Severe demyelination in a patient with a late infantile form of Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is a cholesterol storage disease caused by defective cellular cholesterol transportation. The onset and progression of NPC are variable, and autopsy findings have mainly been reported for the adult and juvenile forms of this disease. Here we report the clinical and pathological findings from a 9-year-old female patient with the late infantile form of NPC due to NPC1 gene mutation. She had notable splenomegaly at 4 months of age. She lost the ability to speak at 18 months of age. She learned to walk, but often fell and could no longer walk after 30 months. At 3 years of age, she was diagnosed with NPC. Sequence analysis of the NPC1 gene revealed compound heterozygous mutation of T2108C (F703S) and C2348G (S813X) (both novel). Thereafter, the patient suffered repeated respiratory infections and died of respiratory failure at 9 years of age. Pathological findings included cerebral atrophy (particularly of white matter), severe demyelination, and the loss of neurons from the cerebrum and from the nuclei of the brain stem. Remnant neuronal cells and microglia in the cerebrum, cerebellum, and brain stem had become swollen and foamy. Neurons of the hippocampal CA1 and Purkinje cells were relatively spared, and senile plaques and axonal spheroids were not present. Foamy cells were also observed in other organs, especially the spleen and bone marrow. The F703S mutation in this patient was localized in a sterol-sensing domain (SSD). Severe neurological phenotypes have been previously reported in patients with missense mutations in an SSD. It is considered that the combination of a nonsense mutation and missense mutation in an SSD was responsible for the severe neurological phenotype of our present patient. While pathological findings of adult/juvenile forms of NPC have included swollen neurons and glia, neuronal cell loss, and NFTs, demyelination may be a predominant finding in the infantile form of NPC.

Hypokalemic rhabdomyolysis in a child with Gitelman's syndrome.

We report here the first published case of a pediatric patient with Gitelman's syndrome (GS) in whom hypokalemia-associated rhabdomyolysis developed. A 13-year-old girl was admitted with weakness of the extremities, walking difficulty and calf pain. Laboratory data showed a serum potassium level of 2.1 mmol/l and a serum creatinine phosphokinase level of 1,248 IU/l plus myoglobinemia. The presence of normomagnesemia was the basis for a genetic analysis of the thiazide-sensitive sodium chloride cotransporter gene, which revealed compound heterozygous mutations in this gene. Prompt fluid expansion and potassium supplementation led to regression of the muscle symptoms. Hypokalemia can be a rare cause of rhabdomyolysis in patients with GS, even in childhood. We emphasize that genetic analysis is advisable to determine whether the suspicion of GS is warranted.

Characteristics of headaches in Japanese elementary and junior high school students: A school-based questionnaire survey.

PURPOSE: Few studies have investigated pediatric headaches in Japan. Thus, we examined the lifetime prevalence and characteristics of headaches among elementary and junior high school students in Japan. METHODS: In this school-based study, children aged 6-15years completed a questionnaire based on the diagnostic criteria of the International Classification of Headache Disorders-3ß to assess headache characteristics and related disability. RESULTS: Of the 3285 respondents, 1623 (49.4%) experienced headaches. Migraine and tension-type headaches (TTH) were reported by 3.5% and 5.4% of elementary school students, respectively, and by 5.0% and 11.2% of junior high school students. Primary headaches increased with age. Compared with TTH sufferers, the dominant triggers in migraine sufferers were hunger (odds ratio=4.7), sunny weather (3.3), and katakori (neck and shoulder pain) (2.5). Compared with TTH, migraine caused higher headache-related frustration (P=0.010) as well as difficulty concentrating (P=0.017). Migraine-related disability was greater among junior high school students (feeling fed up or irritated, P=0.028; difficulty concentrating, P=0.016). TTH-related disability was also greater among junior high school students (feeling fed up or irritated, P=0.035). Approximately half of the students who complained of headache-related disability were not receiving medical treatment. CONCLUSION: This is the first detailed study of headaches in Japanese children to include elementary school students. Nearly 50% of the school children reported headaches and the disruption of daily activities caused by migraine was higher among junior high students than elementary school students.

Human herpesvirus 6 infection mimicking measles: two pediatric cases.

Measles is a highly contagious viral infection associated with clinical symptoms such as fever, cough, conjunctivitis, coryza, eruption and increased serum immunoglobulin M (IgM) antibodies. A clinical diagnosis is easily established when the chain of infection can be followed. However, Japan is currently experiencing sporadic measles outbreaks, which complicate the establishment of diagnosis. Furthermore, other exanthematous infections such as rubella, human parvovirus B19, human herpesvirus 6 (HHV-6) and HHV-7 present with clinical symptoms and IgM antibody levels similar to those in measles. Therefore, real-time polymerase chain reaction virogene testing has been part of Japan's standard diagnostic protocol for measles since 2010. This report presents two pediatric cases clinically resembling measles that were diagnosed as HHV-6 based on a virogene detection test. This underscores the importance of performing pathogen testing to confirm a diagnosis when measles is suspected.

Resolution of cyclic vomiting after appendectomy in a girl.

Cyclic vomiting syndrome is a disorder characterized by recurrent, discrete, stereotypical episodes of nausea and vomiting. Although chronic or recurrent appendicitis may be a cause of recurrent abdominal pain, it rarely meets the diagnostic criteria for cyclic vomiting syndrome. Furthermore, mast cell counts are histologically high in chronic appendicitis. We report a 10-year-old Japanese girl with a cyclic pattern of vomiting that met the stringent diagnostic criteria for cyclic vomiting syndrome, and which was resolved after appendectomy. Histopathologic examination of the resected appendix showed not only acute mucosal inflammation but also chronic inflammatory changes. Because we speculated that recurrent or chronic appendicitis may have been related to the patient's vomiting bouts, we also immunohistochemically investigated the density of mast cells in the specimen. We found that the mast cell density was markedly high in the lamina propria of the appendix. In our patient, a type I hypersensitivity reaction with release of mediators by mast cells could have been the initial factor triggering the recurrent appendicitis, and this stressor could have initiated the vomiting cascade. In conclusion, chronic or recurrent appendicitis could be one of the causes of cyclic vomiting, and must be considered in the differential diagnosis of cyclic vomiting syndrome.

Acute pancreatitis associated with rotavirus infection.

We report the first documented case of pancreatitis associated with rotavirus infection in an infant. Estimation of amylase level is important in infants with severe rotavirus gastroenteritis, hyperamylasemia should alert one to the presence of overt pancreatitis which should be investigated by lipase estimation and/or imaging.