Catastrophic antiphospholipid syndrome: first signs in the neonatal period

The term “catastrophic” antiphospholipid syndrome (CAPS) is used to define a subset of the antiphospholipid syndrome (APS) characterized by the clinical evidence of three or more organ involvement by thrombotic events in a short period of time and with laboratory confirmation of the presence of antiphospholipid antibodies. We describe a male infant first admitted at 17 days old for necrotizing enteritis complicated by cardiac and renal failure. Because of progressive renal function deterioration, a renal biopsy was performed at 8 months old, and histopathologic examination was compatible with renal venous thrombosis. Laboratory searching for vascular, prothrombotic, and metabolic disease was negative. Five months later, he developed two different episodes (20-day range) of ischemic stroke. Genetic test for thrombophilic conditions was positive for two different mutations, and repeatedly high titers of lupus anticoagulant, anticardiolipin, and anti-β2glicoprotein I antibodies were found. He was treated successfully with anticoagulants and showed a favorable clinical evolution. To the best of our knowledge, this is the youngest patient reported with probable CAPS. Although rare, APS/CAPS in the neonatal period or in the first year of life must be suspected in infants presenting with thrombotic phenomena. The present case illustrates the importance of an early diagnosis and treatment to enhance possibilities of survival.     

Long-term follow-up of a girl with Maroteaux-Lamy syndrome after bone marrow transplantation

Background  Mucopolysaccharidosis type VI (MPS VI or Maroteaux-Lamy syndrome) is a rare autosomal recessive genetic disorder. We treated a 10-year-old girl with Maroteaux-Lamy syndrome successfully with bone marrow transplantation (BMT). Methods  The patient had reconstitution with bone marrow from her HLA-matched brother. One month after BMT, arylsulfatase activity of the recipient’s leukocytes became normal. No graft-versushost disease (GVHD) was observed. Arylsulfatase B activity was maintained and the urinary excretion of glycosaminoglycans (GAGs) became normal. Results  The clinical response of the patient was slow but persistent during 12 years after BMT. Improved motor function included walking alone for a long distance without aid, riding a bicycle, taking a bath by herself, etc. Besides, few infections occurred. Exertional dyspnea, severe snoring, and vertigo were much improved. Conclusions  Early intervention is recommended for BMT. Allogeneic BMT may provide a better life quality as illustrated in the present case.     

Congenital ureteric stenosis: a study of 17 children

Aim  To review cases of congenital ureteric stenosis treated in the period between 1999 and 2007. We propose to analyze the type of presentation, management and results. Material and methods  We report 17 children aged 20 days to 8 years with obstructive uropathy due to congenital stenosis of the ureter at one or more levels. This condition could be mistaken for the more common pelviureteric junction obstruction (PUJO) or primary megaureter, but it is a distinct and more serious anomaly. 13 of the 17 children had one or more associated anomalies, the most significant of which was a contralateral multicystic dysplastic kidney. Other associated anomalies included PUJO, megacalyx, vesicoureteric reflux, urogenital sinus, duplicate vagina, anorectal malformation and agenesis of the bladder. 16 children were symptomatic at presentation, with uremia (serum creatinine >1 mg/dl) in 5, while 1 was diagnosed antenatally. The correct preoperative diagnosis was made in only three children. Reconstruction included ureteroureteral anastomosis, ureteric reimplantation or ureteral substitution. Results  There is follow up for 15 of the 17 patients. Length of follow up ranges from 1 to 7 years (average 2.7 years). There was satisfactory urinary drainage established in all 17 cases and uremia has resolved 3 of the 5 children. The children with solitary functioning kidney are at risk of uremia in later life. Conclusion  Congenital ureteric stenosis is a rare condition, but distinct anomaly with possible grave consequence and has been distinguished from other causes of congenital ureteric obstruction.     

Long-term outcomes of surgery for malignant sacrococcygeal teratoma: 20-year experience of a regional UK centre

Background  The timing of surgery for malignant sacrococcygeal teratoma is controversial. The long-term outcomes and complications of surgery for this rare tumour are presented. Methods  All cases of malignant sacrococcygeal teratoma in the 20-year period 1987–2006 were identified and the case notes retrieved. The age at diagnosis, investigations, presentation, type of surgery, early complications, recurrence rates, long-term complications and outcomes were recorded. Results  Twelve patients (three males, nine females) were identified. Mean age at presentation was 20.8 months (range: 12–39 months). All had the Carboplatin–Etoposide–Bleomycin chemotherapeutic protocol. The average time of follow-up was 10.6 years (range: 1–17 years). Ten patients had excision of their tumours following chemotherapy, whilst two patients had excision prior to chemotherapy. Two patients had recurrence of their tumours. There was one death (8%), which was due to disseminated metastasis. The other 11 children were all well at the last follow-up. Conclusion  Surgery for malignant sacrococcygeal teratoma is safe and has a low complication rate. The long-term outcomes are favourable with minimal side effects.     

