ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume : 13 Issue : 1 Year : 2023

Abstracting & Indexing
Turkish Society for Pediatric Endocrinology and Diabetes
Volume: 13  Issue: 1 - 2021

Pages I - XI

2.The Clinical Spectrum of Resistance to Thyroid Hormone Alpha in Children and Adults
İbrahim Mert Erbaş, Korcan Demir
doi: 10.4274/jcrpe.galenos.2020.2019.0190  Pages 1 - 14
Resistance to thyroid hormone alpha occurs due to pathogenic, heterozygous variants in THRA. The entity was first described in 2012 and to date only a small number of patients with varying severity have been reported. In this review, we summarize and interpret the heterogeneous clinical and laboratory features of all published cases, including ours. Many symptoms and findings are similar to those seen in primary hypothyroidism. However, thyroid-stimulating hormone levels are normal. Free triiodothyronine (T3) levels are in the upper half of normal range or frankly high and free thyroxine (T4) levels are low or in the lower half of normal range. Alterations in free T3 and free T4 may not be remarkable, particularly in adults, possibly contributing to underdiagnosis. In such patients, low reverse T3 levels, normo- or macrocytic anemia or, particularly in children, mildly elevated creatine kinase levels would warrant THRA sequencing. Treatment with L-thyroxine results in improvement of some clinical findings.

3.Catch-up Growth in Prepubertal Children Treated for Juvenile Hypothyroidism and Growth Hormone Deficiency can be Modelled with a Monomolecular Function
Jan M. Wit, Theo C. J. Sas, Paula van Dommelen
doi: 10.4274/jcrpe.galenos.2020.2020.0130  Pages 15 - 22
Objective: We hypothesized that modelling catch-up growth (CUG) as developed for coeliac disease (CD), might also fit CUG in adequately treated children with juvenile hypothyroidism (JHT) or growth hormone deficiency (GHD).
Methods: We used a monomolecular function for all available prepubertal data on height standard deviation score (HSDS) minus target height SDS (adjHSDS) in children with JHT (n=20) and GHD (n=18) on a conventional (CoD) or high GH dose (HD), based either on a national height reference with an age cut-off of 10 (girls) and 12 (boys) years (model 1) or prepubertal height reference values, if age (0) was ?3, with no upper age limit (model 2).
Results: The models could be fitted in 83-90% of cases; in other cases the HSDS decreased after several measurements, which violated the assumption of an irreversible growth process. In JHT, the rate constant (k) and adjHSDS (0) were lower than in CD (p=0.02), but adjHSDS (end) was similar. In GHD (model 1), k was lower than for CD (p=0.004) but similar to JHT, while adjHSDS (0) and adjHSDS (end) were similar to CD and JHT. Thus, the shape of CUG is similar for children with JHT and GHD, while children with CD had less growth deficit at start and a faster CUG. The differences in CUG parameters between GH dose subgroups did not reach statistical significance.
Conclusion: Modelling CUG of prepubertal children with JHT and GHD can be used for assessing the adequacy of CUG and the influence of clinical treatment modalities on its speed and magnitude.

4.Quality of Life and Psychological Well-being in Children and Adolescents with Disorders of Sex Development
Birsen Şentürk Pilan, Burcu Özbaran, Didem Çelik, Tuğçe Özcan, Samim Özen, Damla Gökşen, İbrahim Ulman, Ali Avanoğlu, Sibel Tiryaki, Hüseyin Onay, Özgür Çoğulu, Ferda Özkınay, Şükran Darcan
doi: 10.4274/jcrpe.galenos.2020.2020.0141  Pages 23 - 33
Objective: The aim of this study was to assess the quality of life (QoL) and psychological well-being in child and adolescent with disorders of sex development (DSD).
Methods: Sixty-two cases, aged 2-18 years, who were followed by a multidisciplinary DSD team were included. All participants and their parents were requested the complete the Pediatric Quality Of Life Inventory (PedsQL) and the Strengths and Difficulties Questionnaire. The psychiatric diagnoses of the patients were evaluated according to Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Turkish Version.
Results: There was no significant difference between the 46,XX DSD and 46,XY DSD groups for both child and parent in Total PedsQL score. In the subscale scores, the PedsQL Physical Functionality Score reported by children was significantly lower for the 46,XX DSD group than for the 46,XY DSD group (p=0.01). There was a psychiatric diagnosis in 25.8% of cases. The PedsQL School Functionality Score reported by children in the group with psychiatric diagnosis was significantly lower than the group without psychiatric diagnosis (p=0.018). In the group with psychiatric diagnosis, the PedsQL Total Score and the subscale scores (Emotional Functionality Score, Social Functionality Score, School Functionality) reported by parents were significantly lower than in parents of the group without psychiatric diagnosis.
Conclusion: This study emphasized that psychiatric disorders in DSD patients negatively affect the QoL. Psychiatric support and counseling from a multidisciplinary team are very important for families affected by DSD.

