A case of vitamin B12 deficiency neurological syndrome in a young adult due to late-onset cobalamin C (CblC) deficiency: a diagnostic challenge.

Vitamin B12 deficiency can present with neurologic and psychiatric symptoms without macrocytic anaemia. We describe a case of late-onset cobalamin C deficiency which typically presents with normal serum vitamin B12 concentrations, posing an additional diagnostic challenge. A 23-year-old woman with decreased muscle strength and hallucinations was diagnosed with 'catatonic depression' and admitted to a residential mental health facility. She was referred to our hospital for further investigation 3 months later. Heteroanamnesis revealed that the symptoms had been evolving progressively over several months. Magnetic resonance imaging (MRI) of the brain showed diffuse symmetrical white matter lesions in both hemispheres. Routine laboratory tests including vitamin B12 and folic acid were normal except for a slight normocytic, normochromic anaemia. Over the next 6 weeks her symptoms deteriorated, and she became unresponsive to stimuli. A new MRI scan showed progression of the white matter lesions. The neurologist requested plasma homocysteine (Hcys) which was more than 8 times the upper limit of normal. Further testing revealed increased methylmalonic acid and the patient was diagnosed with adult-onset cobalamin C deficiency. This case illustrates that Hcys and/or methylmalonic acid should be determined in patients presenting with neuropsychiatric symptoms suggestive of vitamin B12 deficiency with a normal serum vitamin B12 to rule out a late-onset cobalamin C deficiency.

An unconscious man with profound drug-induced hypoglycaemia.

INTRODUCTION: Hypoglycaemia has been reported as an unusual complication of tramadol use and in a few cases of tramadol poisoning, but the exact mechanism is not known. CASE DESCRIPTION: An ambulance crew was dispatched to an unconscious 46-year old man. A glucometer point-of-care measurement revealed a profound hypoglycaemia (1.9 mmol/L). Treatment with intravenous glucose was started and the patient was transported to the hospital. The patient had several episodes of pulseless electrical activity requiring cardiopulmonary resuscitation in the ambulance and upon arrival in the hospital. Despite continuous glucose infusion the hypoglycaemia was difficult to correct during the next few hours and the patient developed hypokalaemia. Further investigation to identify the cause of hypoglycaemia revealed that insulin and C-peptide were inappropriately raised. A toxicological investigation revealed the presence of tramadol and its metabolites in lethal concentrations. Also acetaminophen, ibuprofen and lormetazepam were present. Ethanol screening was negative (< 0.1 g/L) and no sulfonylurea were detected. The patient developed multiple organ failure, but eventually recovered. WHAT HAPPENED: The hypoglycaemia was caused by inappropriate stimulation of insulin secretion in a patient intoxicated with tramadol. The sudden hypokalaemia was caused by a massive intracellular shift of potassium in response to the hyperinsulinemia, triggered by the intravenous administration of glucose. MAIN LESSON: To our knowledge, we are the first to document a significant rise in endogenous insulin production in a hypoglycaemic patient presenting with tramadol intoxication. Our observation suggests that hyperinsulinemia could be the cause of the hypoglycaemia associated with tramadol use.

Evaluation of the V8 E-Class, a Novel Automated Capillary Isoelectric Focusing Instrument for Hemoglobinopathy Screening.

OBJECTIVES: We evaluated the performance of a novel capillary isoelectric focusing (CIEF) application for hemoglobinopathy screening on the recently introduced V8 E-Class platform. METHODS: Analytical performance of the V8 E-Class was evaluated and included assessment of hemoglobin A2 (HbA2) imprecision; linearity for HbA2, fetal hemoglobin (HbF), and sickle hemoglobin (HbS); and carryover for HbS. Furthermore, a method comparison with the Minicap Flex Piercing (Sebia, Lisses, France), the Variant Classic (Bio-Rad Laboratories, Hercules, CA), and the G8 (Tosoh Europe, Amsterdam, the Netherlands) was done to assess analytical and clinical concordance. RESULTS: Total HbA2 imprecision was 3.26% and 3.14% for normal and elevated HbA2 controls and 5.16% and 3.58% for a normal and a heterozygous HbS patient sample, respectively. HbA2, HbF, and HbS showed acceptable linearity, and no carryover was observed. The method comparison showed good analytical concordance (r > 0.95) except for a homozygous HbS subset (r = 0.532-0.704). A comparable phenomenon was seen for the clinical concordance with good agreement in samples without variants (weighted κ > 0.80) but poorer agreement in HbS samples (κ < 0.30). CONCLUSIONS: Good analytical performance was demonstrated for this novel CIEF application for hemoglobinopathy screening. Method comparison showed generally good correlation but highlights the need for standardization. Finally, software optimization could further add to its use for routine hemoglobinopathy screening.

Failing blood gas measurement due to methemoglobin forming hemoglobin variants: a case report and review of the literature.

INTRODUCTION: We present a case of an arterial blood gas sample analysis from a 33-year old woman where no oximetry results could be obtained using the Radiometer ABL800 FLEX device. Clinical history of this patient learned that she was carrier of a methemoglobin forming hemoglobin variant type Hyde Park (HbM Hyde Park) and raised the question whether or not this variant could be the cause of the errors obtained during analysis. MATERIALS AND METHODS: A literature search was performed, focusing on methemoglobin forming hemoglobin variants and their influence on oxygenation measurements. An overview of the currently described methemoglobin forming hemoglobin variants is also included. RESULTS AND DISCUSSION: In the presence of dyshemoglobins such as methemoglobin, techniques used to obtain parameters that reflect the patient oxygenation status, such as pulse oximetry and CO-oximetry can be influenced. In these cases, CO-oximetry is the preferred technique because it can compensate for this, in contrast to pulse oximetry. In case of the presence of methemoglobin originating from a hemoglobin variant, it is possible that CO-oximetry data cannot be calculated because the absorbance spectrum of this methemoglobin can differ from regular methemoglobin. Moreover, pulse oximetry devices are actually prone to erroneous results since pulse oximetry data will be calculated in these cases, but unreliable and should be avoided. CONCLUSION: Methemoglobin forming hemoglobin variants are rare genetic mutations. However, they can possibly interfere with the calculation of CO-oximetry values. In these cases, pulse oximetry data should be avoided because they could lead to incorrect medical decisions.

A Mosaic Expression of a Hb J-Amiens (HBB: c.54G > T; p.Lys18Asn) and its Interference with Hb A1c Analysis.

We report the case of a 56-year-old Caucasian woman in whom hemoglobinopathy screening was triggered following an aberrant Hb A1c analysis. Preliminary diagnosis of the hemoglobin (Hb) variant was obtained through cation exchange high performance liquid chromatography (HPLC) and gel electrophoresis. DNA analysis confirmed the presence of Hb J-Amiens [ß17(A14)Lys→Asn; HBB: c.[54G > C or 54G > T)]. However, an unbalanced ratio between wild type and mutant signal after direct sequencing and a lower than expected percentage of this Hb variant led to the suggestion of a mosaic expression. Furthermore, different methods [capillary zone electrophoresis (CZE), cation exchange HPLC and boronate affinity] were tested to study the possible interference of this variant with Hb A1c measurements. These investigations showed a clinically relevant difference between the methods tested. Hb A1c analysis may lead to the discovery of new Hb variants or mosaicism for previously described Hb variants. This may have genetic consequences for the offspring of carriers and brings about the question of partner testing.