Variant spectrum of PIEZO1 and KCNN4 in Japanese patients with dehydrated hereditary stomatocytosis.

Hereditary stomatocytosis (HSt) is a type of congenital hemolytic anemia caused by abnormally increased cation permeability of erythrocyte membranes. Dehydrated HSt (DHSt) is the most common subtype of HSt and is diagnosed based on clinical and laboratory findings related to erythrocytes. PIEZO1 and KCNN4 have been recognized as causative genes, and many related variants have been reported. We analyzed the genomic background of 23 patients from 20 Japanese families suspected of having DHSt using a target capture sequence and identified pathogenic/likely pathogenic variants of PIEZO1 or KCNN4 in 12 families.

Chronic Nonbacterial Osteomyelitis of the Jaw in a 3-Year-Old Girl.

Differential diagnosis of bacterial osteomyelitis (BOM) and chronic nonbacterial osteomyelitis (CNO) is challenging. Pediatric CNO can be diagnosed at around 10 years of age and when CNO cases involve only the jaw, it is difficult to make a diagnosis in a young child. A 3-year-old female developed CNO at the jaw alone. She presented with no fever, right jaw pain, mild trismus, and a preauricular facial swelling around the right mandible. Computed tomography (CT) revealed a hyperostotic right mandible, with osteolytic and sclerotic changes associated with periosteal reaction. At first, we suspected BOM and antibiotics were administered. Subsequently, CNO was diagnosed, and the patient received flurbiprofen (a nonsteroidal anti-inflammatory drug (NSAIDs)). Lack of a sufficient response led to successful treatment with a combination of oral alendronate and flurbiprofen. Physicians should be aware of CNO, a rare autoinflammatory noninfectious bone disease of unknown etiology, even in young children, although the disease mostly affects older children and adolescents.

Puzzling (IRIDA-Like and Hemolytic) Anemia in a Child With Idiopathic Pulmonary Hemosiderosis.

Before the diagnosis of idiopathic pulmonary hemosiderosis (IPH), unexplained or puzzling anemia may precede and delay in the diagnosis of pediatric IPH is common. A 5.8 years old female child initiated with iron-refractory iron deficiency anemia-like iron deficiency and hemolytic anemia and at 6.8 years of age IPH was materialized, when the patient showed the triad signs of IPH with hemosiderin-laden alveolar macrophages in gastric aspirate. Although time to the diagnosis was previously reported to be ranged from 16 to 30 months, in our case it took 12 months from the initial anemia to IPH diagnosis.

Congenital Hypofibrinogenemia in a Neonate with a Novel Mutation in the FGB Gene.

Detection of severe hypofibrinogenemia (<50 mg/dL) in a neonate soon after birth is alarming because of the risk of hemorrhage. A female neonate was noted to be hypofibrinogenemic (<50 mg/dL) on day 0 of birth; she showed no thrombocytopenia/coagulopathy or hemorrhagic symptoms. Considering the possibility of afibrinogenemia, which may cause bleeding, fresh frozen plasma (FFP) was initiated twice a week to maintain her plasma fibrinogen level at 50-100 mg/dL. Thereafter, we found hypofibrinogenemia in her father and elder sister and plasma fibrinogen levels, determined by clot formation and immunological methods, showed similarly reduced values in both the neonate (proband) and her father. Based on a presumed diagnosis of congenital hypofibrinogenemia, sequencing of the fibrinogen genes was performed, revealing a novel heterozygous mutation of FGB (Genbank NG008833); a p.403Try>Stop. The neonate was treated with repeat FFP infusions until two months of age, when treatment was stopped because she remained asymptomatic.

Difficulty in controlling heavy menstrual bleeding at menarche in a patient with Glanzmann's thrombasthenia.

Glanzmann's thrombasthenia is a rare inherited autosomal recessive bleeding disorder caused by platelet dysfunction. Adolescent girls with Glanzmann's thrombasthenia may experience problematic heavy menstrual bleeding beginning at menarche; this can be difficult to manage. Here, we report the case of an 11-year-old girl with Glanzmann's thrombasthenia who presented with heavy menstrual bleeding at menarche, which was difficult to control. The vaginal bleeding persisted and did not respond to a treatment with packed red blood cells (16 U total), platelet concentrates (70 U total), or administration (>50 doses) of recombinant activated factor VII (rFVIIa). Eventually, a combination of rFVIIa and hormonal therapy (a combined oral contraceptive pill) was introduced. The bleeding stopped at nearly 1 month from onset of menarche. Thereafter, the condition was managed by monthly subcutaneous administration of a GnRH agonist. Management of severe menorrhagia in adolescent patients with Glanzmann's thrombasthenia requires close collaboration with gynecologists or adolescent medicine specialists. More clinical studies are required to identify an effective combination of rFVIIa and hormonal therapy for this condition.

Acute encephalopathy with biphasic seizures and late reduced diffusion associated with Streptococcus sanguinis sepsis.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) develops in association with systemic as well as central nervous system (CNS) viral or bacterial infections. AESD is most often noted with influenza or human herpesvirus 6 infection in previously healthy infants. However, AESD has also been reported in an infant with developmental retardation and in a mentally and motor-disabled adolescent. Here, we report the case of a 4- year-old female with significant development delay due to spinal muscular atrophy, who developed AESD during Streptococcus sanguinis sepsis with no apparent CNS infection. Although the patient had extremely high serum procalcitonin (45.84 ng/mL, reference; <0.4) on admission indicating a poor prognosis, she was successfully managed for sepsis and AESD.

