Improvement in a post-stroke pediatric patient with hemiplegia: Use of a hand-arm bimanual intensive therapy with hybrid assistive limb.

Background: Pediatric stroke is a rare medical condition that often leads to long-lasting motor and cognitive impairments. Although therapies for adults after a stroke are well described, treatments for motor deficits following a pediatric stroke are yet to be investigated. We report a case of pediatric stroke in the chronic phase, in which a combination of novel treatments resulted in a significant improvement in physical function.

Early clinical signs and treatment of Menkes disease.

Menkes disease (MD) is an X-linked recessive disorder caused by mutations in . Patients with MD exhibit severe neurological and connective tissue disorders due to copper deficiency and typically die before 3 years of age. Early treatment with copper injections during the neonatal period, before the occurrence of neurological symptoms, can alleviate neurological disturbances to some degree.

Application of a wearable switch to perform a mouse left click for a child with mix type of cerebral palsy: a single case study.

Children with cerebral palsy may face difficulties using handheld pointing devices, due to involuntary muscle movements. This study aimed at describing the idea of the new wearable sensor switch and assessing its feasibility as an access solution in a case of mixed-type cerebral palsy. The study participant was a 17-year-old male with mixed-type cerebral palsy characterized by chorea-athetotic movements and bilateral spasticity with gross motor function classification system level V.

Pericarditis-complicated takotsubo cardiomyopathy in a patient with rheumatoid arthritis.

A 64-year-old woman with medication-controlled rheumatoid arthritis (RA) was admitted to our hospital complaining of chest pains. An electrocardiogram showed elevated ST-segments in the inferior leads, and inverted T-waves in the left precordial leads. Left ventriculography demonstrated apical ballooning, and cardiac magnetic resonance imaging demonstrated apical ballooning of the left ventricle, and moderate pericardial effusion.

Cholesterol Metabolism Is Enhanced in the Liver and Brain of Children With Citrin Deficiency.

Context: Citrin-deficient infants present neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), which resolves at 12 months. Thereafter, they have normal liver function associated with hypercholesterolemia, and a preference for lipid-rich carbohydrate-restricted diets. However, some develop adult-onset type II citrullinemia, which is associated with metabolic abnormalities.

Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver Function During the Apparently Healthy Period.

Background: Citrin (mitochondrial aspartate-glutamate transporter) deficiency causes the failures in both carbohydrate-energy metabolism and the urea cycle, and the alterations in the serum levels of several amino acids in the stages of newborn (NICCD) and adult (CTLN2). However, the clinical manifestations are resolved between the NICCD and CTLN2, but the reasons are still unclear. This study evaluated the serum amino acid profile in citrin-deficient children during the healthy stage.

Renal insufficiency mimicking glutaric acidemia type 1 on newborn screening.

Background: Glutaryl carnitine (C5DC) in dried blood spots is used as a biomarker for glutaric aciduria type 1 (GA-1) screening. C5DC, however, is the only screening marker for this condition, and various pathological conditions may interfere with C5DC metabolism. Recently, C5DC elevation has been reported in cases of renal insufficiency.

2'-O-Methyl RNA/Ethylene-Bridged Nucleic Acid Chimera Antisense Oligonucleotides to Induce Dystrophin Exon 45 Skipping.

Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease characterized by dystrophin deficiency from mutations in the gene. Antisense oligonucleotide (AO)-mediated exon skipping targets restoration of the reading frame to allow production of an internally deleted dystrophin protein with functional benefit for DMD patients who have out-of-frame deletions. After accelerated US approval of eteplirsen (Exondys 51), which targets exon 51 for skipping, efforts are now focused on targeting other exons.

Circulating tricarboxylic acid cycle metabolite levels in citrin-deficient children with metabolic adaptation, with and without sodium pyruvate treatment.

Citrin deficiency causes adult-onset type II citrullinemia (CTLN-2), which later manifests as severe liver steatosis and life-threatening encephalopathy. Long-standing energy deficit of the liver and brain may predispose ones to CTLN-2. Here, we compared the energy-driving tricarboxylic acid (TCA) cycle and fatty acid β-oxidation cycle between 22 citrin-deficient children (age, 3-13years) with normal liver functions and 37 healthy controls (age, 5-13years).

Next-generation sequencing discloses a nonsense mutation in the dystrophin gene from long preserved dried umbilical cord and low-level somatic mosaicism in the proband mother.

Duchene muscular dystrophy (DMD) is a progressive muscle wasting disease, caused by mutations in the dystrophin (DMD) on the X chromosome. One-third of patients are estimated to have de novo mutations. To provide in-depth genetic counseling, the comprehensive identification of mutations is mandatory.

Impact of real-time three-dimensional transesophageal echocardiography on procedural success for mitral valve repair.

Background: For mitral valve repair, minimally invasive cardiac surgery as well as transcatheter valvular intervention have been developed. Under these conditions, three-dimensional transesophageal echocardiography (3D-TEE) plays a key role for planning the surgical treatment strategy. However, few data exist regarding the role of 3D-TEE in mitral valve repair.

Phosphorothioate modification of chimeric 2´-O-methyl RNA/ethylene-bridged nucleic acid oligonucleotides increases dystrophin exon 45 skipping capability and reduces cytotoxicity.

