Nutritional status of children with primary immunodeficiency: A single center experience.

BACKGROUND: Nutritional status in primary immunodeficiencies (PID) is a major factor influencing immune defense. We aimed to evaluate the nutritional status of patients with PID. METHODS: Demographic findings and anthropometric measurements of 104 patients were recorded for this cross-sectional study. RESULTS: Combined immunodeficiencies (n = 49), predominantly antibody deficiencies (n = 28) and phagocytic system disorders (n = 17), were the major disease groups. In total, 44 (42.3%) patients had at least one anthropometric measurement below -2 standard deviations. Chronic, acute, and mixed-type malnutrition were detected in 18.3%, 16.3%, and 7.7% of the patients, respectively. No significant difference was detected among groups regarding anthropometric measurements however higher malnutrition rates were observed in 'combined immune deficiency less profound than severe combined immuno deficiency' (52%), chronic granulomatous disease (66.6%), and X-linked agammaglobulinemia (50%) patients. Severe malnutrition was present in 22 (21.2%) of the patients, although it was not significant. It was more common in the phagocytic system disorder group. All patients in the severe combined immunodeficiency group had undergone hematopoietic stem cell transplantation and 50% of them had malnutrition. There was also no significant difference regarding age, sex, anthropometric indexes (Weight for age, lenght/height for age body mass index Z-scores), malnutrition types, and prevalence of malnutrition among three major disease groups. Only the hospitalization history inversely related to body mass index and weight for age Z-scores (P < 0.0001). In patients with malnutrition, daily caloric intake was at least 20% or more below the requirement. CONCLUSIONS: Regardless of the type of immunodeficiency, nutritional status was poor in PID and hospitalization is the most important determinant of nutritional status. Even after hematopoietic stem cell transplantation, nutritional support should be continued.

Cystinosis beyond kidneys: gastrointestinal system and muscle involvement.

BACKGROUND: Cystinosis is a multisystemic disease resulting from cystine accumulation primarily in kidney and many other tissues. We intended to study the evolution of less commonly seen extrarenal complications of cystinosis in a group of patients who have periods without cysteamine treatment. METHODS: Gastrointestinal and muscular complications of cystinosis were studied in a group of 21 patients. RESULTS: Twenty one patients were included in the study. Among them, 14 were homozygous and 3 were compound heterozygous for CTNS mutations. The median age of diagnosis was 15 months (range; 5 months-14 years) and the mean age at last visit was 11.3 ± 6.5 years. Nine patients (42%) had end stage renal disease at a mean age of 10.6 years (6.5-17 years). Abdominal ultrasonography and portal vein doppler ultrasonography were performed in19 patients, 14 of them (74%) had hepatomegaly, 10 patients (53%) had granular pattern or heterogeneity of liver. Only one patient had high transaminase levels and liver biopsy showed cystine crystals in the liver. Eleven patients (58%) had borderline or increased portal vein minimum and maximum flow velocities. One patient had CK level of 9024 U/L and electromyographic study showed active myopathic involvement. Two patients were found to have gastroesaphageal reflux only and 4 patients were found to have esophageal remnants in addition to reflux. CONCLUSIONS: In addition to renal functions, extrarenal organs may be affected from cystine accumulation even in childhood, especially in patients who are incompliant to treatment, resulting in complications such as swallowing difficulty, hepatomegaly and portal hypertension.

Clinical and histopathological features of immunoglobulin G4-associated autoimmune hepatitis in children.

