Long-term survival of a patient with acute neonatal-onset metabolic encephalopathy with carbamoyl phosphate synthetase 1 deficiency.

OBJECTIVE: Long-term survival of patients with neonatal-onset carbamoyl-phosphate synthetase 1 deficiency (CPS1D), an autosomal recessive disorder characterized by repeated, life-threatening hyperammonemia, is rare. We describe the diagnosis and clinical management of a teenager with neonatal-onset CPS1D who did not undergo therapeutic liver transplantation. CASE REPORT: Following emergent neonatal therapy, the patient was diagnosed with CPS1D based on clinical, radiological, biochemical and genetic analyses. Her clinical course, neurobehavioral development and therapeutic interventions are presented and discussed. RESULTS: Born from nonconsanguineous parents, the proband underwent phototherapy for neonatal jaundice, associated with acute encephalopathy, apnea and cerebral edema. Based on blood and urinary biochemical abnormalities, neonatal-onset CPS1D was diagnosed. Her hyperammonemia was corrected by hemodialysis, followed by sodium benzoate, L-arginine, levocarnitine and protein-free diet therapy. Because of a relapse and persistent neurobehavioral regression by age 1, a planned liver transplantation was cancelled. At age 10, sodium phenylbutyrate was substituted as ammonia scavenger. Genetic testing revealed compound heterozygote c.2359C>T (R787X) and c.236+6T>C variants of CPS1, confirming her diagnosis. Despite severe neurological sequelae, the patient is 16 and in stable condition. CONCLUSIONS: Our case suggests that early hemodialysis and pharmacologic interventions for acute neonatal hyperammonemia can improve the prognosis of patients with neonatal-onset CPS1D.

Efficacy and Safety of Salmeterol/fluticasone Combination Therapy in Infants and Preschool Children with Asthma Insufficiently Controlled by Inhaled Corticosteroids.

BACKGROUND: Clinical evidences of inhaled salmeterol/fluticasone propionate combination (SFC) therapy are insufficient in early childhood asthma. OBJECTIVES: To examine the effects of SFC50, a combination product of salmeterol xinafoate (50 µg/day) and fluticasone propionate (100 µg/day), in infants and preschool children with asthma. METHODS: The study was conducted at 31 sites in Japan. 35 patients (6 months to 5 years old) with asthma insufficiently controlled by inhaled corticosteroids (100 µg/day) were initiated to treat with SFC50 twice a day for 12 weeks with pressurized metered dose inhalers. The efficacy of SFC50 was assessed using nighttime sleep disorder score as the primary endpoint and the other efficacy measurements. The safety measurement included the incidences of adverse event (AE). RESULTS: Mean patient age was 3.1 years, and 94.2% had mild-to-moderate persistent asthma (atopic type: 65.7%). Nighttime sleep disorder scores, assessed by a nighttime sleep diary, significantly decreased after treatment with SFC50 throughout the study period (p<0.01). SFC50 also significantly improved other efficacy outcomes including asthma symptom score, frequency of short-acting beta-agonist treatment, frequency of unscheduled visits to clinic, frequency of exacerbation due to virus infection, asthma control score and patient QOL score (p<0.01). AEs of cold, upper respiratory inflammation and asthmatic attack occurred in each of the 3 patients (8.6%); however, these were not regarded as treatment-related AEs. CONCLUSIONS: SFC50 improved nighttime sleep disorder score and other efficacy outcome measures with no safety concerns. The results suggest that SFC50 treatment is useful to control the mild-to-moderate asthma in infant and preschool-aged children.

Long-term survival of full trisomy 13 in a 14 year old male: a case report.

Long term survival for the cases of trisomy 13 into over a first decade is very rare. We reported here the case of a 14-year-old male karyotype with full type of trisomy 13. In this clinical phenomenon, the case had typical facial, finger and limb anomalies for trisomy 13. Arterial septal defect and patent ductus arteriosus were recognized using ultrasonography after birth. Major cerebral malformation such as holoprosencephaly or cerebellar hypoplasia were also not revealed. After 5 months of his age, artificial ventilation therapy for dyspnea associated with laryngomalacia was required. A tracheotomy was performed at 6 months of his age. After 12 years old, intractable partial epilepsy was recognized. For his partial seizures, a treatment with a combination of two anti-epileptic drugs, valproic acid and levetiracetam, were advised. Now he is alive for 14-years-old and he is the 4th longest surviving patient with full karyotype of trisomy 13.

Drop episodes improved after tracheotomy: a case of Coffin-Lowry syndrome associated with obstructive sleep apnea syndrome.

Some cases of Coffin-Lowry syndrome recognized episodic drops and it tended to be intractable for medical treatment. We reported here a patient with the Coffin-Lowry syndrome associated with obstructive sleep apnea syndrome (OSAS). The patient had epileptic seizures and drop attacks only during night-time and it was not recognized during the daytime. His sleep-induced electroencephalogram was normal. At 12-years old of his age, his OSAS was worse, so we performed a tracheotomy. Notably after the operation, his epileptic episodes were disappeared.

