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.

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.

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.

Assessment of swallowing function in pediatric patients with Wilson's disease: Results of a videofluoroscopic swallowing study.

BACKGROUND AND STUDY AIMS: Wilson's disease (WD) is a complex disorder related to copper metabolism and neurological involvement may lead to swallowing disorders. The purpose of this study was to evaluate swallowing function in pediatric patients with WD by using videofluoroscopic swallowing study (VFSS). PATIENTS AND METHODS: A total of 21 patients were included in the study, prospectively. The VFSS was conducted to evaluate swallowing function of the patients. The penetration-aspiration scale (PAS) was used to assess penetration-aspiration severity. RESULTS: According to the VFSS, abnormal results were detected in nine patients (42.9%) with WD. Of these nine patients, oral phase dysfunction was present in one patient, laryngeal penetration was present in one patient and moreover, abnormal esophageal body function was detected in all nine patients. Of these nine patients, five had neurological presentation at the time of diagnosis, and remaining four patients had hepatic presentation. Mean PAS score of the patients was 1. CONCLUSION: The current study results suggest that subclinical swallowing dysfunction may be observed in patients with either neurological or hepatic WD. Further studies are necessary to reveal the real incidence of esophageal phase problems of swallowing function in pediatric patients with WD.

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.

A very rare cause of protein losing enteropathy: Gaucher disease.

BACKGROUND: Mesenteric lymphadenopathy is a rare manifestation of Gaucher disease (GD) in children and can be accompanied by protein losing enteropathy (PLE). PLE is a difficult-to-treat complication of GD. To date, only a few pediatric GD cases with PLE and massive mesenteric lymphadenopathies have been reported. CASE: Here, we report a girl with chronic neuronopathic GD, whose disease course was complicated by massive mesenteric lymphadenopathies with resultant protein losing enteropathy despite a regular and appropriate enzyme replacement therapy of 60 IU/kg/biweekly until the development of mesenteric lymphadenopathies and 120 IU/kg/biweekly thereafter. CONCLUSIONS: PLE is a devastating and life threatening complication of GD developing despite long term use of high dose ERT. Clinicians should be alert for this complication particularly in GD patients presenting with progressive abdominal distension, edema, ascites and diarrhea or in patients who have already developed mesenteric lymphadenopathies. Timely diagnosis may allow early intervention with previously suggested surgical or medical treatment options. Although there is no specific and effective treatment, surgical and aggressive medical interventions in addition to ERT were reported to relieve diarrhea and halt progression of mesenteric lymphadenopathies.

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.

The HLA groups and their relationship with clinical features in Turkish children and adolescents with celiac disease.

BACKGROUND: We aimed to investigate the relationship between human leukocyte antigens (HLA)-groups and clinical features, and degree of intestinal injury in children with celiac disease (CD). METHODS: Study group included 73 (50 females, 68.5%) children with CD. Demographic and clinical features, accompanying autoimmune diseases, family history for CD and degree of damage in small intestinal mucosa (according to Marsh classification) at the time of diagnosis were determined. Twenty-two siblings of celiac patients without CD (15 females, 65.2%) consisted control group 1, and 66 (40 females, 60.6%) people from the normal population consisted control group 2. RESULTS: The allele frequencies of HLA B8, B50, C6, C7, DR3, DR7, DQ2, and DR3 homozygosity were higher in the patient group. HLA DQ2 positivity was 89% in the patient group, 73.9 and 45.5% in control groups 1 and 2, respectively (p < 0.0001). HLA A30, C14, DR11, DQ3 frequency were lower in patients compared to both control groups. HLA-DR15 alleles in patient and control group 1 was significantly lower compared to the general population (p < 0.05). Thirty (41.1%) patients had typical, 43 (58.9%) patients had atypical presentation. Thirteen (17.8%) patients had other autoimmune diseases. There was no association between coexisting autoimmune diseases and the HLA antigens. Fifteen patients (20.5%) had a positive family history for CD; patients with HLA A69, B41 and C12 alleles had a higher positive family history (p < 0.05). Intestinal mucosal damage was as follows: 5 patients (6.8%) had Marsh 2, 25 (34.3%) Marsh 3a, 28 (38.4%) Marsh 3b, 15 (20.5%) Marsh 3c. Patients with HLA-DR15 alleles had more frequent Marsh 3a lesions (p < 0.05). CONCLUSIONS: B8, B50, C6, C7, DR3, DR7, DR3/DR3, DQ2 alleles were risk factors for CD in the Turkish population. HLA C14, DR11, DR15, and DQ3 alleles were found to have a protective role in the same population.

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.

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.

Revisiting long-term prognostic factors of biliary atresia: A 20-year experience with 81 patients from a single center.

BACKGROUND/AIMS: The present study aimed at investigating the long-term outcomes and prognostic factors of patients with biliary atresia (BA) diagnosed and followed at a single center. MATERIALS AND METHODS: Patients with BA treated during 1994-2014 at a large-volume pediatric tertiary referral center were reviewed retrospectively with regard to demographic, clinical, laboratory, and diagnostic characteristics for identifying the prognostic factors and long-term clinical outcomes. RESULTS: Overall, 81 patients (49 males, 32 females) were included. Mean age at diagnosis was 73.1±4.7 (median: 64) days. Of the patients included, 78 patients (96%) underwent a portoenterostomy procedure. Mean age at operation was 76.8±4.7 (median: 72) days. The surgical success rate was 64.8%. A younger age (either at diagnosis or surgery) was the only determinant of surgical success. The 2-, 5-, and 10-year overall survival (OS) rates, including all patients with or without liver transplantation, were 75%, 73%, and 71% respectively, whereas the 2-, 5-, and 10-year survival rates with native liver (SNL) were 69%, 61%, and 57%, respectively. Mean follow-up duration was 9.4±7.5 years. Successful surgery, presence of fibrosis and/or cirrhosis on the liver pathology, and prothrombin time [international normalized ratio (INR)] at presentation were independent prognostic factors for both OS and SNL. CONCLUSION: A younger age at diagnosis is strongly associated with surgical success in BA. Surgical success, the prothrombin time (INR) at presentation, and liver pathology are independent prognostic factors affecting the long-term outcomes in patients with BA. Therefore, timely diagnosis and early referral to experienced surgical centers are crucial for optimal management and favorable long-term results in BA.

