A Novel Ceruloplasmin Mutation Identified in a Chinese Patient and Clinical Spectrum of Aceruloplasminemia Patients

Background and Purpose: Aceruloplasminemia (ACP) is a rare disorder of iron overload resulting from ceruloplasmin (CP) variants. Because of its rarity and heterogeneity, the diagnosis of ACP is often missed or misdiagnosed. Here, we aim to present a clinical spectrum of ACP and raise more attention to the early diagnosis. Methods: Whole exome sequencing (WES) was performed in a Chinese female patient suspected with ACP and her clinical data were collected in detail. The PubMed databases was searched for published ACP patients within the last decade, and we present a systematic review of their clinical features with data extracted from these researches. Results: A novel pathogenic variant (c.2689delC) and a known pathogenic variant (c.606dupA) within ceruloplasmin gene were identified in our patient and confirmed the diagnosis of ACP. Then we reviewed 50 ACP patients including the case we reported here. A possible timeline of symptoms was discovered, anemia appears first (29.7 years old on average), followed by diabetes (37.3 years old) and finally neurological symptoms (52.2 years old). The delay in diagnosis was significantly shortened in patients without neurological symptoms. Biochemical triad including anemia, low to undetectable serum ceruloplasmin, low serum iron and/or hyperferritinemia, showed better sensitivity in diagnosis than clinical triad including diabetes, neurological symptoms and retinal degeneration. Conclusions: Due to the variable symptom spectrum, patients with ACP often visit different departments, which can lead to misdiagnosis. Clinical attention needs to be paid to symptoms and tests that have a warning effect. Prompt diagnosis in the early stage of the disease can be beneficial.

Undetectable serum lithium concentrations after coadministration of liquid lithium citrate and apple juice: A case report

Lithium is a mood-stabilizing medication approved by the FDA for the treatment of acute manic or mixed episodes of bipolar disorder as well as maintenance treatment. Lithium citrate is an oral solution, and the carbonate salt is available as oral capsules or extended-release tablets. A patient with a psychiatric history of PTSD and schizoaffective disorder–bipolar type, maintained on lithium and olanzapine prior to admission, was admitted to an inpatient psychiatric unit due to destabilization, paranoia, and mania. He was started on lithium citrate, administered with apple juice, while admitted due to nonadherence. An initial serum lithium concentration was found to be undetectable. Lithium was then administered with an alternative non–apple juice liquid, at which point serum lithium concentration became detectable and patient clinically improved. Lithium concentrations may be impacted by a number of causes, such as underlying medical conditions, drug interactions, and diet. As the majority of these factors remained stable during the patient's admission and the serum lithium concentration became detectable after switching from apple juice to an alternative non–apple juice liquid, it led to the identification of a possible incompatibility.

PSEUDOHYPOPHOSPHATEMIA IN A PATIENT WITH MULTIPLE MYELOMA

Objective: To discuss the diagnosis and management of paraprotein interference in the setting of multiple myeloma (MM). Methods: We discuss the evaluation of hypophosphatemia in a patient with MM and present a review of the relevant literature. Results: Our patient, who had a history of MM, was found to have persistently undetectable serum phosphate which did not respond to aggressive phosphate replacement. His clinical condition was not consistent with severe phosphate depletion and hence paraprotein interference secondary to MM was suspected. Re-analyzation of samples on a different machine showed normal serum inorganic phosphate levels. Conclusion: Paraprotein interference from MM causing pseudohypophosphatemia can be overlooked and lead to unnecessary treatment. Recognition of this phenomenon is important to all clinicians, especially in light of potential complications of unnecessary treatment.

Efficacy of 24-week Administration of Tenofovir Disoproxil Fumarate in the Management of Naïve Chronic Hepatitis B

BACKGROUND: Chronic hepatitis B (CHB) is becoming a common liver abnormality worldwide. Thus, a series of good management is needed to prevent the progression and complications of hepatitis B infection. Tenofovir disoproxil fumarate (TDF) is one of the drugs of choice that’s used for CHB management. AIM: Limited studies were found regarding the efficacy of tenofovir in dealing with CHB. Hence, the aim of this study is to determine the efficacy of TDF administration for 24 weeks in subjects with naïve CHB in Medan, Indonesia. METHODS: Retrospective study was conducted in Haji Adam Malik Hospital Medan, Indonesia, between January and December 2019. Subjects were CHB patients aged 18 years or older and were treated TDF for 24 weeks. Demographic, clinical, and CHB disease progression parameters (serum alanine aminotransferase [ALT], hepatitis B envelope antigen [HBeAg], and hepatitis B virus deoxyribonucleic acid [HBV DNA]) data were obtained. RESULTS: One hundred and twenty subjects were obtained and divided into 2 groups: HBeAg positive and HBeAg negative. Mean age of subjects was 46.5 ± 10.36 years in HBeAg positive group and 48.6 ± 10.67 years HBeAg negative group, with predominant males’ subjects in both groups (58.3% vs. 61.7%, respectively). Serum ALT normalization and undetectable serum HBV DNA were observed in more than 70% and 65% of subjects in both groups, respectively (both p < 0.001). Serum HBeAg loss was achieved in 10.8% subjects (p < 0.001). No subject showed serum HbsAg loss. CONCLUSION: Our results are consonant with current clinical guidelines and other evidence literature. For both HBeAg-positive and HBeAg-negative populations, TDF administration for 24 weeks has good efficacy in naïve CHB patients.

