Persistent Depression of the Lambda Site with Progressive Skull Deformity May Be a Sign of Suture Closure: Case Series and Pathologic Consideration.

BACKGROUND: Flat head syndrome (FHS) sometimes occurs when a baby maintains the same head position during the first several months of life, causing a skull deformity. FHS usually improves with time and natural growth, although some show aggravation against conservative treatment. We reviewed pathologically proved early closure of skull suture that may be seen secondary to FHS. METHODS: The clinical and radiologic findings of the patients who showed progressive skull deformity resembling FHS were retrospectively reviewed. All the patients underwent surgical treatment and pathologic specimens were obtained. RESULTS: The detected patients included two 5-month-old infants and one 1-year-old child. The former were conservatively treated without any obvious premature suture closure on computed tomography (CT), and later developed progressive tower-like skull deformities. The infants were diagnosed with possible premature fusion of lambda site and underwent removal around lambda depression (LD). The latter showed evident sagittal suture closure on CT with digital markings, and was diagnosed with increased intracranial pressure and underwent cranioplasty of posterior expansion. Histopathologic specimens obtained from the patients' resected sutures showed irregularly narrowed suture structure with ossification and fibrous tissue proliferation within them, supporting the diagnosis of premature closure of the sagittal sutures. Their postoperative courses were uneventful, and their skull deformities subsequently improved. CONCLUSIONS: Conservative therapy-resistant progressive occipital skull deformity with LD may be a sign of early suture closure, even if CT does not show obvious suture closure. The findings are helpful for early diagnosis and might lead to minimal invasive surgery if needed.

Meckel's Diverticulum with Dieulafoy's Lesion: A Cause of Severe Hematochezia.

BACKGROUND: Meckel's diverticulum (MD) is a remnant of the omphalomesenteric duct. Although the majority of MD are asymptomatic, it can present with severe hematochezia. Hematochezia is generally considered to result from a peptic ulcer caused by ectopic gastric mucosa in MD. However, this hypothesis has not been proved. METHODS: 10 cases of surgically resected MD initially presenting with severe hematochezia were histologically examined. RESULTS: Ectopic gastric mucosa was present in 9 cases, two of which also contained ectopic pancreas. No ectopic tissue was found in one case, which shows that bleeding can occur in MD without ectopic gastric mucosa. In addition, a rupture of aberrant submucosal arterioles through the overlying mucosa, a vascular abnormality called Dieulafoy's lesion, was detected in all the 10 cases. CONCLUSION: This study suggests that the actual cause of massive bleeding in MD is not a peptic ulcer, but Dieulafoy's lesion.

A novel PHOX2B gene mutation in an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease.

Congenital central hypoventilation syndrome is a disorder of respiratory control caused by mutations in the paired-like homeobox 2B gene. Mutations in the paired-like homeobox 2B gene are also responsible for Hirschsprung's disease. Variant Hirschsprung's disease is a rarer disorder that does not meet the diagnostic criteria of Hirschsprung's disease, although severe functional bowel obstruction persists. We present a case of an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease. A male infant who was diagnosed to have fetal growth restriction and polyhydramnios was delivered by emergency cesarean section at 30 weeks and 3 days of gestational age due to non-reassuring fetal status. The birth weight was 979 g, and intensive care was started immediately following delivery. The patient exhibited refractory apnea and was diagnosed with congenital central hypoventilation syndrome by genetic testing of the paired-like homeobox 2B gene. The patient also exhibited refractory functional bowel obstruction and was diagnosed to have variant Hirschsprung's disease through pathological examination of his intestinal specimens. The patient grew slowly but surely with intensive care including mechanical ventilation and parenteral nutrition. However, the patient repeatedly suffered from sepsis and died of fungemia at 197 days of age. This is the first congenital central hypoventilation syndrome case that was accompanied with variant Hirschsprung's disease, and the paired-like homeobox 2B mutation detected in this case (NM_003924.3: c.441G > C; p.(Gln147His)) is novel. This case suggests that the paired-like homeobox 2B mutation causes not only congenital central hypoventilation syndrome and Hirschsprung's disease, but also variant Hirschsprung's disease in humans. It also highlights the extreme difficulty in treating premature infants with severe and prolonged functional bowel obstruction.