Long-term outcome of asymptomatic patients with congenital cystic adenomatoid malformation

Purpose  Congenital cystic adenomatoid malformation (CCAM) represents a rare congenital anomaly of the lung. It remains controversial whether patients with asymptomatic lesions warrant early surgical intervention. Our aim was to review the outcome of asymptomatic CCAM patients at a paediatric tertiary centre. Methods  The medical case notes of all children with CCAM presenting to our institution between 1986 and 2007 were reviewed. Data on pre- and post-natal investigations, clinical presentation, lesion site, type of surgical procedure, timing, and outcomes of surgery were reviewed. Results  A total of 35 patients were diagnosed with CCAM during the 21-year study period (1986–2007). Sixty percent (n = 21) were asymptomatic at birth including eight patients with prenatal ultrasound scan confirming CCAM. In this group, 18 patients (86%) subsequently developed symptoms (median age 2 years, range 1 month–13 years) and required surgery. Symptoms included pneumonia with or without infected CCAM (43%), respiratory distress (14%) and spontaneous pneumothorax (14%). Eight patients underwent multiple hospital presentations with complications related to CCAM. Of the 21 initially asymptomatic patients, 17 (81%) underwent surgical resection. Only one of these patients was completely asymptomatic prior to surgery. There were eight post-operative complications and no mortality. One patient underwent a second thoracotomy for residual CCAM. The median length of hospital stay was 9 days (range 3–32 days). Conclusion  This study suggests patients who present with asymptomatic CCAM will subsequently become symptomatic. Early surgical referral and intervention may be beneficial to avoid the development of complications.     

The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia,short limb-abnormal calcification type

A 1-month-old boy with shortness of extremities on prenatal US was referred to our department with a provisional diagnosis of achondroplasia. His height was normal but he had short extremities and platyspondyly, premature carpal epiphyses on both hands, and short tubular bones with irregular metaphyses on radiographs. Re-evaluation of the patient at the age of 1 year revealed very short height and premature calcification of the costal cartilages and epiphyses. Spondylometaepiphyseal dysplasia (SMED), short limb-abnormal calcification type was diagnosed. This condition is a very rare autosomal recessively inherited disorder, and most of the patients die in early childhood due to neurological involvement. At the age of 2 years and 5 months, a CT scan showed narrowing of the cervical spinal canal. One month later he died suddenly because of spinal cord injury. In conclusion early diagnosis is very important because the recurrence risk is high and patients may die due to early neurological complications. The time of onset of abnormal calcifications, a diagnostic finding of the disease, is at the age of around 1 year in most patients. When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered.     

Xanthogranulomatous Pyelonephritis in a male child with renal vein thrombus extending into the inferior vena cava: a Case Report

Background  

We present a case of Xanthogranulomatous pyelonephritis (XGPN) in a male child with renal vein thrombus extending into the inferior vena cava. This is a rare presentation. XGPN is a rare type of renal infection characterised by granulomatous inflammation with giant cells and foamy histiocytes. The peak incidence is in the sixth to seventh decade with a female predominance. XGPN is rare in children.     

