Progressive pseudorheumatoid dysplasia misdiagnosed as juvenile idiopathic arthritis: a case report.

BACKGROUND: Progressive pseudorheumatoid dysplasia is a rare, autosomal recessively inherited, noninflammatory musculoskeletal disorder caused by mutations occurring in the WNT1-inducible signaling pathway protein 3 gene. Joint cartilage is the primary site of involvement, leading to arthralgia, joint stiffness, contractures, enlargement of the epiphyses and metaphysis of the hand joints, spinal abnormalities, short stature, early osteoarthritis, and osteoporosis. Juvenile idiopathic arthritis is the most common chronic rheumatic disease in childhood and has unknown etiology. Clinical features of progressive pseudorheumatoid dysplasia resemble those of juvenile idiopathic arthritis. Patients with progressive pseudorheumatoid dysplasia are usually misdiagnosed as having juvenile idiopathic arthritis. CASE PRESENTATION: A 13-year-old Yemeni female presented to the rheumatology clinic with a history of joint pains, bone pains, and bone deformity for 7 years. Weight and height were below the third percentiles. There was no tender swelling of metacarpophalangeal and interphalangeal joints, and she presented with scoliosis. Radiographs of the hands revealed the widening of the epiphyses. Progressive pseudorheumatoid dysplasia was suspected, and genetic testing for WNT1-inducible signaling pathway protein 1, 2, and 3 was requested with these findings. A homozygous, likely pathogenic variant was identified in the WNT1-inducible signaling pathway protein 3 gene, which confirmed our diagnosis. CONCLUSION: Progressive pseudorheumatoid dysplasia is a rare form of spondyloepimetaphyseal dysplasia and is clinically misdiagnosed as juvenile idiopathic arthritis. It is crucial to consider progressive pseudorheumatoid dysplasia, especially in patients with standard inflammatory markers who are being followed up for juvenile idiopathic arthritis and not improving with antirheumatic intervention.

Pseudotumor cerebri in patient on leuprolide acetate for central precocious puberty.

BACKGROUND: Gonadotropin releasing hormone agonists (GnRHa) are well established as a standard of care for the treatment of central precocious puberty (CPP) worldwide. While numerous delivery systems and routes of administration exist, depot intramuscular injections or sustained-release preparations have been most widely used. Leuprolide acetate is well tolerated among children though some can develop some complications. CASE PRESENTATION: We present a case report of a 6.5 year old girl with central precocious puberty who developed signs of pseudotumor cerebri after 2 doses of leuprolide acetate 3.75 mg given monthly. Systemic exam and other tests to look for the cause did not yield anything. However, fundoscopy showed marked papilloedema with blurred disc margins. After six weeks' treatment with acetazolamide and withdrawal of the GRNHa the papilloedema resolved. CONCLUSIONS: If a patient presents with complaints such as headache, nausea, vomiting, and double vision in pediatric patients treated with GnRH analogue one should highly consider the presence of pseudotumor cerebri and fundus examination be performed.

Outcomes of Children and Adolescents Admitted with Diabetic Ketoacidosis at Kenyatta National Hospital (KNH), Kenya.

BACKGROUND: Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication that mainly occurs in patients with type 1 diabetes mellitus and is the foremost cause of death in these children. Overall mortality in children with DKA varies from 3.4% to 13.4% in developing countries. There is a need to understand outcomes among children with DKA in sub-Saharan African countries. OBJECTIVE: To determine the death rate and clinical outcomes of children and adolescents aged 0-18 years managed for DKA at Kenyatta National Hospital (KNH). Study Methods. This was a retrospective study carried out among children aged 0-18 years admitted with DKA at KNH between February 2013 and February 2018. The study site was the central records department at KNH. The inclusion criteria were children aged 0-18 years admitted with a diagnosis of DKA based on the ISPAD guidelines biochemical criteria. RESULTS: Out of the 159 files reviewed, the median age of children was 13 years (IQR 10-15). 41.1% of patients had severe DKA while 35.7% had moderate DKA. We reported a mortality of 6.9% while 93.1% of children recovered and were discharged home. The median duration of hospital stay was 8 days. High risk of mortality was reported among children who had high serum creatinine (OR 5.8 (95% CI 1.6-21.2)), decreased urine output (OR 9.0 (95% CI 2.2-37.3)), and altered level of consciousness (OR 5.2 (95% CI 1.1-25.1)). CONCLUSION: DKA-associated mortality in our study was low at 6.9%. High serum creatinine, decreased urine output, and altered level of consciousness were associated with a significantly higher risk of mortality.