Del(18)(q12.2q21.1) syndrome: a case report and clinical review of the literature.

The terminal deletion of the long arm of chromosome 18 is relatively common among cytogenetic abnormalities, which occur incidentally in approximately 1 in 40,000 live births. Proximal interstitial deletions of the long arm of chromosome 18 are less frequent. The critical region on chromosome 18 of this syndrome is del(18)(q12.2q21.1) and has recently been recognized as a new clinical entity. We describe a 8-year-old boy with developmental delay, obesity, and epilepsy, with characteristic facial anomalies in whom G-banding chromosome analysis revealed a unique karyotype of 46, XY, del(18)(q12.2q21.1). The patient was diagnosed with interstitial deletion chromosome 18q-syndrome. He received weight control therapy from a medical dietitian. For his epilepsy, he was administered oral carbamazepine at 4 mg/kg/day. At age six, he entered a special needs elementary school. After entering school, he often showed hyperkinesis, and was diagnosed with attention deficit hyperactivity disorder with mild mental retardation. Because patients with only del(18)(q12.2q21.1) have no serious associated malformations, physicians should be aware that even adult patients may have 18q-syndrome. Therefore, if epilepsy occurs in patients with minor facial anomalies, psychomotor retardation, obesity, and the possibility of 18q-syndrome with del(18)(q12.2q21.1) should be kept in mind, and chromosome testing should be performed.

Treatment with mild brain hypothermia for cardiopulmonary resuscitation after myoclonic seizures in infant with robertsonian type of trisomy 13.

Congenital chromosomal abnormality with trisomy 13 is known to be associated with poor life prognosis and lethal. Therefore, physician advice the patients be kept in intensive treatment with resuscitation and state of the art intensive care when sudden change in the general condition with this trisomy is observed. We report herein, the treatment with mild brain hypothermia therapy for cardiopulmonary resuscitation after myoclonic seizures in infant with Robertsonian type of trisomy 13 in intensive care unit. Our study indicated that brain hypothermia therapy and steroid pulse therapy on an infant who was believed to have post-resuscitation hypoxic encephalopathy was highly effective as the patient's general condition recovered to the original state after four months.

Acute encephalopathy associated with hemolytic uremic syndrome caused by Escherichia coli O157: H7 and rotavirus infection.

We reported a case of a 22-months child with hemolytic uremic syndrome associated with encephalopathy. As the cause of this case, the involvements of verotoxin 1 and 2 caused by O157: the H7 strain of the enterohemorrhagic Escherichia coli and rotavirus were presumed. We administered brain hypothermic therapy and steroid pulse therapy in the intensive care unit, but we were not able to save his life and the child died on the 6th day from the onset.

Serial EEG study in a girl with Landau-Kleffner syndrome associated with continuous spikes and waves during slow sleep.

Landau-Kleffner syndrome (LKS) is rare epileptic encephalopathy in childhood, characterized by both acquired epileptic aphasia and abnormal epileptiform discharges in electroencephalogram (EEG). We herein report a serial EEG study in LKS. A 22-month old girl was referred to our hospital because of frequently partial seizures in her left upper limb. On EEG performed and multiforcal spikes were recognized. Oral treatment of carbamazepine was started but her seizures were not controlled. Her language ability did not progress after 2 years of her age. At age 4 years, carbamazepine was switched to valproic acid, leading to reduction in the frequency of seizure episodes. She was able to speak two-word sentences at 4 years of age, but her word output gradually decreased. At 5 years of age, addition of zonisamide further reduced the frequency of seizure episodes, but failed to achieve complete control of seizures. She increasingly asked for questions to be repeated. Auditory brainstem response testing performed at the department of otolaryngology revealed normal hearing ability. She was diagnosed as having intellectual deficits with an intelligence quotient (IQ) of 61 at 7 years of age. The EEG at 8 years of age showed continuous spikes and waves during slow sleep (CSWS), leading to a diagnosis of LKS. After age 11 years, the CSWS on EEG improved without requiring a change in antiepileptic drugs (AEDs). Treatment with the oral AEDs was discontinued at 13 years of her age. Her IQ at 13 years of age was in the low 70s.

An infant with steroid-refractory cytomegalovirus-associated ADEM who responded to immunoglobulin therapy.

Acute disseminated encephalomyelitis (ADEM) develops via an immunological mechanism. We encountered a 10-month-old infant with a rare pathogenesis of cytomegalovirus (CMV)-related ADEM. The patients complaints were; protracted fever; consciousness disorder; and affected cervical stability. Cerebral magnetic resonance imaging (MRI) 9 days after onset, revealed a disseminated lesion, suggesting ADEM. Pulse therapy with methylprednisolone at 30 mg/kg was performed for 3 days. However, its clinical efficacy was not marked. Therapy with immunoglobulin (IVIg) at 400 mg/kg/day was started 15 days after onset, and continued for 5 days. This markedly improved the consciousness level and muscle strength, and the infant was discharged without neurological sequelae. ADEM showed a monophasic course, and the infant's subsequent growth has been favorable. Altough the number of case reports is small, massive-IVIg therapy should be considered in patients with steroid-refractory ADEM, as demonstrated in this case study.

