A pediatric case of autosomal dominant hypocalcemia type 2.

OBJECTIVES: Autosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia and hyperphosphatemia secondary to hypoparathyroidism. It is classified as type 1, caused by gain-of-function mutations of the calcium-sensing receptor (CASR), and type 2, caused by activating mutations in GNA11, which is a crucial mediator of CASR signaling. What is new? We report a rare pediatric case of ADH type 2. CASE PRESENTATION: The patient was a 15-year-old girl with short stature. Blood tests demonstrated hypocalcemia and hyperphosphatemia without elevated parathyroid hormone levels. Brain computed tomography revealed calcification in the bilateral basal ganglia. Genetic testing revealed the rare GNA11 mutation, c.1023C>G (p.Phe341Leu). The patient was diagnosed with ADH type 2. She had experienced numbness and tetany in her hands for several years, which improved with alfacalcidol therapy. CONCLUSIONS: Our patient is the third female and first pediatric reported case of a variant mutation in the GNA11 gene (ADH type 2), c.1023C>G (p.Phe341Leu).

Central Precocious Puberty (CPP) in Two Girls With Autism Spectrum Disorder (ASD).

In recent years, some cases of central precocious puberty (CPP) have been reported in patients with autism spectrum disorder (ASD). Here, we report CPP in two girls with ASD. The first case was a girl, 7 years and 9 months of age. Breast budding was observed at 7 years and 2 months and pubic hair at 7 years and 8 months of age. She was diagnosed with CPP based on guidelines and ASD according to her developmental history. Considering the psychosocial burden caused by the discrepancy between her cognitive and behavioral development and the progression of secondary sex characteristics, gonadotropin-releasing hormone (GnRH) analog therapy was initiated. Case 2 was a girl, 9 years and 8 months of age. She was diagnosed with ASD according to her developmental history. Treatment using oral aripiprazole for hypersensitivity to touch and taste had been initiated, with the onset of menarche at 9 years and 10 months of age. Breast budding had been observed before 7 years and 6 months old. She was diagnosed with CPP based on guidelines. Considering that menarche was not a significant psychosocial burden and the difficulty for her and her family to attend regular follow-ups, GnRH analog therapy was not initiated. Although the pathophysiological pathway linking ASD and CPP remains to be elucidated clinically, attention to CPP in ASD is needed, considering the increase in reported cases. In addition, the indication of GnRH analog therapy should be judged considering the psychosocial burden associated with secondary sexual characteristics.

A Pediatric Case of Autism Spectrum Disorder With a Prostatic Abscess.

There are few reports of prostatic and periprostatic abscesses in children, and diagnosis is often difficult due to the lack of early symptoms. In addition, children with autism spectrum disorder may have difficulty reporting symptoms, with and without cognitive impairments. This article reports the case of a five-year-old boy with autism spectrum disorder and multiple prostatic abscesses caused by Pseudomonas aeruginosa. He also had various vitamin and mineral deficiencies, presumably related to an unbalanced diet. The patient was treated with antibiotics, vitamins, and trace elements. After his blood vitamin and trace element levels returned to normal, he experienced no fever or relapse. The cause of this prostatic abscess was suggested to involve vitamin and trace element deficiencies.

An Infant With Congenital Tracheal and Bronchial Stenosis Diagnosed by Chest Three-Dimensional Computed Tomography.

In this case report, we describe the case of an infant with repeated wheezing diagnosed relatively early with congenital tracheal and bronchial stenosis after evaluation by chest three-dimensional computed tomography (3D-CT). The patient was a six-month-old male infant with a one-month history of cough and wheezing. His symptoms worsened the day before admission, and he was admitted with pneumonia and wheezing. However, wheezing continued after treatment with intravenous steroids and inhalation of a short-acting ß2-stimulant. 3D-CT of the chest revealed tracheal stenosis, right bronchial stenosis, and right tracheobronchial bronchus. The patient was finally diagnosed with congenital tracheal and bronchial stenosis via bronchoscopy. A virtual bronchoscopic navigation image of the tracheal lumen was created based on the CT images. Although virtual bronchoscopic navigation is more difficult for the dynamic evaluation and evaluation of mucosal lesions than bronchoscopy, it has the advantage of not directly invading the airway. Therefore, if a fixed stenotic lesion is suspected at a facility where bronchoscopy is difficult, evaluation using chest 3D-CT and virtual bronchoscopic navigation may be helpful for diagnosis. In conclusion, congenital tracheal/bronchial stenosis should be considered in patients with prolonged wheezing and recurrent airway infections, and evaluation by chest 3D-CT and virtual bronchoscopic navigation may be helpful for diagnosis.