Diagnosis and Treatment of a Preterm Infant With Inoperable Congenital Hepatoblastoma--A Case Report.

Reports of hepatoblastoma (HB) in preterm infants are quite rare. Herein, we report the clinical management of a preterm infant with inoperable congenital HB. A female fetus that had been diagnosed with a large liver tumor consistent with hemangioma was delivered by emergency cesarean section at 33 weeks of gestation because of fetal distress. Effective antitumor therapy could not be performed, resulting in rapid deterioration and death. The postmortem histopathologic analysis confirmed the tumor as a HB. This report demonstrates the difficulties inherent in both the image diagnosis of HB and in providing efficacious treatments for preterm infants with HB.

Two novel mutations in the lactase gene in a Japanese infant with congenital lactase deficiency.

Intestinal lactase is required for the hydrolysis of lactose that is the most essential carbohydrate in milk and the primary diet source of newborn. Congenital lactase deficiency [CLD (MIM 223000)] is a severe gastrointestinal disorder and is characterized by watery diarrhea due to an extremely low or the lack of lactase activity in the intestinal wall from birth. CLD is a rare disease and occurs more frequently in Finland. Recent studies have shown that mutations in the coding region of the lactase (LCT) gene underlie CLD in patients from Finland and other European countries. Here, we report two novel mutations in the LCT gene in a Japanese female infant with clinical features consistent with those of CLD. She suffered from severe watery diarrhea from the age of 2 days on breast milk/lactose containing cow's milk formula. With the lactose-free hydrolyzed cow's milk formula, diarrhea was stopped, and she has now developed well on a lactose-free diet. She shows a lactose-intolerance pattern on the lactose challenge test. Sequence analysis revealed the two mutations in her LCT gene: c.4419C>G (p.Y1473X) in exon 10 transmitted from her mother and c.5387delA (p.D1796fs) in exon 16 transmitted from her father. Both mutations cause premature truncation of lactase polypeptide and are supposed to be responsible for CLD. To our knowledge, this is the first report on mutations in the LCT gene in Japan. We suggest that an increased awareness is required regarding CLD.

Neonatal lactic acidosis with methylmalonic aciduria due to novel mutations in the SUCLG1 gene.

BACKGROUND: Succinyl-coenzyme A ligase (SUCL) is a mitochondrial enzyme that catalyses the reversible conversion of succinyl-coenzyme A to succinate. SUCL consists of an α subunit, encoded by SUCLG1, and a ß subunit, encoded by either SUCLA2 or SUCLG2. Recently, mutations in SUCLG1 or SUCLA2 have been identified in patients with infantile lactic acidosis showing elevated urinary excretion of methylmalonate, mitochondrial respiratory chain (MRC) deficiency, and mitochondrial DNA depletion. METHODS: Case description of a Japanese female patient who manifested a neonatal-onset lactic acidosis with urinary excretion of methylmalonic acid. Enzymatic analyses (MRC enzyme assay and Western blotting) and direct sequencing analysis of SUCLA2 and SUCLG1 were performed. RESULTS: MRC enzyme assay and Western blotting showed that MRC complex I was deficient. SUCLG1 mutation analysis showed that the patient was a compound heterozygote for disease-causing mutations (p.M14T and p.S200F). CONCLUSION: For patients showing neonatal lactic acidosis and prolonged mild methylmalonic aciduria, MRC activities and mutations of SUCLG1 or SUCLA2 should be screened for.

Focal nodular hyperplasia-like lesion of the liver in a child previously treated for nephroblastoma.