5.Identification of Three Novel and One Known Mutation in the Gene in Four Unrelated Turkish Families: The Role of Homozygosity Mapping in the Early Diagnosis
Maha Sherif, Hüseyin Demirbilek, Atilla Çayır, Sophia Tahir, Büşra Çavdarlı, Meliha Demiral, Ayşe Nurcan Cebeci, Doğuş Vurallı, Sofia Asim Rahman, Edip Unal, Gönül Büyükyılmaz, Riza Taner Baran, Mehmet Nuri Özbek, Khalid Hussain
doi: 10.4274/jcrpe.galenos.2020.2020.0152  Pages 34 - 43
Objective: Bi-allelic mutations in the wolframin gene (WFS1) cause Wolfram syndrome 1 (WS1 or DIDMOAD) characterized by non-autoimmune diabetes mellitus, optic atrophy, diabetes insipidus, sensorineural deafness, urinary tract abnormalities, and neuropsychiatric disorders. Patients presenting with an incomplete phenotype of WS1 were evaluated using homozygosity mapping and subsequent whole-exome sequencing.
Methods: Four unrelated consanguineous Turkish families, including seven affected children, and their unaffected parents and siblings were evaluated. Homozygosity mapping was performed, followed by whole-exome sequencing of WFS1. Mutations were classified according to results of “in silico” analyses, protein prediction, and functional consequences.
Results: Homozygosity mapping confirmed shared homozygous regions on chromosome 4 (chr4p16.1) between the affected individuals, that was absent in their unaffected siblings. Exome sequencing identified three novel (c.1215T>A, c.554G>A, c.1525_1540dup) and one known (c.1522_1523delTA) mutations in WFS1. All mutations were predicted to cause stop codon leading to early termination of protein synthesis and complete loss-of-function. All patients were found to be homozygous for the change, with parents and other unaffected siblings being carriers.
Conclusion: Our study expands the mutation spectrum of WSF1 mutations with three novel mutations. Homozygosity mapping may provide enrichment for molecular genetic analysis and early diagnosis of WS1 patients with incomplete phenotype, particularly in consanguineous pedigrees.

6.Very High Incidence of Type 1 Diabetes Among Children Aged Under 15 Years in Tlemcen, Northwest Algeria (2015-2018)
Sarra Khater, Ammaria Aouar, Nawel Bensmain, Salih Bendedouche, Nafissa Chabni, Houari Hamdaoui, Abdellatif Moussouni, Zakarya Moqaddem
doi: 10.4274/jcrpe.galenos.2020.2020.0073  Pages 44 - 51
Objective: In Algeria, there is a lack of epidemiological data concerning childhood type 1 diabetes (T1D). The International Diabetes Federation estimated in 2019 that Algeria ranked 7th among countries with the highest prevalence of T1D. This study aimed to determine the incidence of T1D in children <15 years, living in Tlemcen in Northwest Algeria.
Methods: A retrospective study using data from children (<15 years) who have been diagnosed with T1D in Tlemcen between 2015 and 2018, using the two-source capture–recapture method to estimate the completeness of ascertainment (%). Total average incidences, by sex, by onset age group, and by season of onset were calculated per 100,000 and per year.
Results: During the study period, 437 new cases of T1D were registered, among them, 233 boys and 204 girls, with a sex ratio of 1.14. The average annual incidence rate of childhood T1D was 38.5/100,000 with a 95% confidence interval (CI): 35.20-41.79; boys: 40.51, 95% CI: 38.16-42.85; girls: 36.49, 95% CI: 34.17-38.80. Overall incidence rates in 2015, 2016, 2017 and 2018 were respectively 36.6 (95% CI: 33.72-39.48), 38.7 (95% CI: 35.43-41.97), 39.3 (95% CI: 35.97-42.62) and 39.5 (95% CI: 36.12-42.87)/100,000. Newly diagnosed children were more likely to present in winter and autumn. Ketoacidosis at diagnosis was diagnosed in 29.2%.
Conclusion: The mean incidence of childhood T1D in Tlemcen was 38.5/100,000, this incidence is in the “extremely high” category of the World Health Organization DiaMond project classification of diabetes giving this region a very high risk.