Mild Encephalopathy with Reversible Lesions in the Splenium of Corpus Callosum and Bilateral Cerebral Deep White Matter in Identical Twins.

Identical twin brothers developed mild encephalopathy at the age of 7.0 and 9.7 years (Patient 1) and 10.7 years (Patient 2). Patient 1 had influenza A at the time of his second episode, but triggering agents were not evident at the first episode. The triggering agents in Patient 2 were unclear. The neurological features of both patients included transient facial numbness, left arm paresis, dysarthria, and gait disturbance. Diffusion-weighted images from magnetic resonance imaging showed high signal levels at the splenium of corpus callosum and in the bilateral cerebral deep white matter. These results are characteristic of mild encephalitis/encephalopathy with a reversible isolated splenium of corpus callosum lesion. All three episodes were treated with a methylprednisolone pulse. Acyclovir was also administered to Patient 2 and to Patient 1 during his first episode. Patient 1 received an anti-influenza agent and intravenous immunoglobulin during his second episode. Both patients recovered completely without sequelae. Genetic factors, which may predispose identical twins to develop encephalopathy, are discussed.

Spontaneous Regression of Pulmonary Nodules Presenting as Epstein-Barr Virus-related Atypical Infectious Mononucleosis.

BACKGROUND: Pulmonary nodules associated with Epstein-Barr virus (EBV)-related atypical infectious mononucleosis have rarely been described. OBSERVATIONS: A 12-year-old Japanese boy, upon admission, revealed multiple small round nodules (a total of 7 nodules in 4 to 8 mm size) in the lungs on computed tomography. The hemorrhagic pharyngeal tonsils with hot signals on 18F-fluorodeoxyglucose-positron emission tomography-computed tomography were biopsied revealing the presence of EBV-encoded small nuclear RNA (EBER)-positive cells; however, no lymphoma was noted. The patient was diagnosed as having atypical EBV-infectious mononucleosis associated with primary EBV infection. Pulmonary nodules markedly reduced in numbers and sizes spontaneously over a 2-year period. CONCLUSIONS: Differential diagnosis of pulmonary nodules in childhood should include atypical EBV infection.

Sporadic Epstein syndrome with macrothrombocytopenia, sensorineural hearing loss and renal failure.

We report here a sporadic case of Epstein syndrome, one of the MYH9 disorders. A Japanese boy was first noted to have thrombocytopenia at 3 years of age. Blood smear showed giant platelets but no Döhle-like bodies in the neutrophils. He had no family history of thrombocytopenia, hearing loss, and/or renal failure. Thrombocytopenia took a chronic course and platelet count fluctuated in the range 18 000-46 000/µL, not responding to i.v. immunoglobulin or prednisolone treatment. The patient had episodes of gross nasal bleeding at 7 and 18 years of age. Mild hearing loss was suspected at 6, and proteinuria was first noted at 14 years of age. At the development of renal failure at 24 years of age, he was identified to have de novo R702H MYH9 mutation. This case illustrates the importance of suspecting MYH9 disorder even in cases of chronic macrothrombocytopenia without family history.

Neonatal Sweet's Syndrome Associated with Rectovestibular Fistula with Normal Anus.

Sweet's syndrome, characterized by fever and a painful erythematous rash with a dermal neutrophilic infiltrate, develops primarily due to paraneoplastic phenomena in adults. Sweet's syndrome is very rare in neonates. We report a Japanese female neonate (age <2 months), who developed Sweet's syndrome with episodes of perineal infection in association with congenital rectovestibular fistula with normal anus. Sweet's syndrome was diagnosed basing on clinical features and histopathology of biopsied skin tissues. Rectovestibular fistula was confirmed after the signs of inflammation subsided and the rash disappeared. In the literature, we found another case of neonatal Sweet's syndrome associated with rectovestibular fistula in a Japanese female neonate. The perineal region should be screened for anomalies following diagnosis of Sweet's syndrome in neonates.

Corrigendum to "Gitelman Syndrome in a School Boy Who Presented with Generalized Convulsion and Had a R642H/R642W Mutation in the SLC12A3 Gene".

[This corrects the article DOI: 10.1155/2014/279389.].

Gitelman Syndrome in a School Boy Who Presented with Generalized Convulsion and Had a R642H/R642W Mutation in the SLC12A3 Gene.

An 8-year-old Japanese boy presented with a generalized convulsion. He had hypokalemia (serum K 2.4 mEq/L), hypomagnesemia, and metabolic alkalosis (BE 5.7 mmol/L). In addition, his plasma renin activity was elevated. He was tentatively diagnosed with epilepsy on the basis of the electroencephalogram findings and was treated by potassium L-aspartate and carbamazepine to control the hypokalemia and seizure, respectively. However, a year later, the patient continued to have similar abnormal laboratory data. A presumptive diagnosis of Gitelman syndrome (GS) was then made and the patient's peripheral blood mononuclear cells were subjected to sequence analysis of the SLC12A3 gene, which encodes a thiazide-sensitive sodium-chloride cotransporter. The patient was found to have compound heterozygous mutations, namely, R642H inherited from his father and R642W inherited from his mother. Thus, if a patient shows persistent hypokalemia and metabolic alkalosis, GS must be considered, even if the patient exhibits atypical clinical symptoms.