Continuous glucose monitoring assessment of metabolic control in east African children and young adults with type 1 diabetes: A pilot and feasibility study.

BACKGROUND: For individuals with type 1 diabetes (T1D) in East Africa and other low-income regions, the last decade has seen substantial gains in access to insulin and trained healthcare providers, yet metabolic control remains poor. METHODS: The objective was to determine the feasibility of continuous glucose monitoring (CGM) and to gather baseline metabolic data for future power analysis in Ugandan and Kenyan youth with T1D using a Freestyle Libre Pro blinded CGM. RESULTS: Of 78 participants recruited, four sensors fell off and six patients did not return, leaving 68 evaluable subjects. Average age was 16 ± 5 (range 4-26) years, 43% female. Average diabetes duration was 7 ± 5 years, insulin dose 0.9 ± 0.3 U/kg/d, and number of fingerstick glucose levels per day 2.1 ± 1.1. All were on human insulin. Point-of-care HbA1c was 10.9 ± 2.7% (96 ± 30 mmol/mol). Mean number of sensor days was 13 ± 3; >90% wore the sensor for ≥10 days. Mean glucose was 231 ± 86 mg/dL (12.8 ± 4.8 mmol/L). Only 30 ± 19% of time was spent in the target range (70-180 mg/dL; 3.9-10 mmol/L), and 7 ± 8% of time was spent in hypoglycaemia (glucose <55 mg/dL, 3.0 mmol/L). Hypoglycaemia occurred in 81% of participants, averaging five events/wk with an average duration of 140 ± 79 minutes/event. CONCLUSIONS: Despite significant diabetes care improvements, East African youth with T1D have poor metabolic control with chronic hyper- and hypoglycaemia, placing them at high risk for serious acute and chronic complications. This study demonstrates the feasibility of CGM use in this population and provides baseline metabolic data that will be used to inform a future intervention study.

Etiology and Clinical Presentation of Disorders of Sex Development in Kenyan Children and Adolescents.

OBJECTIVE: The purpose of this study was to describe baseline data on etiological, clinical, laboratory, and management strategies in Kenyan children and adolescents with Disorders of Sex Development (DSD). METHODS: This retrospective study included patients diagnosed with DSD who presented at ages 0-19 years from January 2008 to December 2015 at the Kenyatta National (KNH) and Gertrude's Children's (GCH) Hospitals. After conducting a search in the data registry, a structured data collection sheet was used for collection of demographic and clinical data. Data analysis involved description of the frequency of occurrence of various variables, such as etiologic diagnoses and patient characteristics. RESULTS: Data from the records of 71 children and adolescents were reviewed at KNH (n = 57, 80.3%) and GCH (n = 14, 19.7%). The mean age at the time of diagnosis was 2.7 years with a median of 3 months. Thirty-nine (54.9%) children had karyotype testing done. The median age (IQR) of children with reported karyotypes and those without was 3.3 years (1.3-8.9) and 8.3 years (3.6-12.1), respectively (p=0.021). Based on karyotype analysis, 19 (48.7%) of karyotyped children had 46,XY DSD and 18 (46.2%) had 46,XX DSD. There were two (5.1%) children with sex chromosome DSD. Among the 71 patients, the most common presumed causes of DSD were ovotesticular DSD (14.1%) and CAH (11.3%). Majority (95.7%) of the patients presented with symptoms of DSD at birth. The most common presenting symptom was ambiguous genitalia, which was present in 66 (93.0%) patients either in isolation or in association with other symptoms. An ambiguous genitalia was initially observed by the patient's mother in 51.6% of 62 cases despite the high rate (84.7%) of delivery in hospital. Seventeen (23.9%) of the cases had a gender reassignment at final diagnosis. A psychologist/psychiatrist or counselor was involved in the management of 23.9% of the patients. CONCLUSION: The commonest presumed cause of DSD was ovotesticular DSD in contrast to western studies, which found CAH to be more common. Investigation of DSD cases is expensive and needs to be supported. We would have liked to do molecular genetic analysis outside the country but financial challenges made it impossible. A network for detailed diagnostics in resource-limited countries would be highly desirable. There is a need to train health care workers and medical students for early diagnosis. Psychological evaluation should be carried out for all patients at diagnosis and support given for families.