7.A New Cause of Obesity Syndrome Associated with a Mutation in the Carboxypeptidase Gene Detected in Three Siblings with Obesity, Intellectual Disability and Hypogonadotropic Hypogonadism
Asude Durmaz, Ayça Aykut, Tahir Atik, Samim Özen, Durdugül Ayyıldız Emecen, Aysun Ata, Esra Işık, Damla Gökşen, Özgür Çoğulu, Ferda Özkınay
doi: 10.4274/jcrpe.galenos.2020.2020.0101  Pages 52 - 60
Objective: Carboxypeptidase E (CPE) plays a critical role in the biosynthesis of peptide hormones and neuropeptides in the endocrine system and central nervous system. CPE knockout mice models exhibit disorders such as diabetes, hyperproinsulinaemia, low bone mineral density and neurodevelopmental disorders. Only one patient is described with morbid obesity, intellectual disability, abnormal glucose homeostasis and hypogonadotropic hypogonadism, which was associated with a homozygous frameshift deletion in CPE.
Methods: Herein are described three siblings with obesity, intellectual disability and hypogonadotropic hypogonadism. Whole exome sequencing (WES) was performed in the index case. Candidate variants were prioritised and segregation of the variant, consistent with the phenotype of the index case, was assessed by Sanger sequencing in affected siblings and parents.
Results: WES analysis revealed a homozygous nonsense c.405C>A (p.Y135*) mutation in CPE. Validation and segregation analysis confirmed the homozygous mutation in the index case and his affected siblings. The parents were phenotypically normal heterozygous mutation carriers.
Conclusion: This study provides additional evidence of the association between a homozygous nonsense mutation in CPE and a clinical phenotype consisting of obesity, intellectual disability and hypogonadotropic hypogonadism, which may be considered as a new monogenic obesity syndrome.

8.Transforming Growth Factor-ß1 and Receptor for Advanced Glycation End Products Gene Expression and Protein Levels in Adolescents with Type 1 Diabetes Mellitus
Ana Ninic, Dragana Bojanin, Miron Sopic, Marija Mihajlovic, Jelena Munjas, Tatjana Milenkovic, Aleksandra Stefanovic, Jelena Vekic, Vesna Spasojevic-Kalimanovska
doi: 10.4274/jcrpe.galenos.2020.2020.0155  Pages 61 - 71
Objective: Type 1 diabetes (T1D) mellitus is one of the most frequent autoimmune diseases in childhood. Chronic complications are the main causes of cardiovascular morbidity and mortality in T1D. Although interactions between advanced glycation end products (AGE) and their receptors (RAGE) and transforming growth factor-ß1 (TGF-ß1) are implicated in development and progression of diabetic microand macro-vascular complications, they also have important roles in immune system regulation.
Methods: Blood samples were obtained from 156 adolescents with T1D and 80 apparently healthy controls. T1D patients diagnosed with any other autoimmune disease and receiving any kind of drugs except insulin therapy were excluded from this study. Exclusion criteria for controls were positive family history of T1D and drugs/supplements application. TGF-ß1 and transmembrane full-length RAGE (flRAGE) messenger ribonucleic acid (mRNA) levels in peripheral blood mononuclear cells (PBMC) were obtained by quantitative polymerase chain reaction (qPCR) method. Circulating levels of biochemical markers, TGF-ß1 and soluble RAGE (sRAGE) levels were also determined.
Results: TGF-ß1 and flRAGE mRNA levels were significantly higher in controls compared to patients (p<0.001, for both). However, TGF-ß1 and sRAGE levels were higher in patients than controls (p<0.001, for both). There were significant independent associations of all mRNA and protein levels with T1D. TGF-ß1 mRNA was the only marker independently negatively associated with urinary albumin excretion rate in T1D adolescents (p=0.005).
Conclusion: Our results indicated gene expression downregulation of TGF-ß1 and flRAGE in PBMC of T1D adolescents. TGF-ß1 mRNA downregulation may be useful for predicting early elevation of urinary albumin excretion rate.