BACKGROUND AND AIM: We aimed to examine the frequency and the characteristics of immunoglobulin G4 (IgG4)-associated autoimmune hepatitis among pediatric patients with autoimmune hepatitis. METHODS: Immunostaining for IgG and IgG4 was performed in liver biopsies of 40 pediatric patients with autoimmune hepatitis. The patients with more than 10 IgG4-positive plasma cells/high-power field were defined as IgG4-associated autoimmune hepatitis. Clinic, laboratory, and histopathological results were compared between groups. RESULTS: Among the 40 pediatric patients, 34 patients were type 1 and 6 patients were type 2 autoimmune hepatitis. Six patients (15%), four of the type 1 and two of the type 2 autoimmune hepatitis patients, were diagnosed with IgG4-associated autoimmune hepatitis. Clinical, laboratory, and histopathological data were initially similar in both forms. There was a positive correlation between IgG4-positive plasma cell count and degree of portal (r: 0.406, P: 0.009) and lobular inflammation (r: 0.37, P: 0.019), grade of interface hepatitis (r: 0.33, P: 0.03), and fibrosis (r: 0.318, P: 0.046). Time required for normalization of liver transaminases and serum IgG level was significantly shorter in IgG4-associated autoimmune hepatitis (3.3 ± 0.5 vs 6.6 ± 3.5 for alanine aminotransferase, 3.7 ± 0.8 vs 6.7 ± 1.2 for aspartate aminotransferase, 4.3 ± 1.2 vs 7.1 ± 2.7 for gamma-glutamyl transpeptidase, and 7.2 ± 3.1 vs 12.8 ± 4.5 for IgG). CONCLUSIONS: Immunoglobulin G4-associated autoimmune hepatitis can be found in pediatric age group and also in type 2 autoimmune hepatitis patients. As steroid response may be better in IgG4-associated autoimmune hepatitis, biopsy specimens should be evaluated for this entity at diagnosis.

Assessment of cardiac function and electrocardiographic findings in patients with Wilson's disease.

BACKGROUND: This study evaluated cardiac function using tissue Doppler echocardiography and assessed electrocardiographic findings in children diagnosed with Wilson's disease. METHOD: Asymptomatic patients with a diagnosis of Wilson's disease (n = 43) were compared to healthy controls (n = 37) that were age and gender matched. RESULTS: The standard electrocardiographic and conventional echocardiographic examinations were similar in both groups. The left ventricular ejection fraction, shortening fraction, and diastolic function were not significantly different between the two groups. The Tei index for mitral lateral, mitral septal, tricuspid lateral, tricuspid septal, and inter-ventricular septum on tissue Doppler echocardiography was higher in the patient group, yet it did not reach statistical significance. Mitral lateral and septal systolic annular velocity values were significantly lower in the patient group when compared to the control group (p = 0.02 and 0.04, respectively). Also, mitral lateral and septal isovolumetric contraction time values were higher in the patient group (p = 0.04). Although the left ventricular values were not significantly different, relative left ventricular wall thickness was higher in the patient group when compared to the control group, and concentric remodelling in the left ventricle was found in 7 (16%) of 42 patients. QT interval (p = 0.02) and P-wave dispersion values (p = 0.04) were significantly higher in the patient group compared to the control group, and these tend to predict arrhythmias. CONCLUSION: Our study based on the tissue Doppler echocardiography assessment indicated a subclinical systolic, rather than diastolic, dysfunction in the myocardium with increased QT interval and P-wave dispersion, despite the young age of the patients and short disease duration.

ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome.