Obturator pyomyositis and labium majus cellulitis: A case report and literature review.

Pyomyositis is a rare, subacute, deep bacterial infection of the skeletal muscle. When treatment is delayed, pyomyositis causes abscess formation and progresses to sepsis; therefore, its early diagnosis is important. However, the clinical presentation and laboratory findings of pyomyositis are not specific; hence, diagnosis often takes time. We encountered the case of a girl with obturator pyomyositis and redness and swelling of the labium majus, which we considered as potentially important symptoms for distinguishing obturator pyomyositis from septic hip arthritis. An 8-year-old Japanese girl presented to our hospital with fever and right hip pain. On physical examination, she had redness and swelling of the right labium majus and a right limp. She was diagnosed with obturator pyomyositis and labium majus cellulitis with magnetic resonance imaging. Her clinical presentation markedly improved after starting antibiotic therapy with intravenous cefazolin for 2 weeks and oral cefaclor for 1 week. Improvement in the inflammation of the obturator muscle and labium majus was confirmed with follow-up magnetic resonance imaging. She recovered fully with no long-term sequelae. In conclusion, obturator pyomyositis rather than septic hip arthritis should be considered in children with a limp and hip and perineal pain, particularly girls with redness and swelling of the labium majus. In addition, imaging studies, including magnetic resonance imaging, should be performed for early diagnosis.

Severe rotavirus gastroenteritis in children older than 5 years after vaccine introduction.

INTRODUCTION: Rotavirus (RV) is the major pathogen responsible for acute gastroenteritis in infants. Since RV vaccines were introduced, a substantial decline in the incidence of severe RV infection has been reported. However, some burden still exists, even in developed countries, including Japan. METHODS: We retrospectively surveyed 380 patients hospitalized for acute gastroenteritis from 2015 to 2019. In 2019, additional detailed clinical information of 21 patients with RV gastroenteritis was obtained to evaluate the efficacy of the RV vaccine. Nine fecal samples from those patients were collected to detect the RV genotypes. RESULTS: Our data showed an increasing trend in hospitalizations for severe RV gastroenteritis in children older than 5 years. According to the Vesikari clinical severity scores in the older group (≥5 years), the gastrointestinal symptoms in vaccinated patients were less severe than those in unvaccinated patients (p = 0.014). The genotype analysis revealed that G9P[8]I1 was the major genotype in the recruited patients in 2019. CONCLUSIONS: This report warns that children older than 5 years could be affected by severe RV infection and suggests prompt intervention for this age group, similar to that in infants. In the new period in which the RV vaccine is included in Japanese national immunization programs beginning October 2020, continuous monitoring of patient clinical characteristics and RV epidemiology is required to determine the role of vaccines.

Mortality of Japanese patients with Leigh syndrome: Effects of age at onset and genetic diagnosis.

Leigh syndrome is a major phenotype of mitochondrial diseases in children. With new therapeutic options being proposed, assessing the mortality and clinical condition of Leigh syndrome patients is crucial for evaluating therapeutics. As data are scarce in Japan, we analysed the mortality rate and clinical condition of Japanese Leigh syndrome patients that we diagnosed since 2007. Data from 166 Japanese patients diagnosed with Leigh syndrome from 2007 to 2017 were reviewed. Patients' present status, method of ventilation and feeding, and degree of disability as of April 2018 was analysed. Overall, 124 (74.7%) were living, 40 (24.1%) were deceased, and 2 (1.2%) were lost to follow-up. Median age of living patients was 8 years (1-39 years). Median length of disease course was 91 months for living patients and 23.5 months for deceased patients. Nearly 90% of deaths occurred by age 6. Mortality rate of patients with onset before 6 months of age was significantly higher than that of onset after 6 months. All patients with neonatal onset were either deceased or bedridden. MT-ATP6 deficiency caused by m.8993T>G mutation and MT-ND5 deficiency induced a severe form of Leigh syndrome. Patients with NDUFAF6, ECHS1, and SURF1 deficiency had relatively mild symptoms and better survival. The impact of onset age on prognosis varied across the genetic diagnoses. The clinical condition of many patients was poor; however, few did not require mechanical ventilation or tube-feeding and were not physically dependent. Early disease onset and genetic diagnosis may have prognostic value.

