RESUMO
Phosphate has a fundamental role in bone mineralization, and its chronic deficiency has multiple negative consequences in the body including defects in bone mineralization that will manifest in children as rickets and osteomalacia. We present here a young boy known to have Wiedemann-Steiner Syndrome with multiple co-morbidities that necessitated gastric tube feeding. The child at 22 months was found to have hypophosphatemia and a high alkaline phosphatase level associated with rachitic skeletal manifestations that were attributed to low phosphate intake and/or gastrointestinal absorption as there was no evidence of excessive phosphate wasting based on appropriate tubular renal re-absorption of phosphate. The primary nutritional source was an elemental amino acid-based milk formula (Neocate®) from 12 months of age. After switching from Neocate® to another elemental amino-acid based milk formula, all biochemical and radiological abnormalities returned to normal, indicating that the Neocate® formula was the possible cause of the patient's low phosphate intake. However, in the literature, this formula-associated effect was only described in a limited number of patients. Whether or not some patient-related factors, such as the very rare syndrome described in our patient, could influence this effect warrants further exploration.
RESUMO
We report a Saudi girl who presented at birth with neonatal diabetes, duodenal atresia, and progressive cholestasis. After other gene testing was negative, the clinical diagnosis of Mitchell-Riley syndrome was ultimately considered and further genetic analysis revealed a novel missense homozygous variant in RFX6: c.983A>T (p.asp328Val). Despite intensive management, the patient died from severe Klebsiella pneumoniae sepsis at 5 months of age. This rare syndrome should be suspected in any neonate with hyperglycemia complicated by intestinal atresia and/or progressive cholestasis that could suggest biliary hypoplasia. Early recognition and diagnosis through genetic testing are essential for guiding aggressive clinical management as well as family counseling, particularly in light of the high possibility of early death in this highly complex disorder.
RESUMO
Allergy risk has become a significant public health issue with increasing prevalence. Exclusive breastfeeding is recommended for the first six months of life, but this recommendation is poorly adhered to in many parts of the world, including the Middle-East region, putting infants at risk of developing allergic sensitization and disorders. When breastfeeding is not possible or not adequate, a partially hydrolyzed whey formula (pHF-W) has shown proven benefits of preventing allergy, mainly atopic eczema, in children with a genetic risk. Therefore, besides stimulating breastfeeding, early identification of infants at risk for developing atopic disease and replacing commonly used formula based on intact cow milk protein (CMP) with a clinically proven pHF-W formula is of paramount importance for allergy prevention. If the child is affected by cow's milk protein allergy (CMPA), expert guidelines recommend extensively hydrolyzed formula (eHF), or an amino acid formula (AAF) in case of severe symptoms. The Middle-East region has a unique practice of utilizing pHF-W as a step-down between eHF or AAF and intact CMP, which could be of benefit. The region is very heterogeneous with different levels of clinical practice, and as allergic disorders may be seen by healthcare professionals of different specialties with different levels of expertise, there is a great variability in preventive and treatment approaches within the region itself. During a consensus meeting, a new approach was discussed and unanimously approved by all participants, introducing the use of pHF-W in the therapeutic management of CMPA. This novel approach could be of worldwide benefit.