Autoimmune polyglandular syndrome Type 3 and growth hormone deficiency

Quintos JB, Grover M, Boney CM, Salas M. Autoimmune polyglandular syndrome type 3 and growth hormone deficiency. The simultaneous occurrence of prepubertal Graves' disease, type 1 Diabetes Mellitus (DM), and Growth hormone deficiency (GHD) is uncommon. GHD has been reported in Autoimmune Polyglandular Syndrome (APS) Type 1 and Type 2 but not in APS Type 3. We report a 3‐yr‐old boy who presented simultaneously with type 1 DM and Graves' disease. After he developed urticarial rash to Propylthiouracil and Methimazole with persistent thyrotoxicosis, he received 8 millicuries of ¹³¹I at 5 yr of age. We diagnosed GHD at age 8 yr 8 months because of growth deceleration (from 95 to 25%) and abnormal growth rate (3 cm/yr) despite euthyroidism, fair glycemic control, and normal weight gain. Both insulin‐like growth factor (IGF) 1 (90 ng/mL; normal 113–261 ng/mL) and IGFBP3 (1.3 mcg/mL; normal 2.1–4.2 mcg/mL) levels were low and peak growth hormone level measured by RIA was 5.2 ng/mL after L‐Dopa and insulin tolerance test. The rest of his pituitary functions and magnetic resonance imaging of the pituitary gland were normal. Growth hormone treatment (0.3 mg/kg/wk) was administered at 8 yr 9 months until near final adult height (FAH). Near FAH (172 cm) was close to midparental target height of 180 cm. GHD may be a component of all APS even though it is rare. Growth in treated children with Graves' disease should be followed closely as catch down growth below genetic height potential may be a harbinger of underlying GHD.     

Cardiovascular Complications Associated with Chronic Active Epstein–Barr Virus Infection

This study aimed to assess the outcome of cardiovascular diseases for patients with chronic active Epstein–Barr virus infection (CAEBV). The study enrolled 15 patients (7 boys and 8 girls) who fulfilled the diagnostic criteria for CAEBV, including 10 patients with T-cell type and 3 patients with natural killer (NK)-cell type. The median age at the CAEBV onset was 6.3 years (range, 1.2–17.8 years). Regular cardiologic studies were performed during the median follow-up period of 8 years (range, 2–20 years). Nine patients (60%) had cardiac diseases including coronary artery lesion (CAL) (n = 4, 44%), decreased left ventricular ejection fraction and pericardial effusion in (n = 3, 33%), complete atrioventricular block (n = 1), and sudden arrest (n = 1). The frequency of fever (78%, p = 0.04) or cytopenias (100%, p = 0.01), as the major symptom among patients with cardiac complications, was higher than among those without complications. The median time from disease onset to detection of CAL was 3.4 years (range, 1.8–8.6 years). The mean z-score increased to 3.98. Seven patients (78%) with cardiac complications died of disease progression, hematopoietic stem cell transplantation–related events, or both. In two patients, CAL regressed after allogeneic cord blood transplantation. Among CAEBV patients, CAL was the most common cardiac complication and could not be controlled without the eradication of EBV-infected T- and NK-cells.     

Breastfeeding duration in infancy and adult risks of type 2 diabetes in a high‐income country

Observed associations between breastfeeding and reduced risk of type 2 diabetes in adulthood may be confounded. We examined if the duration of breastfeeding in infancy was associated with the risk of type 2 diabetes in adulthood after adjustment for a range of prenatal and postnatal risk factors. We prospectively followed 6,044 individuals from the Copenhagen Perinatal Cohort born 1959–1961. Duration of any breastfeeding (≤0.5, >0.5–1, >1–2, >2–4, >4 months) was assessed at the infant's 1‐year health examination. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for type 2 diabetes (at age ≥30 years, 237 persons) by breastfeeding duration without and with adjustment for parental social status and education, maternal pre‐pregnancy body mass index (BMI), maternal diabetes and smoking during pregnancy, gestational weight gain, parity, preterm birth, birth weight, sex, and BMI at ages 7 and 41–43 years. In the unadjusted analysis, compared with infants breastfed for ≤0.5 month, those breastfed for >4 months had a 51% reduced risk of type 2 diabetes (HR = 0.49; 95% CI [0.32, 0.75]). After the stepwise adjustment for putative early life confounders, this was attenuated to a nonsignificant 31% reduced risk (HR = 0.69; 95% CI [0.44, 1.07]). Adjustment for childhood and adulthood BMI minimally changed the results. We found that the inverse association between the duration of breastfeeding and risk of type 2 diabetes in adulthood is considerably weakened and no longer significant after adjustment for prenatal and postnatal factors in the infant and mother.     

Spondyloepimetaphyseal dysplasia,short limb-abnormal calcifications type: progressive radiological findings from fetal age to adolescence

Background  

Spondyloepimetaphyseal dysplasia, short limb-abnormal calcifications type (SEMD, SL-AC) is a rare autosomal recessive condition with a grave prognosis.     

