Succinyl-CoA:3-oxoacid CoA transferase (SCOT, gene symbol
OXCT1
) deficiency is an autosomal recessive disorder in ketone body utilization that results in severe recurrent ketoacidotic episodes in ...infancy, including neonatal periods. More than 30 patients with this disorder have been reported and to our knowledge, their heterozygous parents and siblings have had no apparent ketoacidotic episodes. Over 5 years (2008–2012), we investigated several patients that presented with severe ketoacidosis and identified a heterozygous
OXCT1
mutation in four of these cases (Case1 p.R281C, Case2 p.T435N, Case3 p.W213*, Case4 c.493delG). To confirm their heterozygous state, we performed a multiplex ligation-dependent probe amplification analysis on the
OXCT1
gene which excluded the presence of large deletions or insertions in another allele. A sequencing analysis of subcloned full-length SCOT cDNA showed that wild-type cDNA clones were present at reasonable rates to mutant cDNA clones. Over the following 2 years (2013–2014), we analyzed
OXCT1
mutations in six more patients presenting with severe ketoacidosis (blood pH ≦7.25 and total ketone body ≧10 mmol/L) with non-specific urinary organic acid profiles. Of these, a heterozygous
OXCT1
mutation was found in two cases (Case5 p.G391D, Case6 p.R281C). Moreover, transient expression analysis revealed R281C and T435N mutants to be temperature-sensitive. This characteristic may be important because most patients developed ketoacidosis during infections. Our data indicate that heterozygous carriers of
OXCT1
mutations can develop severe ketoacidotic episodes in conjunction with ketogenic stresses.
Abstract Pertussis is characterized by intense, prolonged coughing in children often followed by a distinctive whooping sound on inspiration. However, the clinical manifestations and natural course ...of pertussis in disabled children are largely unknown. We experienced a case of pertussis in a disabled girl who had previously undergone a tracheostomy and laryngotracheal separation. She presented with increased tracheal secretions and required hospitalization but did not develop a cough. Pertussis was suspected from the sputum Gram stain, which revealed numerous, short gram-negative rods that did not grow on chocolate agar. A nucleic acid amplification test was positive for Bordetella pertussis and the patient improved on azithromycin. Pertussis may present without its cardinal symptoms in disabled children.
Early onset pediatric ulcerative colitis (EO-UC) is distinguished from late-onset pediatric ulcerative colitis (LO-UC) by the effects of genetic predisposition, but there have been few reports on the ...clinical features of EO-UC in Asia.
To describe and compare the presentation and disease course of EO-UC (age range, 0-7 years) with those of LO-UC (age range, 8-15 years), we retrospectively analyzed 63 children with UC who had been diagnosed between January 2004 and March 2014 at Saitama Children's Medical Center in Japan.
Ten patients (16%) had EO-UC, and 53 (84%) had LO-UC. All patients in the EO-UC group and 70% in the LO-UC group had pancolitis (P = 0.05). The period from onset to diagnosis was 9.0 ± 14.1 months for EO-UC and 2.6 ± 3.5 months for LO-UC (P < 0.01). The prevalence of extra-intestinal complications at diagnosis was significantly higher for EO-UC than for LO-UC (50% vs 11%, respectively; P < 0.01). There were no significant differences in the use of corticosteroids, immunomodulators, immunosuppressants, or surgical risk between the groups but, in the EO-UC group, only one patient was treated with cytapheresis and none was treated with anti-tumor necrosis factor (TNF-α) antibodies.
The EO-UC group had a higher incidence of pancolitis, longer diagnostic delay, and more extra-intestinal manifestations than the LO-UC group. Diagnosis and treatment may therefore be slightly more difficult for EO-UC than for LO-UC.
We encountered a patient with mitochondrial trifunctional protein deficiency in whom the corresponding mutations were not identified by a DNA panel for newborn screening for targeted diseases. After ...diagnosis confirmation by an enzyme assay and immunoblotting using the autopsied liver, the re-evaluation of the panel data indicated a heterozygous deletion of exons 6-9 that was later confirmed at the genomic level. cDNA analysis also identified exonization of the 5' region of intron 9 caused by a deep intronic mutation, c.811 + 82A>G.
Abstract Intractable diarrhea is a major symptom of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome and associated with autoantibodies against enterocytes. Although ...autoimmune enteropathy (AIE)-related 75 kDa antigen (AIE-75) is a prominent autoantigen involved in the enteropathy associated with IPEX syndrome, some patients with this syndrome demonstrated autoantibody recognizing a 95 kDa protein rather than AIE-75 in the small intestine. We, herewith, identified villin, an actin-binding protein, as the 95 kDa antigen. Four of five sera from patients with IPEX syndrome reacted with a fusion protein of glutathione-S-transferase and full length villin (GST–villin), whereas only three of 98 control sera weakly reacted with GST–villin. Anti-AIE-75 antibody was detected in all five IPEX sera but not in normal or control disease sera. We conclude that both AIE-75 and villin appear to be brush border autoantigens in IPEX syndrome and could be used for the diagnosis of AIE in patients with presumptive IPEX syndrome.