9.Frequency of Celiac Disease and Spontaneous Normalization Rate of Celiac Serology in Children and Adolescent Patients with Type 1 Diabetes
Edip Unal, Meliha Demiral, Birsen Baysal, Mehmet Ağın, Elif Gökçe Devecioğlu, Hüseyin Demirbilek, Mehmet Nuri Özbek
doi: 10.4274/jcrpe.galenos.2020.2020.0108  Pages 72 - 79
Objective: he prevalence of celiac disease (CD) varies between 1% and 10% in patients with type 1 diabetes mellitus (T1DM). This study aimed to determine the frequency of spontaneous recovery of celiac serology and the biopsy-proven CD (BPCD) frequency in patients with T1DM.
Methods: The data of 668 patients with available celiac serology tests from a total of 779 patients who were followed for the last 10 years with the diagnosis of T1DM were retrospectively evaluated.
Results: Positive serology was detected in 103 out of 668 (15.4%) patients. There was spontaneous normalization in 24 (23.3%), fluctuation in 11 (10.7%) and permanently positive serology in 68 (66%). In 46 out of 53 (86.8%) patients with positive serology and biopsy, CD diagnosis was confirmed by biopsy (BPCD). The frequency of BPCD was 6.9%, and the serology in 76.1% was positive at the time of diagnosis of T1DM. The weight, height and body mass index-standard deviation score at diagnosis were lower in patients with BPCD compared to the group without CD. An anti-tissue transglutaminase-IgA (anti-TTG-IgA) level of 11.8 times the upper limit of normal was the most sensitive (93%) and specific (90%) cut-off for BPCD (area under the curve: 0.95; 95% confidence interval: 0.912-1; p<0.001).
Conclusion: In our cohort, the frequency of positive serology for CD was 15.4%, while the rate of BPCD was 6.9%. The majority (97.8%) of cases were diagnosed within the first five years of T1DM. In 23.3% of cases, positive anti-TTG-IgA spontaneously resolved without a gluten-free diet (GFD). Therefore, serological follow-up instead of immediate duodenal biopsy or GFD therapy, particularly for patients with asymptomatic and mild anti-TTG IgA level, is warranted.

10.Genotype and Phenotype Heterogeneity in Neonatal Diabetes: A Single Centre Experience in Turkey
Yasemin Denkboy Öngen, Erdal Eren, Özgecan Demirbaş, Elif Sobu, Sian Ellard, Ömer Tarım
doi: 10.4274/jcrpe.galenos.2020.2020.0093  Pages 80 - 87
Objective: eonatal diabetes mellitus (NDM) may be transient or permanent, and the majority is caused by genetic mutations. Early diagnosis is essential to select the patients who will respond to oral treatment. In this investigation, we aimed to present the phenotype and genotype of our patients with NDM and share our experience in a single tertiary center.
Methods: A total of 16 NDM patients from 12 unrelated families are included in the study. The clinical presentation, age at diagnosis, perinatal and family history, consanguinity, gender, hemoglobin A1c, C-peptide, insulin, insulin autoantibodies, genetic mutations, and response to treatment are retrospectively evaluated.
Results: The median age at diagnosis of diabetes was five months (4 days-18 months) although six patients with a confirmed genetic diagnosis were diagnosed >6 months. Three patients had KCNJ11 mutations, six had ABCC8 mutations, three had EIF2AK3 mutations, and one had a de novo INS mutation. All the permanent NDM patients with KCNJ11 and ABCC8 mutations were started on sulfonylurea treatment resulting in a significant increase in C-peptide level, better glycemic control, and discontinuation of insulin.
Conclusion: Although NDM is defined as diabetes diagnosed during the first six months of life, and a diagnosis of type 1 diabetes is more common between the ages of 6 and 24 months, in rare cases NDM may present as late as 12 or even 24 months of age. Molecular diagnosis in NDM is important for planning treatment and predicting prognosis. Therefore, genetic testing is essential in these patients.