Audit of Antibiotic Prescribing Practices for Neonatal Sepsis and Measurement of Outcome in New Born Unit at Kenyatta National Hospital.

BACKGROUND: Neonatal sepsis is a leading cause of morbidity and mortality globally. A high index of suspicion is required since features of sepsis are nonspecific. Auditing of antibiotic use is necessary to reduce misuse and minimise development of antibiotic resistance. OBJECTIVES: To assess the antibiotic prescribing practices in NBU at KNH against recommended Kenyan guidelines for neonatal sepsis. In addition, outcome within 7 days was described. METHODS: This was a prospective audit of 320 neonates over a 2-month period at NBU of KNH. Data were collected using a structured questionnaire, stored in MS-EXCEL, and analysed using STATA. RESULTS: Documentation of perinatal risk factors and clinical features at admission and at the time of change of antibiotics was very poor. The rate of investigations to confirm infection was very low. Blood cultures were done only in 13 (4%) neonates on admission, while complete blood count and C reactive protein were done in 224 (70%) and 198 (62%), respectively. Appropriate antibiotics as per the Kenyan guidelines were prescribed in 313 (97.8%) of neonates on admission. However, these were not stopped at 48-72 hours for the 148 (53.62%) who had improved. Overall mortality was high in neonates at 80 (25%). Majority (55%) died within 48 hours. Mortality was high among preterm neonates; 70 (43.8%) died out of 160. CONCLUSION: Overall documentation and investigations to confirm infection was poor. The continuation of antibiotics was inappropriate. Overall mortality was high especially in the first 48 hours of admission. To improve documentation, availability of a checklist on admission is recommended.

Serum alkaline phosphatase levels in healthy children and evaluation of alkaline phosphatase z-scores in different types of rickets.

OBJECTIVE: Serum alkaline phosphatase (ALP) levels show great variation with age and sex in children and adolescents. Additionally, different buffers used even in the same method cause variable results. This detail is not usually taken into account in the evaluation. We aimed to study pediatric age- and sex-specific reference ranges for ALP by colorimetric assay using p-nitrophenyl phosphate as substrate and diethanolamine as buffer and also to compare the ALP levels in patients with different types of rickets. METHODS: 1741 healthy children and adolescents (904 girls) were included in the study for normative data. 77 different ALP measurements from 38 nutritional rickets (NR), 7 vitamin D-dependent rickets (VDDR) and 8 hypophosphatemic rickets (HR) patients were included. RESULTS: Reference values for ALP were constructed. ALP levels demonstrated a tetraphasic course with two peaks at infancy and puberty. There was no difference in ALP levels between boys and girls until puberty. However, higher ALP levels were noted at 10-11 years in girls (p=0.02) and at 12-13, 14-15, 16-17 years in boys (p<0.001). ALP levels start to decline after age 12 and 14 in girls and boys, respectively. Serum ALP levels were highest in the VDDR group and lowest in the HR group (median z-score values in HR, VDDR and NR were 3.6, 10.4 and 6.5, respectively; p<0.001). Similarly, plasma parathormone(PTH) levels ranged from highest to lowest in the VDDR, NR and HR groups (median values: 525, 237 and 98 pg/mL, respectively; p<0.001). CONCLUSIONS: This normative data will provide a basis for better evaluation of ALP levels determined by the described method. Furthermore, use of z-scores gives a more precise assessment of changes in ALP levels in rickets and other bone disorders.