Backgrounds: Antisense oligonucleotide (AO)-mediated exon skipping is the most promising way to express internally deleted dystrophin in Duchenne muscular dystrophy (DMD), by correcting the reading frame of dystrophin mRNA. An antisense chimeric oligonucleotide consisting of 2´-O-methyl RNA and ethylene-bridged nucleic acid (ENA), targeting exon 45 of the dystrophin gene, AO85, has been shown to induce exon 45 skipping efficiently. Since phosphorothioate (PS)-modification of AO85 has never been explored, we produced a PS-modified AO85 (AO88) and examined its exon skipping capability and cytotoxicity.

Relationship between stature and tibial length for children with moderate-to-severe cerebral palsy.

Objective: To derive the equation for estimating stature, based on tibial length, for children with moderate-to-severe cerebral palsy (CP) and lower limb joint contracture or scoliosis.

Methods: The participants (3-12-years-old) included 50 children with moderate-to-severe CP (mean age, 8.3±2.

Identical deletion at 14q13.3 including PAX9 and NKX2-1 in siblings from mosaicism of unaffected parent.

By screening patients with undiagnosed multiple congenital anomalies and intellectual disability using array-comparative genomic hybridization, we identified an 884 kb heterozygous microdeletion at 14q13.3 in two siblings presenting with oligodontia, hypothyroidism and persistent pulmonary hypertension of the newborn, resulting from their parental gonosomal mosaicism. Among the six genes included in the deletion, haploinsufficiency of PAX9 and NKX2-1 was probably associated with their phenotypes.

Changes in body weight and height in survivors of Menkes disease.

Objective: To explore the changes in the body weight and height of Menkes disease (MNK) patients treated with long-term copper-histidine.

Methods: A survey involving a retrospective review of medical records or summaries of MNK patients was conducted. Patients were 44 males born after 1994, and their feeding method and genetic analysis of the ATP7A gene were reviewed.

A novel splicing silencer generated by DMD exon 45 deletion junction could explain upstream exon 44 skipping that modifies dystrophinopathy.

Duchenne muscular dystrophy (DMD), a progressive muscle-wasting disease, is mostly caused by exon deletion mutations in the DMD gene. The reading frame rule explains that out-of-frame deletions lead to muscle dystrophin deficiency in DMD. In outliers to this rule, deletion junction sequences have never previously been explored as splicing modulators.

Association of a vascular endothelial growth factor polymorphism with the development of bronchopulmonary dysplasia in Japanese premature newborns.

Our objective was to correlate vascular endothelial growth factor (VEGF) genetic polymorphisms with the risk of bronchopulmonary dysplasia (BPD) development in premature newborns. Fifty-five newborns with BPD (BPD: median gestational age [GA]: 27 weeks, birthweight [BW]: 786 g) and 42 newborns without BPD (non-BPD: median GA: 29 weeks, BW: 1,165 g), who were born at <32 weeks gestational age and were admitted to Kobe University Hospital, were included. BPD was defined as oxygen dependency at 36 weeks postmenstrual age.

[Clinical manifestations of three neonates with family histories of Menkes disease].

Objective: To examine indications for the early diagnosis of Menkes disease (MD).

Methods: We compared clinical examination results of 3 neonate males with family histories of MD who were at risk of being affected (1 infant was affected and 2 were unaffected).

Results: Kinky hair, a characteristic shown by MD patients, was observed just after birth in the affected infant; however, this characteristic was extremely mild and easy to miss.

Standard values for the urine HVA/VMA ratio in neonates as a screen for Menkes disease.

Background: Menkes disease is a lethal disorder associated with copper metabolism. Although early treatment with copper-histidine injections can improve outcomes, early diagnosis is difficult because the clinical features of Menkes disease are subtle or do not manifest in affected neonates. Previous report stated that the low activity of dopamine β-hydroxylase, a copper-dependent enzyme, leads to increases in the urine homovanillic acid/vanillylmandelic acid (HVA/VMA) ratios in patients with Menkes disease, and indicated that a urine HVA/VMA ratio cut-off value of >4 is useful in screening for Menkes disease.

Rapid progression of neuromuscular disorder related cardiomyopathy in a young patient.

An 11-year and 3-month-old boy with a neuromuscular disorder was admitted for dyspnea. Echocardiography revealed severe left ventricular dysfunction with an ejection fraction (EF) of 17%. However, the EF had been 57% when the patient was 10 years and 9 months old.

Differences in carrier frequency between mothers of Duchenne and Becker muscular dystrophy patients.

Duchenne and Becker muscular dystrophies (DMD/BMD) are X-linked inherited muscular disorders caused by mutations in the dystrophin gene. Two-thirds of DMD cases are thought to be caused by inheritance from carrier mothers and this study aimed to clarify and compare the carrier frequency of mothers of DMD and BMD patients according to the mutation type. We included 139 DMD and 19 BMD mothers.

Childhood-onset hereditary pancreatitis with mutations in the CT gene and SPINK1 gene.

Hereditary pancreatitis (HP) is an autosomal-dominant gene disorder. The affected genes have been identified as the cationic trypsinogen (CT) gene and the serine protease inhibitor Kazal type 1 (SPINK1) gene. These gene abnormalities alone, however, do not necessarily regulate the onset or severity of pancreatitis, suggesting the involvement of other gene abnormalities and environmental factors.