case series is needed to see the significance of labial mucosal biopsy in diagnosing this rare entity.
|Figure 3: Lower labial biopsy site with vicryl sutures in place showing complete haemostasis|
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| Conclusion|| |
In need for initiating early medical intervention in NH in order to get improved outcome in these patients, labial minor gland biopsy for submucosal acinar hemosiderin deposits helps in supplementing the diagnosis of this severely fatal condition.
| References|| |
|1.||Smith SR, Shneider BL, Magid M, Martin G, Rothschild M. Minor salivary gland biopsy in neonatal hemochromatosis. Arch Otolaryngol Head Neck Surg 2004;130:760-3. |
|2.||Timpani G, Foti F, Nicolò A, Nicotina PA, Nicastro E, Iorio R. Is exchange transfusion a possible treatment for neonatal hemochromatosis? J Hepatol 2007;47:732-5. |
|3.||Rodrigues F, Kallas M, Nash R, Cheeseman P, D'Antiga L, Rela M, et al. Neonatal hemochromatosis - Medical treatment vs. transplantation: The king's experience. Liver Transpl 2005;11:1417-24. |
|4.||Whitington PF. Fetal and infantile hemochromatosis. Hepatology 2006;43:654-60. |
|5.||Chan KC, Edelman M, Fantasia JE. Labial salivary gland involvement in neonatal hemochromatosis: A report of 2 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:e27-30. |
|6.||Grabhorn E, Richter A, Burdelski M, Rogiers X, Ganschow R. Neonatal hemochromatosis: Long-term experience with favorable outcome. Pediatrics 2006;118:2060-5. |
|7.||Udell IW, Barshes NR, Voloyiannis T, Lee TC, Karpen SJ, Carter BA, et al. Neonatal hemochromatosis: Radiographical and histological signs. Liver Transpl 2005;11:998-1000. |
[Figure 1], [Figure 2], [Figure 3]