A novel mutation of Beta-ketothiolase deficiency: The first report from Iran and review of literature

Background:Beta-ketothiolase deficiency is a rare autosomal recessive disorder characterized by an inborn error of isoleucine catabolism and affecting ketone body metabolism. Clinical features characterized by intermittent keto acidotic episodes associated with clinical signs and symptoms of toxic encephalopathy such as lethargy, hypotonia, vomiting, tachypnea, and coma in some patients, with an onset during infancy or toddler-hood.Case presentation: A two months old girl presented with acute episode of fever and toxic encephalopathy with attack of vomiting, hypotonia, lethargy, tonic clonic seizures and then a day in coma, few days after vaccination .After then similar episodes happened until 7 months age.  . Biochemical tests that suggested diagnose of beta ketothiolase deficiency were attacks of ketoacidosis with urinary exertion of 2-methyl-3-hydroxybutric acid 2-methyl aceto acetic acid tiglylglycine. In genetic assessment we detected a novel homozygous mutation c.664A> C (p. Ser 222 Arg) in ACAT gene. This is a first report of beta ketothiolase deficiency confirmed by molecular analysis from Iran.Conclusion: we report on a homozygous variant in the ACAT1 gene that is the first time we detect this variant and is a novel mutation. According to the obtained result and patient’s phenotype, we recommended carrier testing for all informative family members to recognize mutations in asymptomatic family members

The Report of Three Rare Cases of the Niemann-pick Disease in Birjand, South Khorasan, Eastern Iran

How to Cite This Article: Noroozi Asl S, Vakili R, Ghaemi N, Eshraghi P. The Report of Three Rare Cases of the Niemann-pick Disease in Birjand, South Khorasan, Eastern Iran. Iran J Child Neurol. Summer 2017; 11(3):53-56. AbstractNiemann–Pick disease type C (NP-C) is a rare neurovisceral and irreversible disease leading to premature death and disabling neurological signs. This autosomal recessive disease with incidence rate of 1:120000 is caused by mutations in either the NPC1 or the NPC2 gene, which leads to accumulation of cholesterol in body tissues especially brain and progressive neurological symptoms. NP-C is characterized by nonspecific visceral, neurological and psychiatric manifestations in infants. The neurological involvement is typically proceeded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno-or hepatosplenomegaly in infancy or childhood).Early detection of NPC is important so that therapy with miglustat can delay onset of neurological symptoms and prolong survival. We describe here three infants from Birjand, South Khorasan, eastern Iran in 2016 with splenomegaly and different neurological signs that diagnosis was confirmed by genetic study. In all of them, NPC-509 was pathologically increased. They also had an unreported homozygous mutation (c. 1415T>C, p.Leu472Pro) in exon 9 of the NPC1 gene. We found unreported homozygous mutation in NPC gene.Knowing this mutation is significant to our people. Genotype-phenotype correlations for this specific mutation needs to be further studied. References1. Mengel E, Klunemann H, Lourenco C, and et al. Niemann-Pick disease type C symptomatology: an expert-based clinical description. Orphanet J Rare Dis 2013;8:166.2. Vanier MT: Niemann-Pick disease type C. Orphanet J Rare Dis 2010;5:16.3. Di Rocco M1, Dardis A, Madeo A, Barone R, Fiumara A. Early miglustat therapy in infantile Niemann-Pick disease type C. Pediatr Neurol 2012;47(1):40-3.4. Karimzadeh P, Tonekaboni SH, Ashrafi MR, et al. Effects of Miglustat on Stabilization of Neurological Disorder in Niemann–Pick Disease Type C Iranian Pediatric Case Series. J Child Neurol 2013;28(12):1599-606.5. Wijburg F, Sedel F, Pineda M et al. Development of a Suspicion Index to aid diagnosis of Niemann-Pick disease type C. Neurology 2012;78(20):1560-7.6. Wraith JE, Imrie J. New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat. Ther Clin Risk Manag 2009;5:877-87.7. Patterson M, Hendriksz Ch, Walterfang M, et al. Recommendations for the diagnosis and management of Niemann–Pick disease type C: An update. Mol Genet Metab 2012;106(3):330-44.8. Margaret M, Destinck DJ. Lipidosis(Lysosomal storage disease). Nelson Textbook of Pediatrics. 19th ed.Philadelphia: WB Saunders Company. 2011:488-9.9. Patterson M.C, Mengel E, Wijburg F, et al. Disease and patient characteristics in NP-C patients: findings from an international disease registry. Orphanet J Rare Dis 2013;8:12