Comparison of capillary blood ketone measurement by electrochemical method and urinary ketone in treatment of diabetic ketosis and ketoacidosis in children.

We aimed to compare the recent practical method of capillary beta-hydroxy butyrate (betaOHB) measurement with the widely used urinary ketone measurement in monitoring metabolic status of the patient during treatment of diabetic ketoacidosis (DKA) and diabetic ketosis (DK). Patients with DKA and DK admitted to the hospital were followed with simultaneous measurements of capillary betaOHB by electrochemical method (Medisense Optium, Abbott), and urinary ketone by semi-quantitative method. Blood gases were measured in 2-4 h intervals. Fourteen patients with DKA/DK (7 males and 7 females, age: 9.2 +/- 4.2 years) were included with 50 simultaneous measurements of capillary and urinary ketone. No correlation was detected between urinary ketone and blood pH (P = 0.06) and HCO3 (P = 0.79), whereas a significant negative correlation was found between capillary betaOHB and blood pH (r = -0.41, P < 0.05) and HCO3 (r = -0.35, P < 0.05). Capillary betaOHB and urinary ketone levels did not correlate at the beginning and 3.3 +/- 1.4 h after treatment, but did correlate in the third samples taken 7.8 +/- 2.0 h after treatment (r = 0.8, P < 0.05). Capillary betaOHB levels show good correlation with the degree of acidosis (pH and HCO3). Capillary betaOHB measurement is more sensitive than urinary ketone measurement in reflecting the patient's metabolic status and improvement during treatment.

Serum IGF-I and IGFBP-3 levels of Turkish children during childhood and adolescence: establishment of reference ranges with emphasis on puberty.

AIMS/METHODS: We established age- and sex-related reference ranges for serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in 807 healthy Turkish children (428 boys, 379 girls), and constructed a model for calculation of standard deviation scores of IGF-I and IGFBP-3 according to age, sex and pubertal stage. RESULTS: Serum IGF-I and IGFBP-3 concentrations tended to be higher in girls compared to boys of the same ages, but the differences were statistically significant only in pubertal ages (9-14 years) for IGF-I and only in prepubertal ages for IGFBP-3 (6-8 years) (p < 0.05). Peak IGF-I concentrations were observed earlier in girls than boys (14 vs. 15 years, Tanner stage IV vs. V) starting to decline thereafter. IGFBP-3 levels peaked at age 13 and at Tanner stage IV in both sexes with a subsequent fall. Serum levels of IGF-I and IGFBP-3 increased steadily with age in the prepubertal stage followed by a rapid increase in IGF-I in the early pubertal stages. A relatively steeper increase in IGF-I but not in IGFBP-3 levels was observed at age 10-11 years in girls and at 12-13 years in boys which preceded the reported age of pubertal growth spurt. At late pubertal stages, both IGF-I and IGFBP-3 either did not change or decreased by increasing age. Interrelationships between growth factors and anthropometric measurements have been described, and the physiologic consequences of these have been discussed in detail. CONCLUSIONS: Differences in the pattern of IGF-I and IGFBP-3 in the present paper and those reported in other studies emphasize the importance of locally established reference ranges. Establishment of this reference data and a standard deviation score prediction model based on age, sex and puberty will enhance the diagnostic power and utility of IGF-I and IGFBP-3 in evaluating growth disorders in our population.