Brain hypothermia therapy for status epilepticus in childhood.

OBJECTIVE: At the Dokkyo Medical University Hospital, we introduced a brain hypothermia therapy protocol for treating childhood status epilepticus and acute encephalitis/encephalopathy in 2004. PATIENTS AND METHODS: This protocol focuses on infants with a minimum age of six months or 7.5 kg in weight. Applicable diseases include acute encephalitis/encephalopathy occurring from status epilepticus or seizures lasting for 30 minutes or longer, in cases such as near drowning, hypoxic-ischemic encephalopathy, post-resuscitation encephalopathy, cardio-respiratory arrest, severe head injury, or other diagnoses in which the pediatric neurologist recognizes the possibility of neurological complications. Brain hypothermia therapy is managed within the intensive care unit (ICU). RESULTS: The target body temperature is a bladder or rectum temperature of 34.0 to 35.0 degrees. This body temperature is reduced to the target temperature within six hours of the seizures. Hypothermia is maintained for 48 hours and concomitant steroid pulse therapy may be used at appropriate times. Sodium thiopental is used to sedate and rewarming is carried out at 0.5 degrees per 12 hours. Osmotic diuretics, muscle relaxants and circulatory antagonists may be concomitantly used at appropriate times. CONCLUSIONS: This paper reviews the brain hypothermia therapy protocol.

Partial epilepsy and developmental delay in infant with ring chromosome 14.

Ring chromosome 14 (r14) is clinically characterized by early-onset epilepsy, mental retardation, delayed speech, microcephaly, extremely mild facial dysmorphisms and ophthalmologic abnormalities. We report a case presenting with partial seizures and delayed development in infancy in which r14 was diagnosed based on chromosomal analysis. The patient was a girl with a normal family and delivery history. Afebrile generalized convulsions developed at age 9 months, and phenobarbital was started, but was changed to zonisamide due to impaired liver function. Chromosome analysis led to a diagnosis of 46, XX, r(14) (p11.2q32.3). At age 5 years, while under treatment with zonisamide and clobazam, epilepsy was characterized by multiple daily episodes of complex partial seizures. Although there are no consistent brain MRI or electroencephalogram findings, experienced pediatric neurologists can make a diagnosis based on facial dysmorphisms. When refractory epilepsy is encountered in infancy with developmental delay of unknown cause, chromosome analysis should be performed.

Diagnosis of sex chromosomal abnormalities in neonatal intensive care units.

Neonates are hospitalized in the neonatal intensive care unit for complications arising during delivery or for the treatment of congenital anomalies. Some anomalies may warrant chromosomal analysis. We investigated all cases of neonates hospitalized in the NICU at Dokkyo Medical University Hospital between January 1990 and May 2011. Over the study period of 21 years and 5 months, 169 of 6,159 neonates (2.74%) were diagnosed with chromosomal abnormalities. Autosomal chromosomal aberrations were observed in 165 neonates (2.68%), and sex chromosome abnormalities in only 4 neonates (0.07%). Compared with previous studies, we found a much lower prevalence of sex chromosome abnormalities, despite a similar overall prevalence of chromosomal abnormalities. This seems to be due to the fact that sex chromosome abnormalities are likely to be clinically invisible in the NICU.

Impact of leptin and leptin-receptor gene polymorphisms on serum lipids in Japanese obese children.

AIM: Leptin is one of the factors affecting serum lipid profile. We investigated the association between serum lipids and leptin/leptin receptor (LEPR) gene polymorphisms in obese Japanese children. METHODS: One hundred and thirty-six obese children (99 males and 37 females, relative weight over than 20%) from 5 to 17 years of age were recruited from 10 institutes. Four known polymorphisms in leptin gene [(+19)A G, (-2548)G A, (-188)C A, (-633)C T] and four known polymorphisms in LEPR gene [Lys109Arg, Gln223Arg, Pro(G)1019Pro(A), Ser(T)343Ser(C)] were determined using polymerase chain reaction-restriction fragment length polymorphism-based analyses. RESULTS: No associations were found between leptin gene polymorphisms and serum lipid profile. On the other hand, Lys109Arg and Ser343Ser polymorphism in LEPR gene, but not Gln223Arg or Pro1019Pro, had significant relationships with serum lipid profile; lower total and low-density lipoprotein cholesterol levels in Arg109Arg homozygotes, and lower TG levels in Ser343Ser(C/C) homozygotes. In addition, LEPR gene also associated with relative weight; Arg109Arg homozygotes had higher relative weight and Ser343Ser(C/C) homozygotes had lower one. CONCLUSION: These results suggest that LEPR gene polymorphisms may partly contribute to serum lipid profile in obese children.