INTRODUCTION: Adenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. We planned to evaluate their clinical and laboratory findings before and after enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (aHSCT), and hematopoietic stem cell gene therapy (HSCGT). METHODS: Measurement of ADA enzyme activity and metabolites and sequencing of the ADA gene were performed in most of the patients with ADA deficiency. One of the patients with late-onset ADA deficiency was diagnosed by the help of primary immunodeficiency panel screening. RESULTS: Ten out of 13 patients were diagnosed as SCID, while 3 out of 13 were diagnosed as delayed-/late-onset ADA deficiency. Late-onset ADA deficiency patients had clinical and laboratory findings of combined immunodeficiency (CID). Eight patients with ADA-SCID were found to have higher levels of ADA metabolite (dAXP%) (62.1% (34.6-71.9)) than 3 patients with delayed-/late-onset ADA deficiency (6.9% (2.1-8.9). All but one patient with SCID had T-B-NK- phenotype, one had T-B-NK+ phenotype. Genetic defect was documented in 11 patients. Four out of 11 patients had compound heterozygous defects. Three out of 4 patients with compound heterozygous defects had delayed-onset/late-onset ADA deficiency. Seven out of 11 patients with SCID had homozygous defects. Five out of 7 had the same homozygous indel frameshift mutation (c.955-959delGAAGA) showing a founder effect. There were two novel splice site defects: one (IVS10+2T>C) was heterozygous in a patient with late-onset ADA deficiency, and the other was homozygous (IVS2delT+2) in a SCID patient. Other defects were missense defects. Nine out of 13 patients were put on pegylated ADA ERT. Four out of six patients were transplanted without using a conditioning regimen. HSCGT was performed to one of the patients. CONCLUSION: The genetic diagnosis of SCID is utmost important. There is a chance to give ERT before the definitive therapy if the patient with SCID/CID has ADA deficiency. Although ERT was insufficient to restore a normal immune function in ADA-SCID patients, it was useful to improve and stabilize the clinical status before curative therapy (aHSCT/HSCGT). Enzyme replacement therapy was successful in patients with late-/delayed-onset ADA deficiency who presented with the features of combined immunodeficiency. Gastrointestinal polyposis in a patient with late-onset ADA deficiency may be an association or a coincidental finding. Intermittent neurodevelopmental evaluation especially for hearing impairment should be performed in most of the ADA-deficient patients. This may alleviate the speech delay and cognitive abnormalities which may be observed in the follow-up.

Liver transplantation from a deceased donor with ß-thalassemia intermedia is not contraindicated: A case report.

The use of extended criteria donors who might have previously been deemed unsuitable is an option to increase the organ supply for transplantation. This report presents a pediatric case of a successful liver transplantation from a donor with ß-thalassemia intermedia. A patient, 6-year-old female, with a diagnosis of cryptogenic liver cirrhosis underwent deceased donor liver transplantation from a thalassemic donor. Extreme hyperferritinemia was detected shortly after transplantation. The most probable cause of hyperferritinemia was iron overload secondary to transplantation of a hemosiderotic liver. Hepatocellular injury due to acute graft rejection might have contributed to elevated ferritin levels by causing release of stored iron from the hemosiderotic liver graft. Iron chelation and phlebotomy therapies were started simultaneously in the early postoperative period to avoid iron-related organ toxicity and transplant failure. Follow-up with monthly phlebotomies after discharge yielded a favorable outcome with normal transplant functions. Thalassemia intermedia patients can be candidates of liver donors to decrease pretransplant waitlist mortality. After transplantation of a hemosiderotic liver, it is important to monitor the recipient in terms of iron overload and toxicity. Early attempts to lower iron burden including chelation therapy and/or phlebotomy should be considered to avoid organ toxicity and transplant failure.

Niemann-Pick disease type C in the newborn period: a single-center experience.

Niemann-Pick disease type C (NPC) is a neurovisceral lysosomal storage disorder with a great variation in clinical spectrum and age at presentation. Clinical features of 10 NPC patients who presented in the newborn period between 1993 and 2015 at our center were retrospectively analyzed. Males and females were equally distributed; there was a history of parental consanguinity (n = 8) and first-degree relative with NPC (n = 3). Patients were symptomatic between 1 and 10 days (mean 3.6 ± 2.6 days). Age at diagnosis was between 1 and 30 days (mean 14.6 ± 13.3 days). Laboratory work-up included bone marrow aspiration (n = 8) and/or filipin staining (n = 4). Confirmation was done by molecular analysis, indicating NPC1 (n = 8) and NPC2 (n = 2) mutations. All patients had neonatal cholestasis and hepatosplenomegaly. Pulmonary involvement (n = 9) and fetal ascites (n = 2) were additional accompanying features. All but one died due to pulmonary complications (n = 6) and liver insufficiency (n = 3) between 1.5 and 36 months of age (mean 8.1 ± 10.8 months). Currently, one patient is alive at the age of 11 months without any neurological deficit. CONCLUSIONS: Neonatal presentation is a rare form of NPC with exclusively visceral involvement in the newborn period and poor prognosis leading to premature death due to pulmonary complications and liver failure. What is known: • Neonatal presentation is a rare form of NPC with exclusively visceral involvement in the newborn period and poor prognosis leading to premature death. • Progressive liver disease is the most common cause of death among neonatal-onset NPC patients. What is new: • Natural course of neonatal-onset NPC may show variations. • Pulmonary involvement should be considered as an important cause of death in neonatal-onset cases, and appropriate precautions should be taken to prevent complications of respiratory insufficiency and airway infections.