Cerebral Autoregulation During Active Standing Test in Juvenile Patients with Instantaneous Orthostatic Hypotension.

Instantaneous orthostatic hypotension (INOH) is one of the main types of orthostatic dysregulation in children and adolescents. In patients with INOH arterial pressure drops considerably after active standing and is slow to recover. We investigated changes in cerebral oxygenation in the bilateral prefrontal cortex during an active standing test in juvenile INOH patients to evaluate changes in cerebral oxygen metabolism. We enrolled 82 INOH patients (mean age 13.8 ± 2.2 years, 52 mild and 30 severe patients) at Nihon University Itabashi Hospital from October 2013 to April 2018. We measured cerebral oxygenated hemoglobin, deoxygenated hemoglobin, and total hemoglobin levels in the bilateral prefrontal cortex using near-infrared spectroscopy during an active standing test. In severe INOH patients, cerebral oxygenation of the right prefrontal cortex remained constant when blood pressure dropped; however, de-oxy-Hb significantly increased. These findings confirm that there is asymmetrical autoregulation between the right and left prefrontal cortex.

Infantile cerebral infarction caused by severe diabetic ketoacidosis in new-onset type 1 diabetes mellitus.

Background Diabetic ketoacidosis (DKA) is a common complication of type 1 diabetes mellitus (T1DM). Infants and children with new-onset T1DM may present with DKA, and the risk of cerebral edema is high in infantile DKA. What is new? Neurological deterioration during an episode of DKA is usually attributed to cerebral edema and cerebrovascular accidents. However, cerebral infarction is a very rare complication in infantile DKA. Case presentation We describe a rare case of infantile cerebral infarction caused by severe DKA in a patient with new-onset T1DM. Conclusions Cerebral infarction is an important intracranial complication in infantile DKA. Careful observation and treatment for DKA during the first 24 h of therapy are necessary in infants with new-onset T1DM because the risk of cerebral infarction is highest during this timeframe.

Primary carnitine deficiency with severe acute hepatitis following rotavirus gastroenteritis.

Rotavirus infection is a major cause of gastroenteritis, which occurs mainly in children. Liver dysfunction due to rotavirus gastroenteritis has been reported; however, acute hepatitis due to this disease is very rare. We present a rare case in which rotavirus gastroenteritis led to sequential diagnosis of acute hepatitis and systemic primary carnitine deficiency (CDSP) in a 1-year-old girl. The patient's symptoms (hypoglycemia, hepatomegaly, and elevated levels of serum transaminases and creatinine kinase) suggested a steatosis causing liver dysfunction. She was initially considered to have a beta oxygenation defect or secondary carnitine deficiency caused by pivalic acid-containing antibiotics; however, repetitive carnitine analysis and free carnitine clearance measurement confirmed primary carnitine deficiency (carnitine transporter deficiency). Children with severe liver dysfunction due to rotavirus infection and presenting with liver steatosis should undergo blood acyl carnitine analysis to detect potential carnitine or other beta oxidation deficiencies, especially if newborn screening for these diseases is not available.

A case of confusional migraine with transient increased cerebral blood flow.

BACKGROUND: Confusional migraine is a rare type of migraine presenting as an acute confusional state. However, the mechanism of this confusional state remains unclear. SUBJECT AND METHODS: We examined an 11-year-old girl with confusional migraine, using electroencephalography, brain magnetic resonance imaging, cerebrovascular magnetic resonance angiography, and single-photon emission computed tomography to investigate cerebral blood flow changes. RESULTS: Our findings revealed vessel narrowing in the left middle and posterior cerebral artery territory, indicating vasospasm and suggesting that the confusion was caused by hypoperfusion. However, abnormal increased cerebral blood flow in the left middle and posterior cerebral artery territory was observed during the non-confusional state. CONCLUSION: The recorded cerebral blood flow changes are similar to those associated with migraine attacks, gradually changing from abnormally low to abnormally high during the confusional and post-confusional state.

