Multiple mutations in Kir6.x and SURx genes have implicated ATP-sensitive potassium (K_ATP) channels and, as a result, have led to diverse diseases, ranging from diabetes and hyperinsulinism to cardiac arrhythmias and cardiovascular disease. These diseases are referred to as K_ATP channelopathies. Recently, Cantú syndrome (CS), which was found to be caused by mutations in the ABCC9 or KCNJ8 gene, was newly added to the list of K_ATP channelopathies. CS is a rare multi-organ disease characterized by congenital hypertrichosis, characteristic face, persistent ductus arteriosus, cardiomegaly, intrauterine overgrowth, and skeletal abnormalities. Congenital hypertrichosis and coarse face have been confirmed in all CS patients. On the other hand, cardiovascular and skeletal abnormalities vary widely in severity, even in some familial cases and in isolated cases sharing the same mutation. Information about genotype-phenotype correlations in CS are described here.

  Objective: We examined the short-term efficacy and safety of rufinamide (RFN) in patients with Lennox-Gastaut syndrome (LGS). Methods: We performed a retrospective review of clinical records of patients with LGS who started RFN treatment between July 2013 and June 2014 at the Hokkaido Medical Center for Child Health and Rehabilitation and Midorigaoka Ryo-iku-en. Efficacy and safety were evaluated when the patients had completed three months of treatment. Patients were classified into four categories according to percent seizure reduction : remission (seizure-free), response (seizure reduction≥50%), no change (seizure reduction<50% or increase) and aggravation (seizure increase≥50%). Responder rate (RR) was the percentage of patients with≥50% decrease in seizure frequency. Results: Thirteen LGS patients (8 males, 5 females) were studied. The efficacy for tonic seizures (13 patients) was remission 1 patient, response 3 patients, no change 8 patients and aggravation 1 patient, with RR of 30.8%. Two patients discontinued LGS due to seizure aggravation. Four patients experienced transient remission. For generalized tonic clonic seizures (2 patients), 1 patient achieved remission and 1 patient showed no change. Two patients of atonic seizures showed no change. Of 2 patients of atypical absence, 1 patient showed response and 1 patient no change. Eight patients had adverse effects such as somnolence (6 patients), sleep disturbance (1 patient), and appetite loss (4 patients) including weight loss in 2 patients. There were no severe adverse effects and no discontinuation due to adverse effects. Conclusions: Short-term effectiveness for tonic seizures was observed when patients with LGS were treated with RFN, with transient remission in some patients. We consider that RFN is worth trying in patients with LGS due to its efficacy for tonic seizures and absence of severe adverse effects.

  Objective: Nutritional management in children with medically dependent severe motor and intellectual disabilities (SMID) is difficult. SMID children with respirator support sometimes showed obesity in spite of proper nutrition. The optimal energy intake in these children remains unclear. The objective of this study is to determine the features of body composition and the optimal calorie intake in children with respirator-dependent SMID due to severe hypoxia. Methods: The study was a retrospective chart review of five children with respirator-dependent SMID due to severe hypoxia. They were treated between 2012 and 2015 at the National Center for Child Health and Development in Tokyo, Japan. Their ages ranged from one to nine years. All patients were clinically stable under continuous mechanical ventilation. Body composition including body fat percentage (%Fat), muscle mass (MM) and fat-free mass (FFM) were measured by a multi-frequency bioelectrical impedance analysis (BIA) (InBody S20^®). When necessary, adjustments for calorie intake were made. Results: %FAT was high (range, 40 to 70%) and MM was low, indicating that all children were under excessive nutrition. A markedly decrease in FFM was also observed. After the adjustment, daily calorie intake was maintained at 210 to 350 kcal/day. Daily calorie intake per FFM ranged from 25 to 42 kcal/kg/day. Conclusions: The children’s body composition revealed that FFM was decreased. As FFM is a major influencing factor for basal metabolic rate, FFM-based calorie adjustment is useful to determine the optimal calorie intake in children with respirator-dependent SMID due to severe hypoxia. Nutritional assessment using BIA is recommended in such children.

  Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration or loss of anterior horn cells in the spinal cord. The SMN1 gene is considered to be responsible for SMA, because 95% of SMA patients show homozygous deletion of SMN1. In this study, we examined the clinical course of an SMA type 1 patient who retains one allele of SMN1, identifying an intragenic mutation in the retained allele.

  The patient was a Japanese boy with no family history of neuromuscular disorders. He showed generalized muscle weakness and respiratory failure from the neonatal period. He underwent non-invasive positive pressure ventilation at 20 days old. His respiratory failure rapidly deteriorated, and endotracheal intubation-positive pressure ventilation was needed at 3 months old, followed by tracheostomy-positive pressure ventilation at 6 months old. For diagnosis, the SMN1 deletion screening test was performed, but the result was negative. Further analysis showed absence of one SMN1 allele, and presence of an intragenic mutation (c.819_820insT) in the retained SMN1 allele that disrupts the C-terminal domain of the SMN protein. He was subsequently diagnosed as having SMA type 1 with a compound heterozygous genotype. We conclude that an intragenic mutation in the retained SMN1 allele caused SMA in the index patient, and suggest that this mutation is a critical factor in determining disease severity.

  X-linked lissencephaly with ambiguous genitalia (XLAG) syndrome is a disorder associated with severe intellectual disability and intractable epilepsy. Intractable diarrhea is also observed frequently. At present, pathogenic background of diarrhea is not revealed and the essential treatment has not yet established. We encountered a patient with XLAG, who showed intractable diarrhea. Lactose removed hypoallergenic milk and somatostatin analogs were ineffective. For enteral nutrition was impossible, a tunneled central venous catheters was inserted to obtain a sustained parenteral nutrition management. However, catheter-related bloodstream infections were repeated in a short period of time. Thus, we introduced ethanol lock therapy for infectious disease prevention purposes. As a result, we succeeded continuous treatments with preserving the catheter.

  Benign familial infantile epilepsy (BFIE) is characterized by non-febrile focal seizures, which sometimes evolve to secondarily generalized seizures and are usually resolved in the second year. Proline-rich transmembrane protein 2 (PRRT2) is confirmed as the major cause of BFIE, familial paroxysmal kinesigeneic dystonia (PKD) and infantile convulsions and choreoathetosis (ICCA) syndrome. We examined a female patient with a hot spot mutation of PRRT2 gene. She had recurrent tonic seizures when she was three months old. The seizures were controlled by several kinds of anticonvulsants. Then, she had several times of focal seizures daily at nine months old. However, the seizures were stopped by small amounts of carbamazepine. Later, when she was two years old, she experienced frequent motor seizures characterized by truncal flexion and swaying the body with partially disturbed consciousness. Her father also had the same PRRT2 gene mutation and non-febrile seizures in infancy. The patient had mild to moderate mental retardation, whereas her father was mentally normal. Therefore, the patient revealed a quiet different phenotype from that of her father as a carrier of the same PRRT2 gene mutation. We speculate that the PRRT2 mutation had caused the BFIE-like seizures both in the patient and her father, whereas other unknown genetic factors specific for the patient might be associated with the atypical seizures observed only in her.