Wiedemann-Steiner Syndrome with a 2-Year Follow-Up

Wiedemann-Steiner syndrome (WDSTS) is an exceptionally rare genetic syndrome characterized by postnatal growth retardation, facial dysmorphism, hairy elbow, and short stature. It is known that the occurrence of WDSTS is due to mutations in KMT2A gene. It is noteworthy that not a great number of WDSTS have been identified yet; thereby, new phenotypes and features continue to be added. In this report, we describe a 5-year-old male patient presented with developmental delay, hypothyroidism, facial dysmorphism, and behavioral signs such as autistic spectrum features. By Whole Exome Sequencing (WES), a new mutation in KMT2A was found and WDSTS was diagnosed genetically. According to a genetic test, a variant in exon 27 of the KMT2A gene c.6647delT (p.Pro2215fs) was found. This mutation was not reported previously, also this case was the first WDSTS diagnosed in Iran. This syndrome is a rare genetic disorder representing a broad range of phenotypes. The mentioned low frequency emphasizes the importance of a phenotype-genotype correlation to be established. The phenotype comparison between our case and previously reported patient did not reveal any difference related to age or sex in patients with WDST

Papillary Carcinoma Thyroid in a Nine-year-old Child: A Case Report

Thyroid enlargement and nodules are very rare in children, but when they occur, the chance of malignancy among these nodules is very high. Thyroid carcinoma is rare in childhood, but in the last two decades, its incidence has increased two-fold. A painless nodule in the neck is the most common presentation of the disease. Dysphagia, hoarseness, cervical lymphadenopathy, weight loss, and fatigue are other presentations. Surgical resection is the primary therapy for thyroid cancer. Levothyroxine and Iodine-131 (I131) are usually used as adjunctive therapy. This article presents the case of a 9-year-old girl who referred to our center with the chief complaint of a neck mass. Her symptoms had begun 6 months earlier

A Novel Heterozygous ACAN Variant in an Iranian Family with Short Stature: A Case Report

Background: Short stature is estimated to account for half of the new visits to pediatric endocrine practices. Therefore, evaluating its underlying causes seems essential in order to choose the best treatment. Recently, some studies revealed the impact of ACAN, which encodes for aggrecan, mutations on growth ranging from mild idiopathic short stature to severe skeletal dysplasia. Methods: Here, we describe clinical and molecular characteristics of an Iranian family with short stature using exome sequencing and co-segregation analysis through Sanger sequencing. Results: A novel variant of ACAN mutation c.1604delG (p.Arg535fs) was identified in the heterozygote pattern which was confirmed through co-segregation analysis in family members. Conclusion: We have found a novel variant within the ACAN gene in association with insignificant bone abnormality without a high incidence of familiar bone malformation. In order to achieve better clinical outcomes, we suggest genetic testing at an earlier age and also long-term GH treatment for children who are at risk of ACAN mutations. Children who are born small considering their gestational age, or who have persistent short stature, advanced bone age, midfacial hypoplasia, joint problems, or broad toes, can be candidates for ACAN sequencing

Mccune-Albright Syndrome: A Case Report Associated with Pamidronate Therapy and Literature Review

McCune-Albright Syndrome (MAS) is a rare sporadic disease characterized by bone fibrous dysplasia, Café au lait spots and a variable association of hyperfunction endocrine disorders. There is not any certain treatment available for this syndrome, and both physical and emotional disability in these patients is still a major concern for physicians. In present report we have described a 10- year-old girl, presented with precocious puberty, multiple Café au lait  macules and fibrous dysplasia, successfully treated with pamidronate in a four-year follow-up period

First Iranian Experience of the Minimally Invasive Nuss Procedure for Pectus Excavatum Repair: A Case Series and Literature Review

Pectus excavatum is the most common congenital deformity of the chest wall. The most frequently used techniques include Ravitch (costochondral resection) and Nuss (minimally invasive pectus repair of pectus excavatum [MIRPE]). The Nuss technique includes using temporary metallic bars without costochondral resection to correct the chest wall deformity. Modified MIRPE can be learned easily and performed safely with few complications. There are no reports of successful MIRPE in Iran, although the Ravitch technique is well known. In the present study, we report the first Iranian experience with the modified Nuss procedure in 5 patients with pectus excavatum (age range=13–48 y). All the patients suffered from low self-esteem, and one of them complained of low exercise capacity and occasional chest pain. With single-lung ventilation and sternal elevation, an introducer was entered into the right thoracic cavity and retrosternal tunneling was performed under thoracoscopic vision. The introducer was passed to the left thoracic cavity and exited on the left thoracic wall. A titanium plate bar was implanted and fixed with stabilizers. There were no cases of mortality, and all the patients were discharged in good conditions within 2 weeks. Postoperative complications consisted of 1 case of pneumothorax and 2 cases of fixed bar protrusion. The present case series indicated that a skilled thoracoscopic surgeon is able to do the Nuss procedure in Iranian patients with symmetrical pectus excavatum with few complications. However, mixed or redo cases require more expertise