Intractable diarrhea of infancy: 10 years of experience.

OBJECTIVES: Intractable diarrhea of infancy (IDI), a group of prolonged diarrheal disorders, is difficult to diagnose and manage. We documented general features of patients and the causes of IDI. METHODS: The present retrospective study included 60 hospitalized patients with IDI ages 0 to 24 months during January 2000 to December 2010. Detailed history, laboratory and endoscopic findings, diagnoses, and clinical courses were reviewed. Descriptive analyses were used for statistical evaluation. RESULTS: The male/female ratio was 1.4. The median age at onset of diarrhea was 12 days. A total of 70% and 11% of patients were severely and moderately malnourished, respectively. Carbohydrate malabsorption (CM) and food allergies (n = 11, 18% for both) were the most frequent causes. A total of 16 of the patients (27%) did not have a specific diagnosis. The other diagnoses were infections (n = 5), immune-mediated disorders (IMD) (n = 6), congenital enterocyte defects (CED) (n = 3, 5%), short bowel syndrome (n = 2), cystic fibrosis (n = 2), intestinal pseudoobstruction (n = 1), congenital disorder of glycosylation (n = 1), abetalipoproteinemia (n = 1), and proprotein convertase (PC) 1 deficiency (n = 1). Stool calprotectin level was high in 10 of 19 patients with Crohn disease (n = 3, mean 1116 ± 851 mg/L), food allergy (n = 4, mean 516 ± 288 mg/L), and undefined etiology (n = 3, mean 616 ± 780 mg/L). The mean duration of hospitalization was 76 days. CONCLUSIONS: IDI is a heterogeneous group of diarrheal disorders. The most frequent causes were CM and food allergies in our study. Because high levels of calprotectin support inflammation, calprotectin levels may help to discriminate CED and inflammatory causes of IDI.

Esophageal stricture due to recurrent mucositis in a patient with acute lymphoblastic leukemia.

An esophageal stricture is one of the complications that may develop during cancer treatment in children. Although more commonly associated with radiotherapy, recurrent mucositis has also been implicated. Presented herein is a case of a patient with acute lymphoblastic leukemia who suffered recurrent attacks of severe mucositis. Initial management of ensuing dysphagia included antifungal treatment for candida esophagitis. A subsequent upper endoscopy due to persistence of dysphagia revealed the presence of an esophageal stricture. Our aim in presenting this case is to emphasize the importance of considering a diagnosis of esophageal stricture in patients receiving anti-cancer treatment; early endoscopic intervention may be warranted in some patients.

Serum alpha-fetoprotein levels in neonatal cholestasis.

Alpha-fetoprotein (AFP) is used as a tumor marker for hepatocellular carcinoma, hepatoblastoma and germ cell tumors. It may also be elevated in infants with some hepatobiliary disorders. The mechanism of AFP elevation in neonatal cholestasis is not known. We retrospectively evaluated serum AFP levels in 53 infants with neonatal cholestasis. Thirty patients (56.6%) had elevated AFP, and the ratio of patients with elevated AFP was significantly high in both the metabolic diseases and idiopathic neonatal hepatitis groups (p=0.021). Serum aspartate aminotransferase (AST) levels increased significantly in patients with elevated AFP (p=0.004). Steatosis was the distinctive histopathological finding of the patients with high AFP. The patients with steatosis had significantly higher standard deviation (SD) score of AFP than the patients without steatosis (p=0.001). We have shown AFP elevation in neonatal cholestasis due to metabolic disorders and idiopathic neonatal hepatitis and its association with steatosis and AST elevation.