Long-term survival with cloacal dysgenesis sequence

Cloacal dysgenesis sequence (CDS) is a rare and lethal malformation. We report such a case of long-term survival, currently to 12 years of age. In the fetal period, she received a timely placement of vesico-amniotic shunt for a megabladder due to a severe urethral obstruction. Postnatally, cystostomy and colostomy were created because of no perineal opening of urethra, vagina, and anus. Anorectoplasty, construction of efferent conduit, and colostomy closure were performed at 4 years of age. Ileovaginoplasty and ileovesicostomy which was a Mitrofanoff-type of conduit, and labioplasty were performed at the age of 11 years. To the best of our knowledge, only five survivors with CDS over 1 year of age have been reported.     

Combined liver‐kidney transplantation for primary hyperoxaluria type I in children: Single Center Experience

Primary hyperoxalurias are rare inborn errors of metabolism with deficiency of hepatic enzymes that lead to excessive urinary oxalate excretion and overproduction of oxalate which is deposited in various organs. Hyperoxaluria results in serious morbid‐ity, end stage kidney disease (ESKD), and mortality if left untreated. Combined liver kidney transplantation (CLKT) is recognized as a management of ESKD for children with hyperoxaluria type 1 (PH1). This study aimed to report outcome of CLKT in a pediatric cohort of PH1 patients, through retrospective analysis of data of 8 children (2 girls and 6 boys) who presented by PH1 to Wadi El Nil Pediatric Living Related Liver Transplant Unit during 2001‐2017. Mean age at transplant was 8.2 ± 4 years. Only three of the children underwent confirmatory genotyping. Three patients died prior to surgery on waiting list. The first attempt at CLKT was consecutive, and despite initial successful liver transplant, the girl died of biliary peritonitis prior to scheduled renal transplant. Of the four who underwent simultaneous CLKT, only two survived and are well, one with insignificant complications, and other suffered from abdominal Burkitt lymphoma managed by excision and resection anastomosis, four cycles of rituximab, cyclophosphamide, vincristine, and prednisone. The other two died, one due to uncontrollable bleeding within 36 hours of procedure, while the other died awaiting renal transplant after loss of renal graft to recurrent renal oxalosis 6 months post‐transplant. PH1 with ESKD is a rare disease; simultaneous CLKT offers good quality of life for afflicted children. Graft shortage and renal graft loss to oxalosis challenge the outcome.     

Fetal MR imaging of posterior intracranial dural sinus thrombosis: a report of three cases with variable outcomes

Background  

Thrombosis of fetal intracranial dural sinuses is a rare entity. A specific type of midline dural sinus thrombosis (DST) at the torcular Herophili with extension into the superior sagittal sinus (SSS) was initially seen on fetal US and was referred to fetal MRI for definite diagnosis and better delineation.     

Predicting chance of liver transplantation for pediatric wait‐list candidates

Information about wait‐list time has been reported as one of the single most frequently asked questions by individuals awaiting a transplant but data regarding wait‐list time have not been processed in a useful way for pediatric candidates. To predict chance of receiving a DDLT, we identified 6471 pediatric (<18 years), non status‐1A, liver‐only transplant candidates between 2006 and 2017 from the SRTR. Cox regression with shared frailty for DSA level effect was used to model the association of blood type, weight, allocation PELD and MELD, and DSA with chance of DDLT. Jackknife technique was used for validation. Median (interquartile range) wait‐list time was 100 (34‐309) days. Non‐O Blood type, higher PELD/MELD score at listing, and DSA were associated with increased chance of DDLT, while age 1‐5 years and 10‐18 years was associated with lower chance of DDLT (P < 0.001 for all variables). Our model accurately predicted chance of transplant (C‐statistic = 0.68) and was able to predict DDLT at specific follow‐up times (eg, 3 months). This model can serve as the basis for an online tool that would provide useful information for pediatric wait‐list candidates.     

Anal canal duplication: case reviews and summary of the world literature

Anal canal duplication (ACD) is a rare entity that is difficult to recognize. After the presentation of two patients, a review of the literature found 45 reported patients with ACD. This article presents the largest collection of known patients ACD in the literature. Of the 47 patients, 43 were female. The mean age at presentation was 28 months (range 0–24 years). The majority of the duplications were discovered incidentally (n = 21). Several presented with infectious complications such as epidural abscess with sepsis. Forty-two patients manifested an opening in the midline posterior to the native anus. Eighteen patients had associated anomalies, the majority of which were midline. Thirty-five of the patients underwent successful resection with rare complications. ACDs characteristically appear in females as incidental findings of an extra perineal orifice. They are frequently associated with additional congenital anomalies. Generally, ACDs are resectable with excellent outcomes.     