Novel biomarkers for the management of chronic hepatitis B

Hepatitis B virus (HBV) cannot be eliminated completely from infected hepatocytes because of the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HCC), it is important to manage CHB to prevent HCC development in high-risk patients with high viral replicative activity or advanced fibrosis. Serum biomarkers are noninvasive and valuable for the management of CHB. Hepatitis B core-related antigen (HBcrAg) correlates with serum HBV DNA and intrahepatic cccDNA. In CHB patients with undetectable serum HBV DNA or loss of HBsAg, HBcrAg still can be detected and the decrease in HBcrAg levels is significantly associated with hopeful outcomes. Therefore, HBcrAg can predict HCC occurrence or recurrence. Measurement of the Mac-2 binding protein glycosylation isomer (M2BPGi) has been introduced for the evaluation of liver fibrosis. Because elevated M2BPGi in CHB is related to liver fibrosis and the prediction of HCC development, monitoring its progression is essential. Because alpha fetoprotein (AFP) has insufficient sensitivity and specificity for early-stage HCC, a combination of AFP plus protein induced by vitamin K absence factor II, or AFP plus <i>Lens culinaris</i> agglutinin-reactive fraction of alpha-fetoprotein might improve the diagnosis of HCC development. Additionally, Dickkopf-1 and circulating immunoglobulin G antibodies are the novel markers to diagnose HCC or assess HCC prognosis. This review provides an overview of novel HBV biomarkers used for the management of intrahepatic viral replicative activity, liver fibrosis, and HCC development.

An unusual cause for rib osteomyelitis in the tropics: Cryptococcal osteomyelitis

The more common manifestations of cryptococcal infections are restricted to the central nervous system and lungs. We report an unusual case of fungal osteomyelitis due to Cryptococcus. The patient was a young man who had been adequately treated for pulmonary tuberculosis three years prior. Three months before, he sustained a minor road-traffic accident with only minor abrasions. He presented with subacute chest pain of 15 days’ duration and was found to have radiological evidence of a lytic lesion of the fifth rib. Given prior tuberculosis, he was thought to have a relapse of disease with tuberculous osteomyelitis. Surprisingly, a biopsy revealed evidence of fungal osteomyelitis with Cryptococcus. An evaluation for primary immunodeficiency revealed low CD4 cell counts with undetectable serum IgA and IgM levels. Genetic sequencing proved a genetic mutation consistent with primary T-cell immunodeficiency. The patient responded well to treatment and is asymptomatic on follow-up.

SAT-511 Alpha Gal Allergy in a Hypothyroid Patient

Background: The IgE-mediated allergy to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate expressed on nonprimate mammalian proteins, has gained more clinical significance as it can present with serious, potentially fatal anaphylaxis or angioedema. In general, recognizing a specific allergy is the first step in prescribing avoidance; but with delayed symptoms, uncertain prevalence, and unclear diagnostic approach, alpha-gal allergies are difficult to recognize and prevent. To further complicate the clinical picture, some patients can tolerate small portions of nonprimate mammalian meat or tolerate one kind of meat over another. We hereby present a case that highlights the lack of guidance and resources currently available to treat a patient with alpha-gal allergy and hypothyroidism. Case Presentation: A 45-year-old woman with a history of an alpha-gal allergy and follicular thyroid neoplasm status post right hemithyroidectomy presented with postoperative hypothyroidism. After the surgery, she had undetectable serum thyroglobulin levels; her thyroid stimulating hormone (TSH) levels were ranging 5–6 µIU/mL (not on thyroid replacement). The goal was to prescribe thyroid replacement to initiate cancer suppressive strategy. The American Thyroid Association (ATA) recommends a TSH of 0.5-to-2 mcIU/mL in low risk patients postoperatively. The standard treatment of choice for correcting hypothyroidism is synthetic thyroxine (T4, levothyroxine). Commercially available levothyroxine, liothyronine, combo, and desiccated thyroid formulations - whether brand name, generic, tablet, soft gel capsule, or liquid - all contain meat byproducts and can be a concern for anaphylaxis or angioedema if one has an alpha gal allergy. Because of the possible reactions with all common formulations of thyroid hormone replacement in this patient, choosing a safe option was complicated and involved a multidisciplinary team, including allergy and immunology consultation. Daily parenteral synthetic thyroid hormone therapy was considered; however, it is not practical and was not feasible for the patient. She was eventually prescribed pure Levothyroxine, with a plant-based filler and vegetarian capsule. She tolerated this pure levothyroxine well without any adverse reactions, and the TSH goal was achieved. Conclusion: This case emphasizes the importance of recognizing various risk factors and common drugs associated with the alpha-gal allergy. Further research and pharmaceutical attention to this allergy is needed.