11.Pediatric Primary Adrenal Insufficiency: A 21-year Single Center Experience
Emine Çamtosun, İsmail Dündar, Ayşehan Akıncı, Leman Kayaş, Nurdan Çiftçi
doi: 10.4274/jcrpe.galenos.2020.2020.0132  Pages 88 - 99
Objective: Primary adrenal insufficiency (PAI) is a rare but potentially life-threatening condition. In childhood, PAI is usually caused by monogenic diseases. Although congenital adrenal hyperplasia (CAH) is the most common cause of childhood PAI, numerous non-CAH genetic causes have also been identified.
Methods: Patients aged 0-18 years and diagnosed with PAI between 1998 and 2019 in a tertiary care hospital were retrospectively evaluated. After the etiologic distribution was determined, non-CAH PAI patients were evaluated in detail.
Results: Seventy-three PAI patients were identified. The most common etiology was CAH (69.9%, n=51). Non-CAH etiologies accounted for 30.1% (n=22) and included adrenoleukodystrophy (ALD; n=8), familial glucocorticoid deficiency (n=3), Triple A syndrome (n=5), autoimmune adrenalitis (n=1), adrenal hypoplasia congenital (n=1), IMAGe syndrome (n=1), and other unknown etiologies (n=3). The median age at the time of AI diagnosis for non-CAH etiologies was 3.52 (0.03-15.17) years. The most frequent symptoms/clinical findings at onset were hyperpigmentation of skin (81.8%), symptoms of hypoglycemia (40.9%), and weakness/fatigue (31.8%). Hypoglycemia (50.0%), hyponatremia (36.4%) and hyperkalemia (22.7%) were prominent biochemical findings. Diagnosis of specific etiologies were proven genetically in 13 of 22 patients. A novel p.Q301* hemizygous frameshift mutation of the DAX1 gene was identified in one patient.
Conclusion: Etiology was determined in 86.3% of children with non-CAH PAI through specific clinical and laboratory findings with/ without molecular analysis of candidate genes. ALD was the most common etiology. Currently, advanced molecular analysis can be utilized to establish a specific genetic diagnosis for PAI in patients who have no specific diagnostic features.

12.Homozygous Mutation in the Insulin Receptor Gene Associated with Mild Type A Insulin Resistance Syndrome: A Case Report
Bülent Hacihamdioğlu, Elif Gülşah Baş, Kenan Delil
doi: 10.4274/jcrpe.galenos.2020.2019.0213  Pages 100 - 103
Insulin receptor (INSR) mutations lead to heterogeneous disorders that may be as severe as Donohue syndrome or as mild as “type A insulin resistance syndrome”. Patients with severe disorders usually harbor homozygous or compound heterozygous mutations. In contrast, type A insulin resistance syndrome has been associated with heterozygous mutations; homozygous mutations are rarely responsible for this condition. We report a novel, homozygous mutation, p.Leu260Arg in exon 3, of the INSR gene in a female adolescent patient with type A insulin resistance syndrome together with clinical details of her medical follow-up. Different mutations in the INSR gene cause different phenotype and vary depending on the inheritance pattern. This report adds to the literature, increases understanding of the disease mechanism and aids in genetic counseling.

13.The Unusual Case of Fibroma of Tendon Sheath in a Young Girl with Turner Syndrome Undergoing Growth Hormone Treatment
Yong Hee Hong, Dong Gyu Kim, Jong Hyun Lee, Min Jung Jung, Chang Yong Choi
doi: 10.4274/jcrpe.galenos.2020.2019.0223  Pages 104 - 108
Fibroma of tendon sheath (FTS) is an uncommon mass that arises from the tendon sheath of extremities. The tumor typically affects adults between ages 20 and 50 years with a predominance in males. To date, growth hormone (GH) treatment is safe for children with Turner syndrome without risk factors and is accepted worldwide. This article reports the case of a nine-year-old female patient with Turner syndrome and FTS during GH treatment. She had been treated with daily subcutaneous GH to improve growth failure with a mean dose of 0.28 mg/kg/week and the level of insulin-like growth factor-1 was within the normal range. During the follow-up period, she complained about a mass in her hand, subsequently diagnosed as FTS. This report illustrates the clinical impact of Turner syndrome and GH treatments on the occurrence of this tumor through literature reviews. Further studies are needed to highlight the association between FTS and GH treatment, especially in Turner syndrome.