Assuntos
Aminoácidos/administração & dosagem , Alimentação com Mamadeira , Aleitamento Materno , Fórmulas Infantis , Hipersensibilidade a Leite/terapia , Proteínas do Leite/imunologia , Hidrolisados de Proteína/administração & dosagem , Aminoácidos/efeitos adversos , Aminoácidos/imunologia , Alimentação com Mamadeira/efeitos adversos , Consenso , Humanos , Testes Imunológicos , Lactente , Fórmulas Infantis/efeitos adversos , Recém-Nascido , Oriente Médio/epidemiologia , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/epidemiologia , Hipersensibilidade a Leite/imunologia , Proteínas do Leite/efeitos adversos , Hidrolisados de Proteína/efeitos adversos , Hidrolisados de Proteína/imunologia , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Helicobacter pylori (H. pylori) infection is the most common chronic infections. The risk factors for H. pylori infection in both developing and developed countries are closely related to poor living conditions in childhood. This study aimed to establish the prevalence of H. pylori infection and its associated risk factors among children in the western and central regions of Saudi Arabia. METHODS: A prospective cross-sectional study was performed among symptomatic children in National Guard hospitals who underwent esophagogastroduodenoscopy from 2010 to 2013. The gold standard diagnosis of H. pylori infection was histologic presence of the bacteria in the gastric biopsy. The variables analyzed as possible risk factors included demographic and living characteristics, socioeconomic status, potential mode of transmission, and clinical indications of H. pylori infection. RESULTS: A total of 303 children were included in the study. The overall prevalence of H. pylori infection was 49.8%. Among the studied variables, the following were positively associated with the presence of H. pylori in multivariable analyses: age above 10 years(OR = 11.84, 95% CI = 3.90-35.94, p < .0001), an income of <5000 SR (OR = 2.06, 95% CI = 1.07-3.95), more than eight persons in the household (OR = 3.46, 95% CI = 1.67-7.20), bed sharing (OR = 2.26, 95% CI = 1.32-3.86), and two affected parents (OR = 11.19, 95% CI = 1.29-97.27). Abdominal pain and anorexia were significant predictors of H. pylori infection (p = .005 and .009, respectively). CONCLUSION: Helicobacter pylori infection had a high prevalence among Saudi children in the cities of Jeddah and Riyadh. It was a relatively common cause of abdominal pain and anorexia. In this cohort of children, H. pylori infection was associated with variables indicative of a crowded environment and poor living conditions, further supporting the conclusion that improving socioeconomic conditions and designing a preventive health strategy in Saudi Arabia will likely protect children against this infection.
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Infecções por Helicobacter/epidemiologia , Adolescente , Biópsia , Criança , Pré-Escolar , Cidades , Estudos Transversais , Demografia , Endoscopia do Sistema Digestório , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Lactente , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco , Arábia Saudita/epidemiologia , Fatores SocioeconômicosRESUMO
We describe in this report the clinical, biochemical, and molecular features of a Saudi infant with hepatocerebral MDS secondary to a novel homozygous mutation in the MPV17 gene. An automated sequencing of the nuclear MPV17 gene was performed. The coding region (7 exons) of the MPV17 gene was amplified using an M13-tagged intronic primer and screened by direct sequencing of the PCR-amplified products (GenBank Association Number NM_002437.4). The sequencing of the entire coding region and intron-exon boundaries of MPV17 gene revealed a single homozygous variant, -c.278A > C(p.Q93P), which predicts the substitution of a highly conserved amino acid. This particular sequence variant has not been previously reported as a single-nucleotide polymorphism (SNP) or pathogenic mutation. Diagnostic workup for neonatal liver disorders should include mutation screening for known genes. The new advances in molecular genetics can help clinicians establish the diagnosis in a timely fashion, which may prevent a child from undergoing invasive and expensive investigations.
Assuntos
Falência Hepática/genética , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Mutação , Substituição de Aminoácidos/genética , Evolução Fatal , Humanos , Lactente , Hepatopatias/genética , Masculino , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are severe autosomal recessive disorders associated with decreased mtDNA copy number in clinically affected tissues. The hepatocerebral form (mtDNA depletion in liver and brain) has been associated with mutations in the POLG, PEO1 (Twinkle), DGUOK and MPV17 genes, the latter encoding a mitochondrial inner membrane protein of unknown function. The aims of this study were to clarify further the clinical, biochemical, cellular and molecular genetic features associated with MDS due to MPV17 gene mutations. We identified 12 pathogenic mutations in the MPV17 gene, of which 11 are novel, in 17 patients from 12 families. All patients manifested liver disease. Poor feeding, hypoglycaemia, raised serum lactate, hypotonia and faltering growth were common presenting features. mtDNA depletion in liver was demonstrated in all seven cases where liver tissue was available. Mosaic mtDNA depletion was found in primary fibroblasts by PicoGreen staining. These results confirm that MPV17 mutations are an important cause of hepatocerebral mtDNA depletion syndrome, and provide the first demonstration of mosaic mtDNA depletion in human MPV17 mutant fibroblast cultures. We found that a severe clinical phenotype was associated with profound tissue-specific mtDNA depletion in liver, and, in some cases, mosaic mtDNA depletion in fibroblasts.