Agraphia with reversible splenial corpus callosum lesion caused by hypoglycemia.

BACKGROUND: Neurological manifestations caused by hypoglycemia range from reversible focal deficits and transient encephalopathy to irreversible coma or death. Recently, high signal intensity lesions in the splenium of the corpus callosum on diffusion-weighted magnetic resonance imaging were reported in adults experiencing hypoglycemia. However, patients presenting with agraphia are rare. SUBJECT AND METHODS: We examined a 17-year-old left-handed female patient with type 1 diabetes who exhibited transient left agraphia with a reversible splenium lesion of the corpus callosum on diffusion-weighted imaging caused by hypoglycemia, which was improved with blood glucose management alone. CONCLUSION: This rare case indicates that agraphia, a sign of callosal disconnection syndrome, can result from a reversible splenial lesion of the corpus callosum caused by hypoglycemia.

Hypocarnitinemia Observed in an Infant Treated with Short-Term Administration of Antibiotic Containing Pivalic Acid.

Carnitine is a water-soluble amino acid derivative required for ß-oxidation of long-chain fatty acids. In carnitine cycle abnormalities and low carnitine states, fatty acid ß-oxidation is inhibited during fasting, resulting in hypoglycemia. Pivalic acid is a substance used in prodrugs to increase absorption of parent drugs, and antibiotics containing pivalic acid are frequently used as wide spectrum antibiotics for pediatric patients in Japan. Pivalic acid released after absorption is conjugated with free carnitine to form pivaloylcarnitine, which is then excreted in urine. As a consequence, long-term administration of pivalic acid containing antibiotics has been associated with depletion of free carnitine, inhibition of energy production and subsequent hypoglycemia. Here we report a case of a 23-month-old boy treated with an antibiotic containing pivalic acid for 3 days for upper respiratory tract infection. Laboratory data at referral indicated hypoglycemia, decreased free carnitine and elevated five-carbon acylcarnitine. Isomer separation confirmed the major component of increased five-carbon acylcarnitine to be pivaloylcarnitine, thereby excluding the possibility of a genetic metabolic disorder detected with similar acylcarnitine profile. The level of carnitine was normal when the antibiotic was not administered. Our case shows that the use of antibiotics containing pivalic acid in young children requires consideration of hypocarnitinemia, even with short-term administration.

A case of classical maple syrup urine disease that was successfully managed by living donor liver transplantation.

Classical MSUD is often fatal without appropriate medical interventions because of metabolic crisis. There are numerous reports suggesting the therapeutic potential of deceased donor liver transplantation for MSUD. However, the usefulness of LDLT for MSUD is unknown. We report a case of classical MSUD, which was successfully managed by LDLT from the patient's father at 1 year of age. Abnormal brain findings, which were cured with effective treatment, gradually disappeared after LDLT. The patient then developed normally. Findings from this case suggest the importance of LDLT for maintaining low leucine levels and subsequent normal neurological development. Although LDLT involves a modest surgical insult, LDLT with a related donor achieves acceptable leucine levels for life.

Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients.

Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy and early childhood. It is clinically diagnosed by typical manifestations and characteristic computed tomography (CT) or magnetic resonance imaging (MRI) studies. Unravelling mitochondrial respiratory chain (MRC) dysfunction behind LS is essential for deeper understanding of the disease, which may lead to the development of new therapies and cure. The aim of this study was to evaluate the clinical validity of various diagnostic tools in confirming MRC disorder in LS and Leigh-like syndrome (LL). The results of enzyme assays, molecular analysis, and cellular oxygen consumption rate (OCR) measurements were examined. Of 106 patients, 41 were biochemically and genetically verified, and 34 had reduced MRC activity but no causative mutations. Seven patients with normal MRC complex activities had mutations in the MT-ATP6 gene. Five further patients with normal activity in MRC were identified with causative mutations. Conversely, 12 out of 60 enzyme assays performed for genetically verified patients returned normal results. No biochemical or genetic background was confirmed for 19 patients. OCR was reduced in ten out of 19 patients with negative enzyme assay results. Inconsistent enzyme assay results between fibroblast and skeletal muscle biopsy samples were observed in 33% of 37 simultaneously analyzed cases. These data suggest that highest diagnostic rate is reached using a combined enzymatic and genetic approach, analyzing more than one type of biological materials where suitable. Microscale oxygraphy detected MRC impairment in 50% cases with no defect in MRC complex activities.