It is important to assess pediatric patients for nutritional deficiency when they are receiving specific interventions, such as enteral feeding. We focused on measurement of C0 and ...3-hydroxyisovalerylcarnitine (C5-OH) with tandem mass spectrometry (MS/MS), which is performed as part of the newborn mass screening. The purpose of this study was to investigate the usefulness of MS/MS for screening carnitine and biotin deficiencies.
Forty-two children (24 boys, 18 girls) were enrolled between December 2013 and December 2015. Blood tests, including measurement of serum free carnitine via the enzyme cycling method, and acylcarnitine analysis on MS/MS of dried blood spot (DBS), were performed for the evaluation of nutrition status.
Median patient age was 2 years (range, 2 months-14 years). Mean serum free carnitine was 41.8 ± 19.2 μmol/L. In six of the 42 patients, serum free carnitine was <20 μmol/L (range, 4.0-18.7 μmol/L). C0 and C5-OH measured on MS/MS of DBS were 33.8 ± 20.2 nmol/mL and 0.48 ± 0.22 nmol/mL, respectively. There was a strong positive correlation (r = 0.89, P < 0.001) between serum free carnitine and C0 measured on the same day. In one patient on hydrolyzed formula, C5-OH was >1.00 nmol/L. Therapy-resistant eczema was improved by treatment with additional biotin and a non-hydrolyzed formula.
C0 and C5-OH, measured on MS/MS of DBS, were useful for screening carnitine and biotin deficiencies.
Abstract Parents of infants with autistic behaviors frequently face difficulties in childrearing owing to their infants' behavioral traits. This study aimed to clarify the characteristics of ...parent-infant interaction, parental depressive symptoms, and parenting stress in the context of infants' autistic behaviors. We employed a cross-sectional, case-control observational design with a case group of 52 parents and a control group of 56 parents. We measured parent-infant interaction using the Japanese version of the Nursing Child Assessment Teaching Scale, and parental depressive symptoms and parenting stress with the Japanese version of the Center for Epidemiologic Studies Depression Scale and the Japanese Parenting Stress Index Short Form, respectively. There was no significant difference between the two groups regarding parent-infant interaction. Mothers in the case group had significantly higher depressive symptoms than those in the control group (p < .05). Both fathers (p < .05) and mothers (p < .01) in the case group scored significantly higher than the control group on parenting stress. Thus, parents of infants with autistic behaviors have greater mental health problems right from infancy. We suggest that nurses should provide families with appropriate support to promote adaptive parent-infant interaction and prevent the aggravation of parental mental health problems irrespective of Autism Spectrum Disorder diagnoses.
Preoperative portal vein embolization (PVE) was performed in 84 patients before extensive liver resection for various diseases. By the criteria of liver volumetric determination, some patients were ...candidates for PVE, whereas others were not, even though the same surgical procedure, such as extended right lobectomy (ERL), was scheduled. PVE using gelatin sponge powder induced hypertrophy in the nonembolized lobe (0%‐171%; median, 30%) and proportional atrophy in the embolized lobe in 2 weeks without eliciting any major inflammatory or necrotic reaction, as evidenced histologically and by the minimal elevations in the serum aspartate transaminase (AST) and alanine transaminase (ALT) values. Alterations in the total bilirubin level and prothrombin time were also insignificant and transient, indicating that hepatocyte functions were not impaired by PVE. Not all patients who undergo PVE proceed with the scheduled hepatic resection procedure, so it is a great advantage that gelatin sponge causes minimal damage compared with other embolizing materials such as cyanoacrylate and absolute ethanol, which have been reported to induce an inflammatory reaction or histological alteration. Our multiple regression analysis showed that three factors, diabetes mellitus, a high total bilirubin level at the time of PVE, and being male, each reduced the extent of hypertrophy in the nonembolized lobe (r2 = .30). By contrast, cholestasis appeared to accelerate the process of atrophy in the embolized lobe (r2 = .16). In conclusion, PVE by gelatin sponge powder is a safe and effective preoperative maneuver that induces hypertrophy of the section of the liver that will remain after partial hepatectomy
To reveal the associated factors of quality of life (QoL) in children with inborn errors of metabolism (IEM), their siblings, and their primary caregivers and partners, we conducted an anonymous ...questionnaire survey in Japan. Descriptive, correlation, and multiple regression analyses were performed. Fifty-six children with IEM, 35 siblings, 143 primary caregivers, and 86 partners completed our questionnaires. There were significant positive correlations between higher QoL in children with IEM and lower disease influence (r = 0.46) and higher perceived emotional support (r = 0.67). We could not find any associated factor of siblings’ QoL. Lower parental distress, higher family empowerment, and higher household income contributed to higher QoL in primary caregivers (adjusted R
2 = 0.636). Higher household income, lower anxiety about childrearing, and higher satisfaction in the relationship with the child and entire family contributed to higher QoL of partners (adjusted R
2 = 0.398). We concluded that developing effective interventions to improve QoL is needed for the entire family in future outpatient settings.
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