The significance of MUAC z-scores in diagnosing pediatric malnutrition: A scoping review with special emphasis on neurologically disabled children.

This review by a panel of pediatric gastroenterology-hepatology-nutrition and pediatric neurology experts aimed to address the significance of mid-upper arm circumference (MUAC) assessment in diagnosis of pediatric malnutrition. Specifically, the potential utility of recently developed MUAC z-score tape in clinical practice for larger patient populations was addressed including the neurologically disabled children. In accordance with the evidence-based data, four statements were identified by the participating experts on the utility of MUAC z-score tape, including (1) MUAC z-scores correlate with body mass index (BMI) and weight for height/length (WFH/l) z-scores in diagnosing malnutrition; (2) MUAC z-score tape offers a higher sensitivity to diagnose the mild and moderate malnutrition and better ability to track the changes in nutritional status over time than the other single datapoint measurements; (3) Using single-step MUAC z-score tape in children with cerebral palsy (CP) seems to provide more reliable data on anthropometry; and (4) The clinical value of the tool in classifying secondary malnutrition in CP should be investigated in large-scale populations. In conclusion, enabling single-step estimation of nutritional status in a large-scale pediatric population regardless of age and within a wide range of weight, without formal training or the need for ancillary reference charts and calculators, MUAC z-tape offers a favorable tool for easier and earlier diagnosis of pediatric malnutrition. Nonetheless, further implementation of MUAC z-score screening in larger-scale and/or special populations is necessary to justify its utility in relation to other primary anthropometric indicators in diagnosis of malnutrition as well as in treatment monitoring in the community and hospital setting.

Additional diverse findings expand the clinical presentation of DOCK8 deficiency.

We describe seven Turkish children with DOCK8 deficiency who have not been previously reported. Three patients presented with typical features of recurrent or severe cutaneous viral infections, atopic dermatitis, and recurrent respiratory or gastrointestinal tract infections. However, four patients presented with other features. Patient 1-1 featured sclerosing cholangitis and colitis; patient 2-1, granulomatous soft tissue lesion and central nervous system involvement, with primary central nervous system lymphoma found on follow-up; patient 3-1, a fatal metastatic leiomyosarcoma; and patient 4-2 showed no other symptoms initially besides atopic dermatitis. Similar to other previously reported Turkish patients, but in contrast to patients of non-Turkish ethnicity, the patients' lymphopenia was primarily restricted to CD4(+) T cells. Patients had homozygous mutations in DOCK8 that altered splicing, introduced premature terminations, destabilized protein, or involved large deletions within the gene. Genotyping of remaining family members showed that DOCK8 deficiency is a fully penetrant, autosomal recessive disease. In our patients, bone marrow transplantation resulted in rapid improvement followed by disappearance of viral skin lesions, including lesions resembling epidermodysplasia verruciformis, atopic dermatitis, and recurrent infections. Particularly for patients who feature unusual clinical manifestations, immunological testing, in conjunction with genetic testing, can prove invaluable in diagnosing DOCK8 deficiency and providing potentially curative treatment.

Evaluation of lansoprazole as a probe for assessing cytochrome P450 2C19 activity and genotype-phenotype correlation in childhood.