Amoebic colitis presenting with hypo-albuminaemia in an eight-month-old breastfed girl.

Entamoeba histolytica is a protozoan parasite that affects a large proportion of the world's population and causes amoebic dysentery and extra-intestinal disease. Many individuals remain asymptomatic during colonisation; in 10% of individuals, the parasite breaks through the mucosal barrier and leads to invasive disease. An eight-month-old girl who was evaluated for hypo-albuminaemia and was diagnosed with amoebic colitis is reported. To the best of our knowledge, this is the first report of hypo-albuminaemia owing to amoebic colitis in any age group.

Coexistence or a related condition: an infant with retinoblastoma and Gaucher disease.

Berberoglu-Ates B, Varan A, Demir H, Akyüz C, Yüce A. Coexistence or a related condition: an infant with retinoblastoma and Gaucher disease. Turk J Pediatr 2019; 61: 449-452. Gaucher disease (GD) is the most prevalant lysosomal lipid storage disease that results from loss of function of acid ß-glucosidase due to mutations in the glucocerebrosidase gene. Common features of all types of GD include hepatosplenomegaly, cytopenia, and various patterns of bone and lung involvement. Retinoblastoma is a malignant tumor of the developing retina that occurs in children, typically before the age of five. Retinoblastoma develops from cells that have cancer-predisposing variants in both copies of RB1. The association between GD and retinoblastoma has not been reported until now. Here we report the case that was diagnosed with, retinoblastoma at the age of 2 months and then GD at the age of 11 months. Although there are controversies concerning the association between GD and cancer; malignancies should be kept in mind during GD patients follow up.

Long term follow-up of children with chronic hepatitis B: a single center experience.

Yaman Bajin I, Demir H, Saltik Temizel IN, Özen H, Yüce A. Long term follow-up of children with chronic hepatitis B: a single center experience. Turk J Pediatr 2019; 61: 846-851. Chronic Hepatitis B infection is an important clinical issue because of the associated risk of developing cirrhosis and hepatocellular carcinoma. Especially in children, there is no consensus about the optimal treatment. Clinical features and long-term outcomes of 165 children diagnosed with chronic hepatitis B at our institution between January 1993 and June 2012 were analysed retrospectively. Patients were divided into four groups according to their treatment protocols. The first group received Interferon (IFN) only, the second group started lamivudine (LMV) first then IFN+LMV combined and then continued with LMV only, the third group started with IFN+LMV combined then continued with LMV only and the fourth group received LMV only. After a median follow-up period of 7 years (1-19 years) the highest e-seroconversion (the loss of HBeAg followed by gain of anti- HBe antibody) rate, biochemical and virological response was observed with combined (IFN+LMV) treatment regimens. Patients with higher ALT levels were better treatment responders (p: 0.003). Identification of the patients who need to be treated in order to determine the most effective therapy with optimal treatment duration is important to reduce the risk of developing future complications like cirrhosis and hepatocellular carcinoma.

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.

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.

Application of Fourier transform infrared spectroscopy to biomolecular profiling of cultured fibroblast cells from Gaucher disease patients: A preliminary investigation.

BACKGROUND: Gaucher disease (GD) is defined as an autosomal recessive disorder resulting from the deficiency of glucocerebrosidase (E.C. 3.2.1.45). Glucocerebrosidase is responsible for the degradation of glucosylceramide into ceramide and glucose. The deficiency of this enzyme results in the accumulation of undegraded glucosylceramide, almost exclusively in macrophages. With Fourier transform infrared (FTIR) spectroscopy, the complete molecular diversity of the samples can be studied comparatively and the amount of the particular materials can be determined. Also, the secondary structure ratios of proteins can be determined by analysing the amide peaks. OBJECTIVES: The primary aim of this study is to introduce FTIR-ATR spectroscopy technique to GD research for the first time in the literature and to assess its potential as a new molecular method. MATERIAL AND METHODS: Primary fibroblast cell cultures obtained from biopsy samples were used, since this material is widely used for the diagnosis of GD. Intact cells were placed onto a FTIR-ATR crystal and dried by purging nitrogen gas. Spectra were recorded in the mid-infrared region between 4500-850 cm-1 wavenumbers. Each peak in the spectra was assigned to as organic biomolecules according to their chemical bond information. A quantitative analysis was performed using peak areas and we also used a hierarchical cluster analysis as a multivariate spectral analysis. RESULTS: We obtained FTIR spectra of fibroblast samples and assigned the biomolecule origins of the peaks. We observed individual heterogeneity in FTIR spectra of GD fibroblast samples, confirming the well-known phenotypic heterogeneity in GD at the molecular level. Significant alterations in protein, lipid and carbohydrate levels related to the enzyme replacement therapy were also observed, which is also supported by cluster analysis. CONCLUSIONS: Our results showed that the application of FTIR spectroscopy to GD research deserves more attention and detailed studies with an increased sample size in order to evaluate its potential in the diagnosis and follow-up of GD patients.

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.