Metabolic effects of fasting in adolescents with diabetes type 1

Type I diabetes mellitus is a common chronic disease in adolescents. According to statistics, 12,243 diabetic Muslims fast in thirteen Islamic countries, 43% of whom have type I diabetes. This longitudinal study was conducted on volunteer adolescents with type I diabetes aged 13-18 years for 15 days using the census method. Three days before Ramadan and during the last three days of the study period, changes in the insulin dose, HbA1C, lipid profile, and body mass index (BMI) were evaluated. Among 10 volunteer patients, eight individuals could complete Ramadan fasting. Blood glucose analysis indicated a significant difference between the reported blood glucose levels (

Validation of Urinary Glycosaminoglycans in Iranian patients with Mucopolysaccharidase type I: The effect of urine sedimentation characteristics

How to Cite This Article:Abdi M, Khatami Sh, Hakhamaneshi MS, Alaei MR, Azadi NA, Zamanfar D, Taghikhani M.Validation of Urinary Glycosaminiglycans in Iranian Patients with Mucopolysaccharidose Type I: The Effect of Urine Sedimentation Characteristics. Iran J Child Neurol. 2014; 8(4):39-45. AbstractObjectiveThe first line-screening test for mucopolysaccharidosis is based on measurement of urinary glycosaminoglycans. The most reliable test for measurement of urine glycosaminoglycans is the 1,9-dimethyleneblue colorimetric assay. Biological markers are affected by ethnical factors, for this reason, the World Health Organization recommends that the diagnostic test characteristics should be used to determine results for different populations. This study determines the diagnostic value of 1,9-dimethyleneblue tests for diagnosis of mucopolysaccharidosis type I patients in Iran.Materials & Methods In addition to routine urine analysis, the qualitative and quantitative measurements of urine glucosaminoglycans were performed with the Berry spot test and 1,9-dimethyleneblue assay. Diagnostic values of the tests were determined using the ROC curve.ResultsUrine total glycosaminoglycans were significantly higher in male subjects than in female subjects. Glycosaminoglycan concentration was markedly decreased in specimens with elevated white blood cell and epithelial cells count. Using a cut-off level of 10.37 mg/g creatinine, sensitivity, and specificity were 100% and 97.22%, respectively, for a 1,9-dimethyleneblue colorimetric assay.ConclusionUrine glycosaminoglycans concentration significantly differs in our studied population. In addition to determine diagnostic validity of the 1,9-dimethyleneblue test, our results demonstrate the usefulness of measuring glycosaminoglycans for early screening of mucopolysaccharidosis type I Iran. ReferencesJackson RL, Busch SJ, Cardin AD. Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiological reviews. 1991 Apr;71(2):481-539.Ghaderi S. The biochemistry base of mucopolysaccharidoses and approach to. Genetics in the 3rd millennium. [Educational]. 2006;4(1):711-22.Mizumoto S, Ikegawa S, Sugahara K. Human genetic disorders caused by mutations in genes encoding biosynthetic enzymes for sulfated glycosaminoglycans. The Journal of biological chemistry. 2013 Apr 19;288(16):10953-61.Salbach J, Rachner TD, Rauner M, Hempel U, Anderegg U, Franz S, et al. Regenerative potential of glycosaminoglycans for skin and bone. 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Placenta Site Trophoblastic Tumor and Choriocarcinoma from Previous Cesarean Section Scar: Case Reports

Choriocarcinoma and placental site trophoblastic tumor (PSTT) are rare varieties of gestational trophoblastic disease (GTD). PSTT alone constitutes about 1-2% of all trophoblastic tumors, which presents at early reproductive age and the serum beta-hCG level is much lower than choriocarcinoma. This tumor usually invades the myometrium and its depth of penetration is a prognostic factor. The first case report is regarding a 33-year-old woman with vaginal bleeding 3 months after abortion. The ultrasound exhibited heterogeneous and hypervascular mass related to previous cesarean scar. Serum beta-hCG level was 67 mIU/ml and chemotherapy was administered. However, due to severe vaginal bleeding and no regression in mass size, total abdominal hysterectomy was performed. Histopathological examination and IHC staining confirmed PSTT from previous cesarean section. The second case report is regarding a 33-year-old woman with cervicoisthmic choriocarcinoma, which was mistaken as cesarean scar pregnancy. The ultrasonography and elevated serum beta-hCG level suggested cesarean scar pregnancy. The patient was treated with methotrexate without any effect. Eventually, cervicoisthmic choriocarcinoma was detected after hysterectomy. A diagnostic error was made leading to possible uterus perforation along with incorrect chemotherapy that resulted in a life-threatening condition. It is concluded that PSTT and choriocarcinoma are the two important differential diagnoses of sustained elevated beta-hCG when imaging evidence is also suggestive. Although PSTT and cervicoisthmic choriocarcinoma are rare, they do exist and are on the rise