PURPOSE: Lansoprazole, a cytochrome P450 2C19 (CYP2C19) substrate, has been widely used in children to manage acid-related diseases. CYP2C19 exhibits marked genetic polymorphisms, and distribution of these polymorphisms varies among different ethnic groups. There is limited data regarding the use of probe drugs for determining CYP2C19 activity in children. The aim of this study was to evaluate lansoprazole as an in vivo phenotyping probe for assessing CYP2C19 activity in children. METHODS: The CYP2C19*2, *3, and *17 variants were determined in 244 children. Three hours after a single oral dose of lansoprazole (n = 94) or omeprazole (n = 19), plasma lansoprazole and 5-hydroxy lansoprazole or omeprazole and 5-hydroxy omeprazole concentrations were analyzed by high-performance liquid chromatography. RESULTS: The CYP2C19*17 was the most frequent variant allele (24.4%). The group of patients with CYP2C19*17*17 genotype had a 70% lower (p < 0.05) mean lansoprazole plasma concentration compared with the CYP2C19*1*1 genotype group, whereas the CYP2C19*2*2 group had 6.9-fold higher (p < 0.01) mean lansoprazole plasma concentration. Lansoprazole metabolic ratios (lansoprazole/5-hydroxy-lansoprazole) were found to be significantly lower in the *17*17 [mean ± standard deviation (SD); 2.8 ± 2.1] group and higher in the *2*2 group (63.5 ± 12.2) compared with that of the *1*1 genotype group (6.1 ± 4.5). CONCLUSION: According to our results from a Turkish pediatric population, lansoprazole is a suitable probe drug for phenotyping CYP2C19. The CYP2C19*2 and *17 variants should be taken into consideration in predicting the clinical outcome of therapy with lansoprazole in the pediatric population.

Cytokine profile in serum and gingival crevicular fluid of children with inflammatory bowel disease: A case-control study.

BACKGROUND: To evaluate the cytokine profile in gingival crevicular fluid (GCF) and serum of pediatric inflammatory bowel disease (IBD) patients and determine the cluster patterns of cytokines. METHODS: Fifty IBD patients and 21 systemically healthy children were enrolled in the study. The GCF samples were collected from the participants during periodontal examination and periodontal indices were recorded. Based on activity indexes and response to conventional treatment, patients with IBD were further categorized into subgroups as: remission, active disease, and treatment-resistant. Serum samples were obtained from IBD patients to determine serum levels of cytokines. The levels of pro- (interleukin (IL)-1ß, IL-12, IL-21, IL-22, IL-23, IL-17A, IL-17F) and anti-inflammatory (IL-4, IL-10) cytokines in serum and GCF were measured using Enzyme-linked Immunosorbent Assay (ELISA) kits. RESULTS: Among 50 IBD patients, 58% were in remission, 20% had active disease, and 22% were defined as treatment-resistant. The severity of gingival inflammation measured by the criteria of Löe had increasing trends in IBD patients with active disease and treatment resistance. GCF IL-1ß level was lower and GCF IL-4 and GCF IL-23 levels were higher in IBD patients compared to healthy controls. In the active disease group, more cytokine clusters occurred compared to the control group and other IBD subgroups, as explained by increased cytokine-cytokine interactions. CONCLUSIONS: Considering the increased complexity of cytokine interactions and the increased severity of gingival inflammation in patients with active disease, it can be concluded that disease activity might have an impact on gingival inflammation in pediatric patients with IBD.

Immunoglobulin abnormalities and effects of enzyme replacement therapy in children with Gaucher disease.

Hyperimmunoglobulinemia is documented in patients with Gaucher disease of all ages. We investigated the frequency of hyperimmunoglobulinemia in 12 pediatric patients with type I and III Gaucher disease and the effects of enzyme replacement therapy on these abnormalities. The incidence of hyperimmunoglobulinemia was 77%, 66%, and 60% at the diagnosis, before and after ERT, respectively. Immunoglobulin G abnormalities were the most commonly seen isotype abnormality. After enzyme replacement therapy normalization of IgA and IgM levels were recorded but decline in IgG levels was less likely to occur. This study indicated the higher frequency of hyperimmunoglobulinemia in pediatric Gaucher patients.

Obesity in adolescents with celiac disease: two adolescents and two different presentations.

Celiac disease (CD) usually presents with diarrhea and growth retardation in childhood. Obesity is one of the paradoxical conditions in children with CD. We present two adolescents with CD and obesity. One of these patients was diagnosed as CD with malnutrition. His body weight had returned to normal after a gluten-free diet, and after stopping the diet, he had become obese. The second patient was an obese adolescent presenting with dyspeptic symptoms who was diagnosed as CD. Although rare, pediatricians should remember that obesity might be seen in CD before or after the diagnosis.

Outcome of enzyme replacement therapy in Turkish patients with Gaucher disease: does late intervention affect the response?