Described herein is the case of an 8-year-old boy who developed a hepatic nodular lesion after having received anti-neoplastic therapy for nephroblastoma. Histological examination of the excised specimen indicated a disordered arrangement of hepatic components with hemangioma-like features. This case was diagnosed as a variant of focal nodular hyperplasia. It is speculated that this hepatic lesion is a late complication of treatment for nephroblastoma and might develop from congenital malformative area of the liver.

Adenomyoma of the stomach mimicking infantile hypertrophic pyloric stenosis.

We report a case of gastric adenomyoma in a 1-month-old girl. This patient presented with gastric outlet obstruction simulating infantile hypertrophic pyloric stenosis. Histologic examination of the excised specimen showed irregularly arranged glands and interlacing smooth muscle bundles surrounding the glandular elements. We suggest that this lesion is not just heterotopia, but hamartoma composed of abnormal mixture of endoderm-derived epithelial component and mesoderm-derived smooth muscle.

Eosinophilic gastroenteritis with cytomegalovirus infection in an immunocompetent child.

A 3-year-old boy developed transient protein-losing gastroenteropathy associated with cytomegalovirus (CMV) infection. Both IgG and IgM antibodies to CMV were positive in a serologic blood test. Upper gastrointestinal endoscopy showed multiple erosions throughout the body of the stomach, without enlarged gastric folds. Histological examination of the biopsy specimens indicated eosinophilic gastroenteritis and CMV infection. The patient had complete resolution without specific therapy for CMV in four weeks. An allergic reaction as well as CMV infection played important roles in the pathogenesis of this case.

PTHrP-independent hypercalcemia with increased proinflammatory cytokines and bone resorption in two children with CD19-negative precursor B acute lymphoblastic leukemia.

Hypercalcemia in childhood acute lymphoblastic leukemia (ALL) is rare and occasionally associated with parathyroid hormone-related protein (PTHrP). However, the pathogenesis of PTHrP-independent hypercalcemia remains unclear. We report two children with precursor B ALL who had marked hypercalcemia (15.8 and 16.6 mg/dl, respectively) and disseminated osteolysis. Serum tumor necrosis factor-alpha (TNF-alpha) and IL-6 were markedly elevated, whereas 1,25(OH)(2) vitamin D(3), intact PTH and PTHrP were decreased or undetected. Analysis of urinary deoxypyridinoline (DPY) or bone biopsy of the osteolytic lesion showed an increased bone resorption, and administration of bisphosphonate improved the hypercalcemia. Patients had ALL with immunophenotype positive for CD10, CD34, and HLA-DR but negative for CD19 and obtained remission with chemotherapy. These findings suggest that increased osteoclastic bone resorption via stimulation with TNF-alpha and IL-6 may be mechanism causing PTHrP-independent hypercalcemia in some patients with precursor B ALL lacking CD19 expression.

Epstein-Barr virus associated Hodgkin lymphoma in a 9-year-old girl receiving long-term methotrexate therapy for juvenile idiopathic arthritis.

We describe a case of Hodgkin lymphoma developing in a 9-year-old girl with polyarticular, rheumatoid factor-positive juvenile idiopathic arthritis treated with methotrexate (MTX), prednisone, and naproxen for 5 years. Pathologic and molecular analyses revealed that the Hodgkin cells contained Epstein-Barr virus and the viral DNA was monoclonal. She achieved complete remission after MTX withdrawal, chemotherapy, and radiation. To the best of my knowledge, this is the sixth report of Hodgkin lymphoma in patients with juvenile idiopathic arthritis receiving low dose MTX therapy.

Delayed separation of the umbilical cord in two siblings with Interleukin-1 receptor-associated kinase 4 deficiency: rapid screening by flow cytometer.

We describe 2 siblings who had interleukin-1 receptor-associated kinase 4 deficiency with a novel mutation in exon 2. They had delayed separation of the umbilical cord. The flow cytometric analysis of monocytic intracellular tumor necrosis factor-alpha production in response to lipopolysaccharide may be a useful method to screen for the disease.