14.6q25.1-q25.3 Microdeletion in a Chinese Girl
Mian-Ling Zhong, Ye-Mei Song, Chao-Chun Zou
doi: 10.4274/jcrpe.galenos.2020.2020.0008  Pages 109 - 113
Deletions of the long arm of chromosome 6 are rare and are characterized by great clinical variability according to the deletion breakpoint. Herein, we reported a 3-year-old girl evaluated for facial dysmorphism (long and connected eyebrows, big mouth, wide nasal bridge, high palatine arch, low set ears, and thin hair), growth retardation, intellectual disability, and language delay. Chromosomal microarray analysis revealed an 8.1-Mb deletion within 6q25.1-q25.3 ([hg19] chr6: 152,307,705-160,422,834) comprising 31 genes. Dysmorphic features, microcephaly, intellectual disability, language delay, growth retardation, and corpus callosum dysgenesis were commonly reported. Hence, 6q25 microdeletion is a rare condition. In patients with dysmorphic features, microcephaly, growth retardation, intellectual disability, language delay and corpus callosum dysgenesis, 6q25 microdeletion should be considered in the differential diagnosis and chromosomal microarray analysis should be performed to confirm the diagnosis

15.Treatment Difficulties in Hypomagnesemia Secondary to the Transient Receptor Potential Melastatin 6 Gene: A Case Report with Novel Mutation
Hüsniye Yücel, Çiğdem Genç Sel, Çiğdem Seher Kasapkara, Gülin Karacan Küçükali, Senay Savas-Erdeve, Ülkühan Öztoprak, Serdar Ceylaner, Saliha Şenel, Meltem Akçaboy
doi: 10.4274/jcrpe.galenos.2020.2020.0004  Pages 114 - 118
Hypomagnesemia is a rare cause of seizures in childhood but should be kept in mind in recurrent and intractable seizures and hypocalcemia in communities where consanguineous marriages are common. Familial hypomagnesemia with secondary hypocalcemia is a rare genetic cause of hypomagnesemia, due to variants in the transient receptor potential melastatin 6 (TRPM6) genes. Here, a three year-old boy with a novel variant in this gene and had difficulties with enteral hypomagnesemia treatment is presented. He had recurrent seizures since two years of age and was diagnosed with epilepsy and treated with multiple antiepileptic drugs. Subsequently, he was diagnosed with rickets due to severe hypocalcemia at another center. The patient was hypotonic and neurodevelopmentally poor. The most prominent laboratory finding was of hypomagnesemia with secondary hypocalcemia. The genetic analysis revealed a novel variant in the TRPM6 gene. After parental treatment of intravenous magnesium (Mg2+) sulfate and calcium, the treatment was switched to enteral Mg2+ medications, due to persistent hypomagnesemia and the gastrointestinal side-effects, different oral preparations were used. The patient was stable on an oral maintenance dose of Mg2+ oxide with borderline blood Mg2+ levels and resolution of hypocalcemia. Hypomagnesemia is one of the causes of hypocalcemia. Enteral replacement is the key treatment but the treatment should be individualized for each patient. Normalization of hypomagnesemia is not always easy and should not be the aim of the treatment.

16.Sirolimus Therapy and Follow-up in a Patient with Severe Congenital Hyperinsulinism Following Subtotal Pancreatectomy
Qiong Chen, Yongxing Chen, Xiaohong Wang, Haihua Yang, Yingxian Zhang, Xiaojing Liu, Yun Yan, Haiyan Wei
doi: 10.4274/jcrpe.galenos.2020.2020.0033  Pages 119 - 123
Congenital hyperinsulinism (CHI) is the most common cause of severe, persistent hypoglycemia in neonates and infants. If the patient does not respond to medical treatment the currently available treatment is subtotal pancreatectomy, but some patients still experience severe hypoglycemia after surgery. Sirolimus, a mammalian target of rapamycin inhibitor has recently been reported to be effective in the treatment of insulinoma and CHI patients. Here we report a patient with CHI who had prolonged hypoglycemia after subtotal pancreatectomy. The patient had a heterozygous mutation in ABCC8 but was unresponsive to an optimal dose of diazoxide (15 mg/ kg/day) and octreotide (30 µg/kg/day). The patient subsequently had subtotal pancreatectomy but severe and persistent hypoglycemia continued post-operatively. Sirolimus was commenced. There was a remarkable improvement in glycemic control without major adverse events, although he required a small dose of octreotide to maintain euglycemia. Sirolimus therapy was discontinued when the patient was 15 months old. At the time of this report, at an age of three years and eight months, the patient continues to maintain good glycemic control. This report suggests that sirolimus may be an effective treatment option in patients with CHI resistant to established medical therapy or failure of subtotal pancreatectomy. However, the long-term safety requires study in larger groups of very young patients.

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