We aimed to evaluate the outcome of enzyme replacement therapy (ERT) in Turkish Gaucher patients since it first became available in our country. Eleven patients with type I and one patient with type III Gaucher disease (GD) received therapy as 30-60 U/kg and 120 U/kg every two weeks, respectively, for at least six months, starting a mean period of 4.2 years after the diagnosis. Assessment of response included serial measurements of hematological and biochemical parameters and liver and spleen volumes. Symptoms and signs of bone disease, growth and severity scores were also evaluated. ERT in Turkish patients led to marked improvement in hematological parameters and organomegaly in the majority of them. Patients with growth failure demonstrated catch-up growth. Progression of bone disease was not observed except in two patients who experienced a delay of 15 and 8.6 years, respectively, between the diagnosis and the start of ERT.

Nutritional Support in Malnourished Children With Compromised Gastrointestinal Function: Utility of Peptide-Based Enteral Therapy.

This review focuses on nutritional support in malnourished children with compromised gastrointestinal function addressing the interplay between malnutrition and gastrointestinal dysfunction, and the specific role of peptide-based enteral therapy in pediatric malnutrition. Malnutrition is associated with impaired gut functions such as increased intestinal permeability, malabsorption, and diarrhea, while pre-existing functional gastrointestinal disorders may also lead to malnutrition. Presence of compromised gastrointestinal function in malnourished children is critical given that alterations such as malabsorption and increased intestinal permeability directly interfere with efficacy of nutritional support and recovery from malnutrition. Appropriate nutritional intervention is the key step in the management of malnutrition, while alterations in gastrointestinal functions in malnourished children are likely even in those with mild degree malnutrition. Therefore, nutritional therapy in children with compromised gastrointestinal function is considered to involve gut-protective interventions that address the overlapping and interacting effects of diarrhea, enteropathy and malnutrition to improve child survival and developmental potential in the long-term. Peptide-based enteral formulas seem to have clinical applications in malnourished children with compromised gastrointestinal function, given their association with improved gastrointestinal tolerance and absorption, better nitrogen retention/ balance, reduced diarrhea and bacterial translocation, enhanced fat absorption, and maintained/restored gut integrity as compared with free amino acid or whole-protein formulas.

Clinical-genetic characteristics and treatment outcomes of Turkish children with Gaucher disease type 1 and type 3: A sixteen year single-center experience.

Data from 38 children were retrospectively analyzed to determine the patient characteristics of Turkish children with Gaucher disease (GD) and evaluate the impact of enzyme replacement therapy (ERT) in a pediatric cohort consisting of two different sub-types of the disease, Gaucher disease type 1 (GD1) and type 3 (GD3). Both types were represented equally (GD1/GD3 = 20/18). L444P (35.5%) was the most common mutant allele while L444P/L444P (34.2%) was the most common genotype overall. Compound heterozygosity of N370S and L444P homozygosity were the dominant genotypes in Turkish children with GD1 and GD3, respectively. None of the patients had moderate to severe thrombocytopenia at last follow-up while the percent of patients with anemia decreased from 60% to 5.7% (p < 0.001). Significant improvements in mean liver (from 2.2 to 1.6 MN, p < 0.001) and spleen (from 15.5 to 7.6 MN, p < 0.001) volumes were observed in the first year of ERT. Linear growth was ameliorated as shown by the decrease in the percent of patients having short stature from 34.3% to 13.3% (p < 0.01) at year 5. Erlenmeyer flask deformity, osteopenia and scoliosis were common skeletal findings. Although none of the patients had lung disease at diagnosis, 20% developed radiological findings suggestive of pulmonary involvement. This single center experience is the first comprehensive study from Turkey not only reporting clinical and genetic characteristics of GD patients but also providing information on the outcomes of ERT in two different sub-types of GD. Genotypic background of Turkish children with GD is similar to western populations. Although visceral and hematological therapeutic goals are reached as early as one year of ERT in both sub-types, achieving normal growth takes several more years than suggested in significant number of children with GD.