Evaluation of bowel function in healthy children: untreated constipation is common

Aim

We evaluated bowel function in healthy children with regard to gender and age.

Methods

The study was carried out in 2016 at a tertiary children's hospital. Healthy children aged 3.5 years to 15 years who were admitted to the hospital, siblings to patients or offspring of staff members were included. Validated self‐report questionnaires and internally developed questions regarding obstructive outlet‐ and gas‐related symptoms were used.

Results

A total of 310 participants (50% girls) were included, which corresponded to a 94% answer frequency. Respondents were divided into a younger age group (3.5 years to seven years), consisting of 135 children, and an older age group (eight years to 15 years), consisting of 175 children. Younger children reported more foul odours than older children (50% vs. 29%, p = 0.001) and more obstructive symptoms (21% vs. 10%, p = 0.01). There was no difference between the age groups regarding constipation (19% vs 16%, NS). Overall, 55% of those with constipation had no treatment for the condition, although they reported abdominal pain (51%) and problems with foul odours (57%).

Conclusion

Healthy children frequently reported constipation, abdominal pain and gas‐related problems, but treatment was rare. Overall, bowel function seemed to improve during childhood, although constipation remained largely untreated.     

Transient elastography assessment of liver allograft fibrosis in pediatric transplant recipients

TE measures liver stiffness to assess fibrosis. Its use in post‐transplant patients was reported in few small pediatric studies. We evaluated TE ability to predict liver graft fibrosis in a large cohort while comparing it to the performance of APRI and FIB‐4. We also investigated the effect of graft type on LSMs. Patients at Boston Children's Hospital who underwent LT and LSM ≤ 1 year from biopsy (2007‐2018) were eligible. Ninety‐four patients (45%M) aged 1‐21 years (89% < 18 years; 13% < 2 years) were eligible. Median time between transplant/biopsy and LSM was 5.1 years and 52 days, respectively. Thirty‐nine percent received whole‐liver grafts, 54% TV grafts, and 6% as part of MV. At LSM, median ALT was 25 [IQR 16‐33] IU/L. Twenty‐one percent had METAVIR ≥ F2. LSM was statistically higher among those with significant fibrosis (METAVIR ≥ F2) compared to those with METAVIR F0/F1 (median [IQR] 7.5 [4.6, 13.6] vs 5.1 [4.0, 6.4] kPa, respectively) (P = .005 by Wilcoxon rank‐sum test). APRI and FIB‐4 distributions were not different across METAVIR stages. The AUROC for LSM was 0.71 (95% CI 0.56‐0.85) with an optimal cut‐point of 6.5 kPa. Graft type had no influence on the AUROC for LSM. TE is useful for assessing significant graft fibrosis in children and young adult LT recipients and performs better than APRI and FIB‐4. TV grafts demonstrate similar correlation with histology as whole‐liver grafts.     

Delayed menarche in young German women with type 1 diabetes mellitus: recent results from the DPV diabetes documentation and quality management system

Background  Findings have been inconsistent regarding the effect of T1DM (type 1 diabetes) on age at menarche. Objective  The purpose was to investigate in young German women with T1DM menarcheal age and factors potentially affecting menarche, including glycemic control, BMI (body mass index), relative T1DM duration (proportion of life with diabetes), insulin dose, and insulin therapy intensity. Initiated in 1990, the DPV program is an ongoing, prospective long-term longitudinal follow-up study to benchmark the quality of care provided to pediatric and, more recently, adult diabetes patients. Two hundered two German diabetes centers participated in nationwide data collection. Based on ethnicity and the availability of menarche and T1DM onset data as the main inclusion criteria, 643 young German women were selected from 11,629 female T1DM patients aged <20 years, recruited by referral, clinic or hospital ascertainment, or self report. Mean age at menarche (±SD) was 13.22 ± 1.31 years, representing a delay of 0.52 years (p < 0.001) relative to the general population. Significant delay (p < 0.05) was also found for relative T1DM duration, BMI SD score, insulin dose, and HbA1c level, with a 1% increase in HbA1c resulting in a delay in menarche by 0.07 years. Conclusions  Age at menarche is delayed in type 1 diabetes mellitus. The delay increases with relative T1DM duration and poor quality of glycemic control.