Yasuji Inamo

Compound Heterozygous Mutations in SLC30A2/ZnT2 Results in Low Milk Zinc Concentrations: A Novel Mechanism for Zinc Deficiency in a Breast-Fed Infant

Zinc concentrations in breast milk are considerably higher than those of the maternal serum, to meet the infants requirements for normal growth and development. Thus, effective mechanisms ensuring secretion of large amounts of zinc into the milk operate in mammary epithelial cells during lactation. ZnT2 was recently found to play an essential role in the secretion of zinc into milk. Heterozygous mutations of human ZnT2 (hZnT2), including H54R and G87R, in mothers result in low (>75% reduction) secretion of zinc into the breast milk, and infants fed on the milk develop transient neonatal zinc deficiency. We identified two novel missense mutations in the SLC30A2/ZnT2 gene in a Japanese mother with low milk zinc concentrations (>90% reduction) whose infant developed severe zinc deficiency; a T to C transition (c.454T>C) at exon 4, which substitutes a tryptophan residue with an arginine residue (W152R), and a C to T transition (c.887C>T) at exon 7, which substitutes a serine residue with a leucine residue (S296L). Biochemical characterization using zinc-sensitive DT40 cells indicated that the W152R mutation abolished the abilities to transport zinc and to form a dimer complex, indicating a loss-of-function mutation. The S296L mutation retained both abilities but was extremely destabilized. The two mutations were found on different alleles, indicating that the genotype of the mother with low milk zinc was compound heterozygous. These results show novel compound heterozygous mutations in the SLC30A2/ZnT2 gene causing zinc deficiency in a breast-fed infant.

Anakinra therapy for CINCA syndrome with a novel mutation in exon 4 of the CIAS1 gene.

UNLABELLED We report on a patient with chronic infantile neurological cutaneous and articular (CINCA) syndrome. Sequence analysis revealed a novel missense mutation in exon 4 of the CIAS1 gene. The patient was unresponsive to several treatments including prednisolone, immunosuppressants (azathioprine and cyclosporin), disease-modifying antirheumatic drugs (DMARDs: penicillamine, salazopyrin and methotrexate) and the tumour necrosis factor-alpha (TNF-a)-blocker infliximab. At 32 mo of age, administration of the recombinant human interleukin-1 receptor antagonist anakinra commenced, which caused an immediate and marked improvement in the clinical symptoms and laboratory test results. Continuous inhibition of the inflammation required a dose of 1.0 mg/kg every 12 h. CONCLUSION Following the diagnosis of CINCA syndrome, anakinra treatment should be commenced as the first line of therapy.

Serum vitamin D concentrations and associated severity of acute lower respiratory tract infections in Japanese hospitalized children

Background:  Vitamin D is an immunomodulatory molecule related to innate immunity that may contribute to the increased occurrence of acute lower respiratory infection (ALRI) in children, one of the most common reasons for hospitalization and intensive care unit admission. In the present study, the association between vitamin D deficiency and the severity of respiratory infection was evaluated by determining serum concentrations of 25‐hydroxyvitamin D (25(OH)D) in a group of hospitalized children with ALRI.

Posterior reversible encephalopathy syndrome in childhood: report of four cases and review of the literature.

Background Posterior reversible encephalopathy syndrome (PRES) is a recently described disorder with typical radiological findings of bilateral gray and white matter abnormalities in the posterior regions of the cerebral hemispheres and cerebellum. Its clinical symptoms include headache, decreased alertness, mental abnormalities such as confusion, diminished spontaneity of speech, and changed behavior ranging from drowsiness to stupor, seizures, vomiting, and abnormalities of visual perception such as cortical blindness. In this study, the clinical and radiological findings of 4 children with this syndrome due to a variety of conditions are reported. Methods The records of 4 children with a diagnosis of PRES were retrospectively analyzed. Results PRES is associated with a disorder of cerebrovascular autoregulation of multiple etiologies. Four patients with PRES who had primary diagnoses of severe aplastic anemia, nephritic syndrome, Henoch-Schönlein purpura, and acute poststreptococcal glomerulonephritis are presented. This syndrome has been described in numerous medical conditions, including hypertensive encephalopathy, eclampsia, and with the use of immunosuppressive drugs. Conclusions Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate precise diagnosis and appropriate treatment.

Spontaneous pneumomediastinum complicating pneumonia in children infected with the 2009 pandemic influenza A (H1N1) virus

We report two occurrences of spontaneous pneumomediastinum (SPM) complicating pneumonia in Japanese children infected with the novel influenza A (H1N1) virus (IV). General practitioners especially should suspect possible SPM when examining and treating children with the novel influenza accompanied by status asthmaticus or wheezing. The presented patients illustrate the specific clinical and radiological signs associated with SPM complicating pneumonia in children infected with A(H1N1)v.

