A new case of sodium-dependent multivitamin transporter defect occurring as a life-threatening condition responsive to early vitamin supplementation and literature review.

BACKGROUND: Biallelic pathogenic variants in SLC5A6 resulting in sodium-dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin-responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms. METHODS: We describe a case report of a 5-month-old girl presenting two recurrent episodes of metabolic decompensation and massive cardiac failure in the course of an infectious disease. We compare clinical, biological, and genetic findings of this patient to previous literature collected from Pubmed database (keywords: Sodium-dependent multivitamin transporter (SMVT), SMVT defect/disorder/deficiency, SLC5A6 gene/mutation). RESULTS: We highlight the life-threatening presentation of this disease, the stagnation of psychomotor development, the severe and persistent hypogammaglobulinemia, and additionally, the successful clinical response on early vitamin supplementation (biotin 15 mg a day and pantothenic acid 100 mg a day). Metabolic assessment showed a persistent increase of urinary 3-hydroxyisovaleric acid (3-HIA) as previously reported in this disease in literature. CONCLUSION: SMVT deficiency is a vitamin-responsive inborn error of metabolism that can lead to a wide range of symptoms. Increased and isolated excretion of urinary 3-hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life-threatening.

[Respiratory complications of sickle cell anemia in children: the acute chest syndrome]. / Les complications respiratoires de la drépanocytose chez les enfants: le syndrome thoracique aigu.

The acute chest syndrome (ACS) is one of the most frequent complications of sickle cell disease. It affects mostly young children and counts for one quarter of mortality in the young sickle cell disease (SCD) population. This retrospective study evaluates the impact of ACS among hospitalizations for other complications of SCD in patients at the University Childrens' Hospital Reine Fabiola (Brussels, Belgium) in order to isolate clinical conditions associated with a high risk of ACS development. The medical records of all SCD patients aged up to 18 years admitted for all SCD related acute complications over a period of 13 month have been reviewed. Two patient groups have been formed based on the presence of an ACS within the study period. Epidemiologic data, medical history, the clinical presentation at admission but also blood counts in steady state, at admission and along the hospital stay were compared for a total of 96 hospital stays. There is no difference for age or hemoglobin phenotype between the two major patient groups. Male sex and having had a previous ACS episode in the past were significantly more important in the group of patients hospitalized for ACS. Thoracic pain in an SCD patient who doesn't show typical ACS symptoms should be interpreted as a risk factor for ACS. In conclusion, male sex, medical history of at least one ACS and thoracic pain at hospital admission are associated with high risk of developing ACS.

TRIM5 allelic polymorphism in macaque species/populations of different geographic origins: its impact on SIV vaccine studies.

Tripartite motif 5α (TRIM5α) is a potent antiretroviral immune factor present in the cytoplasm of cells of most tissue types. The rhesus macaque TRIM5 gene has been shown to display polymorphism, with different variants being divided into three groups (TRIM5(TFP), TRIM5(Q), and TRIM5(CypA)), which may have divergent retroviral effects on infection. Along with rhesus macaques, cynomolgus macaques are also used in simian immunodeficiency virus (SIV) infection studies. As a consequence, TRIM5 genotyping of these animals will contribute to interpreting the outcome of such studies. The present communication covers Burmese, Chinese, and a large cohort of Indian-origin rhesus macaques, and describes the first large cohort study on TRIM5 polymorphism in outbred cynomolgus macaques. We demonstrate the presence of the TRIM5(TFP) group in cynomolgus macaques. In addition, we have re-evaluated historical samples of rhesus macaques challenged with SIV(mac251), a virus that has been reported to be partially suppressed by particular rhesus macaque TRIM5 variants.

Sickle cell disease from Africa to Belgium, from neonatal screening to clinical management.