Severe Acute Subdural Hemorrhages in a Patient with Glutaric Acidemia Type 1 under Recommended Treatment.

Glutaric acidemia type 1 is a rare autosomal recessive disease caused by a deficiency of glutaryl-CoA dehydrogenase. Previous studies have reported subdural hemorrhage in untreated patients with glutaric acidemia type 1. However, there is only one report of severe acute subdural hemorrhage after minor head trauma in a patient with glutaric acidemia type 1 under guideline-recommended treatment. We report a second case of life-threatening severe acute subdural hemorrhage after a minor head trauma in a patient with glutaric acidemia type 1. This patient was previously diagnosed by newborn screening, and treatment began at 25 days of age. Early diagnosis and guideline-recommended treatment produce better outcomes for patients with glutaric acidemia type 1, although the risk of subdural hemorrhage remains.

Acute Focal Bacterial Nephritis Associated With Central Nervous System Manifestations: A Report of 2 Cases and Review of the Literature.

Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the kidney presenting as an inflammatory mass without frank abscess formation. In children, most patients with AFBN present with nonspecific conditions, such as fever, vomiting, and abdominal pain. A small number of reported cases are accompanied by neurological symptoms, including meningeal irritation, unconsciousness, and seizures. We experienced 2 rare cases of AFBN associated with central nervous system lesions. The first case was a 3-year-old girl who had neurological symptoms, including unconsciousness and seizures, with AFBN associated with acute reversible encephalopathy. The second case was a 5-year-old girl who had neurological symptoms, including unconsciousness, with AFBN accompanied by clinically mild encephalitis/encephalopathy with a reversible splenial lesion.

Extrapontine myelinolysis associated with severe hypernatremia in infancy.

Extrapontine myelinolysis (EPM) is an uncommon disorder in children, with few pediatric cases reported to date. We report the first case of an infant with EPM without central pontine myelinolysis (CPM) presenting with severe hypernatremia. On admission, the infant had impaired consciousness, mild dehydration, and severe hypernatremia (190 mmol/L). The following day, the patient developed abnormal involuntary movements. Brain magnetic resonance imaging (MRI) confirmed EPM without CPM. He recovered without sequelae, and clinical examinations were within normal limits approximately 6 months after discharge. Brain MRI at 1 year after onset showed complete disappearance of the previous EPM regions. To the best of our knowledge, this represents the youngest patient with EPM without CPM presenting with severe hypernatremia. Given that treatment for osmotic demyelination syndrome (ODS) is yet to be established, preventing the development of ODS is crucial.

Severe hypoglycemic encephalopathy due to hypoallergenic formula in an infant.

A 7-month-old girl was brought to hospital due to vomiting. Upon admission, she was in a convulsive state and stupor with extremely low blood glucose. Head computed tomography showed brain edema, and comprehensive treatment for acute encephalopathy was initiated immediately. Severe hypoglycemia, metabolic acidosis, elevation of ammonia and serum transaminases and creatine kinase suggested metabolic decompensation. Infusion of a high-glucose solution containing vitamins, biotin, and l-carnitine resolved the metabolic crisis quickly, but brain damage was irreversible. She was found to have been fed exclusively on a hypoallergenic formula (HF) for 7 months, although she was found later to be non-allergic. Evidence of inborn metabolic diseases was absent, therefore biotin deficiency and carnitine deficiency were concluded to be a consequence of reliance on a HF for a prolonged period. Health-care professionals should warn parents of the consequences of using HF.