Intravenous Ulinastatin Therapy for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Pediatric Patients

Background: More effective therapy is needed for the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The clinical efficacy of intravenous ulinastatin therapy was investigated in 3 Japanese pediatric patients with SJS or TEN. Methods: Ulinastatin was given to 1 pediatric SJS patient and 2 pediatric TEN patients within 7 days (patient 1; SJS), 6 days (patient 2; TEN), or 4 days (patient 3; TEN) after the onset of the skin rash. Ulinastatin was administered intravenously at a dose of 7,500 U/kg/day (maximum dose: 300,000 U/day). No corticosteroids were given. After the skin lesions resolved, the ulinastatin dose was reduced to between 2,500 and 5,000 U/kg/day as maintenance therapy and then the drug was withdrawn. Results: Erythema, fatigue, and fever improved within 12–36 h of starting the ulinastatin infusion, and the skin lesions resolved completely after 4–7 days of ulinastatin therapy. None of the patients had cutaneous or ocular sequelae. No patient developed secondary infection or relapse and ulinastatin therapy caused no side effects. Conclusion: Ulinastatin dramatically reduced the febrile period with no adverse effects and was very safe in this study. Ulinastatin appears to be a useful and effective therapy for controlling SJS and TEN without sequelae.

A 4-year-old girl with clinically mild encephalopathy with a reversible splenial lesion associated with rotavirus infection

Rotavirus is a common cause of severe gastroenteritis in children. It is known that rotavirus gastroenteritis may be accompanied by neurological manifestations, including encephalitis/encephalopathy and seizures. We report a case of a 4-year-old girl with clinically mild encephalopathy with a reversible splenial lesion associated with rotavirus infection. She was admitted to our hospital because of reduced level of consciousness, seizures, diarrhea, and vomiting. Fecal rotavirus antigen testing was positive. Cell counts in the cerebrospinal fluid (CSF) were normal. She had a normal serum sodium level on admission. Brain computed tomography showed no cerebral edema. However, electroencephalography showed generalized high-voltage slow waves, and diffusion-weighted magnetic resonance imaging demonstrated a transient abnormality in the splenium of the corpus callosum. We diagnosed clinically mild encephalopathy with a reversible splenial lesion associated with rotavirus infection. She recovered well and exhibited no neurological sequelae. Rotavirus RNA and antigen were not detected in the CSF, suggesting that the reversible splenial change was caused by indirect effects on the central nervous system subsequent to viral infection. Her normal serum sodium level indicates that this change can occur without hyponatremia.

Agenesis of the internal carotid artery and congenital pituitary hypoplasia: proposal of a cause of congenital hypopituitarism

We describe a patient with microphallus without pigmentation and multiple pituitary hormone deficiencies. The left internal carotid artery and carotid canal were absent and the pituitary gland and sella turcica showed hypoplasia on MRI and magnetic resonance angiography. The internal carotid artery develops in the 4th embryonic week, while the pituitary primordium develops in the 3rd to 4th week. This suggests a possible relationship between internal carotid artery and congenital hypopituitarism. However, there is bilateral blood supply to the hypophysis via the superior and inferior hypophysial arteries, so it is unknown why pituitary hypoplasia may arise from blocking the unilateral blood supply. Conclusion:disruption of internal carotid artery perfusion may lead to pituitary hypoplasia with congenital hypopituitarism as a new disease entity in humans.

The relationship between drug treatment and the clinical characteristics of febrile seizures

BackgroundDrugs such as theophylline, antihistamines, and antiallergics with anti-histaminic actions have been shown to induce febrile seizures. The relationship between febrile seizures and medications has not been actively investigated. The present study aimed to investigate the relationship between the clinical characteristics of febrile seizures and the use of medications.MethodsTwo hundred and sixty-five children treated at our emergency room due to febrile seizures were studied to investigate the relationship between the clinical characteristics of febrile seizures, such as the type and duration of convulsions, and the drug treatment.ResultsThe duration of convulsions was longer among children who took theophylline and antihistamines than among children who did not take these medications. Of the antihistamines, mequitazine did not prolong the duration of convulsion.ConclusionsTheophylline should not be used in febrile children, particularly infants. Cautions should be taken in using histamine H1 antagonists in young infants because such drugs could potentially disturb the anticonvulsive central histaminergic system. However, mequitazine appears to be a suitable antihistamine for use in children with febrile seizures, since it does not prolong convulsions.

Findings on magnetic resonance imaging of the spine and femur in a case of McCune-Albright syndrome.

Polyostotic fibrous dysplasia, a major osseous change in McCune-Albright syndrome, is seen in the cranium, facial bones, bones of the extremities, and ribs, but rarely in the spine. Spinal X-rays revealed no abnormalities in an 8-year-old girl with this syndrome, but99mTc-methylene diphosphonate bone scintigraphy disclosed high-density areas in the thoracic and lumbar vertebrae. Multiple well-circumscribed areas of low signal intensity were seen on T1-weighted magnetic resonance imaging (MRI) of the spine. Although MRI spine scans in this disease have never been reported, our findings in this case proved interesting for evaluating osseous lesions. MRI made it possible to differentiate between fibrous lesions (low signal intensity on T1- and T2-weighted MRI) and cartilaginous lesions (low signal intensity on T1-weighted MRI and high signal intensity on T2-weighted MRI).