AIM: To describe the severity of sickle cell disease (SCD) in newborns in Belgium and evaluate the impact of neonatal screening (NS) on clinical outcome. METHODS: Universal NS of umbilical cord blood for hemoglobinopathy was progressively deployed in Brussels and Liège starting in 1994. No particular population was targeted. Samples were analyzed initially using the isoelectric focusing technique and since 2008 the capillary electrophoresis technique. If a hemoglobin variant was suspected, further analysis was carried out using high performance liquid chromatography. Children presenting major hemoglobinopathy, especially SCD, were referred to a specialized centre for comprehensive management. Preventive measures included antipneumococcal prophylaxis immunization/antibiotic therapy, parental training to recognize severe anemia and splenic sequestration, and transcranial ultrasound recording for early detection of intracranial stenosis. A database was set up in Belgium to collect clinical and laboratory data including parental phenotype, diagnostic technique (neonatal screening or not), major clinical events (episodes of dactylitis, acute chest syndrome, severe anemia, infection, etc), number and duration of required hospitalizations, and treatment used. RESULTS: Screening of 222352 newborns in maternity units in Brussels led to diagnosis of SCD in 145 patients, Adequate data for analysis of clinical outcome was available for 96 of these children born before 2007. Median age in the study group was 4.2 years and the total duration of follow-up was 510 years. Most cases occurred in families from the Democratic Republic of Congo. (64/96 patients; 66.7%) and involved homozygous hemoglobin S disease (80/96 patients; 83.3%). Twenty-seven percent of patients (26/96) presented no severe clinical events during the study (17 SS, median age 2,1 years (0-13.1 years). Conversely 33% presented an episode of dactylitis and 47.9% (46/96) presented recurrent vasoocclusive crises. Severe anemia was observed in 39.6% (38/96) of cases. Six patients (6.3%) developed septicemia despite prophylactic antibiotic therapy and anti-pneumococcal immunization using heptavalent conjugate vaccine and polysaccharide vaccine, No penicillin-resistant strains were observed. The incidence of stroke was 2.1% (3/96). Two patients presenting homozygous hemoglobin S disease died due to septicemia due to non-compliance with antibiotic therapy in one case and severe anemia in one case. All episodes of septicemia and both deaths occurred at the beginning of the NS program. Hydroxyurea therapy was used in 30 patients (31.2%) including 7 in whom transcranial Doppler depicted blood flow abnormalities and 8 in whom allogeneic bone marrow transplantation was performed. CONCLUSIONS: Sickle cell disease is still associated with high morbidity and mortality but clinical care has improved and no death has occurred in the last 10 years. NS is an effective tool for early detection and management of SCD. Neonates with SCD diagnosed by NS in Belgium presented severe manifestations, but clinical outcomes were improved by comprehensive management.

Unusual clinical manifestation of lymphangiomatosis.

A 6-year- old boy presented with disseminated intravascular coagulation and was diagnosed with lymphangiomatosis. Disseminated intravascular coagulation develops in a minority of cases. Bone lesions were present on his left shoulder. The authors discuss the diagnostic findings and medical management.

MIC gene polymorphism and haplotype diversity in rhesus macaques.

Rhesus macaques (Macaca mulatta) mainly originating from India were analysed for their major histocompatibility complex class I-related (MIC) gene repertoire. Thus far, three distinct genes, designated MIC1, MIC2 and MIC3, have been identified in the rhesus macaque. In addition, an MICD pseudogene has been described mapping apart from the other loci in a telomeric direction. Genomic comparisons and the presence of a characteristic microsatellite in exon 5 suggest that the MIC1 gene is the equivalent of the human MICA gene. Hence, the MIC2 gene, lacking the microsatellite - as do humans -, is considered to be the equivalent of human MICB. The MIC3 gene, a hybrid of MICA and MICB, seems to be generated by a crossing-over event with one breakpoint in intron 3 and accordingly is named MICA/B. Apart from their human counterparts, MICA, MICB and MICA/B cluster in separate branches in the phylogenetic tree, confirming the hybrid character of the MICA/B gene. Population analyses have shown that the various genes display polymorphism, and six MICA, five MICB and three MICA/B alleles have been identified. In the panel of homozygous typing cells, two distinct haplotype configurations have been defined by segregation analyses. Each haplotype comprises an MICB gene in conjunction with either an MICA or an MICA/B gene. Furthermore, the presence of a polymorphic microsatellite in the MICA and MICA/B alleles facilitates speedy and accurate haplotyping.

Chronic non-ischaemic congestive heart disease and endomyocardial biopsies. Worth the extra?

The diagnostic yield of endomyocardial biopsies in patients with chronic congestive heart failure of non-ischaemic aetiology remains questionable and, therefore, the use of endomyocardial biopsies under such circumstances is at stake. The present report documents the correlation between the histologic interpretation of endomyocardial biopsies and the corresponding cardiac explants in 13 patients who underwent cardiac transplantation. The biopsy diagnoses in these patients varied from 'compatible with dilated cardiomyopathy' (n = 6) to 'non-conclusive' (n = 4), 'ischaemia' (n = 2) and 'borderline myocarditis' (n = 1). Correlation with the corresponding cardiac explants revealed hypertrophy of myocytes as the leading histologic feature in the majority of cases. Because of the non-specific histopathology of dilated cardiomyopathy, the discrepancy between biopsy diagnoses and the leading explant diagnosis is mostly a matter of semantics. Ischaemia was present at high incidence, but is considered a result of imparied myocardial perfusion rather than the prime mechanism of heart failure. In four cardiac explants myocarditis was encountered, while the corresponding biopsies showed no cellular inflammation. In two, the cellular infiltrates suggested an early state of repair. One heart contained an active and extensive lymphocytic myocarditis. The fourth case showed an eosinophilic myocarditis, most likely acquired after the biopsy was taken. These discrepancies almost certainly relate to the sampling error and the time interval between biopsy and onset of symptoms. The immediate diagnostic yield of the biopsy, in this particular subset of patients, was minimal, particularly with respect to the diagnosis 'myocarditis'. Nevertheless, biopsy diagnoses such as 'compatible with' and 'non-conclusive' do contribute to the final categorization and management of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)