Clinical Manifestations of Type 1 Gaucher Disease

 How to Cite this Article: Salehpour Sh. Clinical Manifestations of Type 1 Gaucher Disease. Iran J Child Neurol Autumn 2012; 6:4 (suppl. 1):13-14.pls see PDF.References 1. Beutler E, Grabowski GA. Gaucher disease. In: Metabolic and molecular bases of inherited disease, Scriver CR, Beaudet AL, Sly WS, Valle D (Eds), McGraw-Hill, New York 2001: 3635. 2. Cox TM, Schofield JP.   Gaucher’s disease: clinical features  and   natural   history.   Baillieres   Clin Haematol. 1997 Dec;10(4):657-89.  

Leigh Disease

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Diagnostic Methods for Gaucher Disease

How to Cite This Article: Salehpour Sh. Diagnostic Methods for Gaucher Disease. Iran J Child Neurol. 2015 Autumn;9:4(Suppl.1): 14-15.Pls see Pdf.

Diagnostic Methods for Neimann-Pick Type C

How to Cite This Article: Salehpour Sh. Diagnostic Methods for Neimann-Pick Type C. Iran J Child Neurol. 2015 Autumn;9:4(Suppl.1): 16-17. Pls see pdf.

Clinical Manifestations of Organic Acidemia

A clinical presentation of a metabolic disorder, often first seen in infants who present with poor feeding, vomiting, tachypnea, acidosis, hyperammonemia, ketosis, ketonuria, irritability, and convulsions or hypotonia and lethargy, findings that are otherwise suggestive of neonatal sepsis Diseases with OA Isovaleric and propionic acidemias, maple syrup urine disease, medium chain acyl dehydrogenase deficiency, glutaric, methylmalonic, formiminoglutamic acidurias.DescriptionThe term “organic acidemia” or “organic aciduria” (OA) applies to a diverse group of metabolic disorders characterized by the excretion of non-amino organic acids in urine. Most organic acidemias results from a dysfunction of a specific step in amino acid catabolism, usually due to deficient enzyme activity. This leads to the accumulation of organic acids in the biological fluids (blood and urine), which, in turn, produces disturbances in the acid-base balance and causes alterations in pathways of intermediary metabolism.Methylmalonic acidemia occurs when the activity of Methylmalonyl CoA mutase is defective in the isoleucine, valine, methionine and threonine degradative pathway.Propionic acidemia occurs when the activity of Propionyl CoA carboxylase isdefective in the isoleucine, valine, methionine and threonine degradative pathway.Isovaleric acidemia occurs when the activity of Isovaleryl CoA dehydrogenase is defective in the leucine degradative pathway.Glutaric acidemia type I occurs when the activity of Glutaryl CoA dehydrogenase is defective in the lysine, hydroxylysine and tryptophan degradative pathway.3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) lyase deficiency occurs when the activity of HMG CoA lyase is defective in the leucine degradative pathway.3-Methylcrotonyl CoA carboxylase deficiency occurs when the activity of 3-methylcrotonyl-CoA carboxylase is defective in the leucine degradative pathway.IncidenceWhile each individual disorder is rare, overall incidence of organic acidemias is 1:20, 000.Clinical FeaturesA neonate affected with an organic acidemia is usually well at birth and for the first few days of life. The usual clinical symptoms of OA disorders may include vomiting, metabolic acidosis, ketosis, dehydration, coma, hyperammonemia, lactic acidosis, hypoglycemia, failure to thrive, hypotonia, global developmental delay, sepsis and hematologic disorders. The non-distinct clinical presentation may initially be attributed to sepsis, poor breast-feeding, or neonatal asphyxia.ScreeningNewborn Screening Laboratory performs a screening test for organic acidemias by tandem mass spectrometry (MS/MS). It is a screening test and not a diagnostic test. Confirmatory TestingA diagnosis must be confirmed using an independent analysis of urinary organic acids as well as other appropriate tests.It is important to confirm or exclude the diagnosis of an organic acidemia in a timely fashion and with a high degree of accuracy to avoid unnecessary testing, to provide appropriate interventions, prognostic and genetic counseling, and to ensure access to specialized medical services.Implications for Genetic TestingThe disorders included in this screening are inherited in an autosomal recessive manner. While a family history of neonatal death should prompt consideration of an organic acidemia, a negative family history does not preclude the possibility.Interpretations/RecommendationsMandated Disorders:• Expected Results: No elevated markers for C3, C5, C5DC, and C5OH (Acylcarnitine Profile within acceptable limits)• Equivocal Results: Indeterminate results Recommend: Repeat filter paper specimen within 2 days• Presumptive-Positive Results: Elevated acylcarnitine markers indicating a possible organic acidemia or repeat equivocal results Glutaric acidemia type I – C5DC Propionic and Methylmalonic acidemia – C3 Isovaleric acidemia – C5 3-Hydroxy-3-methylglutaryl CoA lyase deficiency – C5OH 3-Methylcrotonyl CoA carboxylase deficiency – C5OHRecommend: Immediate assessment of the baby’s health status and consultation with metabolic/genetic specialist strongly recommended.Non-Mandated Disorders:Other acylcarnitine markers detected on MS/MS• Positive Results: An elevated acylcarnitine result that does not match a mandated organic acidemia disorder profile Recommend: Immediate assessment of the baby’s health status and consultation with a metabolic/genetic specialist for appropriate urine and/or serum confirmatory/diagnostic testing and treatment Newborn screening tests are adjuncts to clinical assessment, which is paramount. An organic acidemia disorder should be considered in infants with any of the signs/symptoms regardless of newborn screening results.

The Effect of Cinnamon Supplementation on Hemoglobin A1c in Patients with Type 1 Diabetes Mellitus

Introduction: Type 1 diabetes mellitus (T1DM), one of the most common endocrine disorders in children, is an autoimmune disease that manifests itself as an increase in blood sugar as a result of impaired insulin production due to the destruction of the islets of Langerhans in the pancreas. To treat this disease, along with the use of insulin and numerous drug protocols, the use of herbal medicinal supplements has always been considered. However, due to the lack of studies related to these supplements, there is not enough evidence for their therapeutic use. Method: We investigated the therapeutic effectiveness of a cinnamon medicinal supplement with a dose of 50 mg every 8 hours per day, on glucose hemostasis in patients with T1DM . Thirty patients with T1DM were enrolled. They are subjected to sampling and examination of blood sugar indicators, including fasting blood sugar and hemoglobin A1c, as well as indicators of insulin consumption (total daily dose of insulin) and insulin resistance, including the ratio of insulin to carbohydrates on days 0, 90 and 180 of the start of treatment with cinnamon. Results:  The level of hemoglobin A1c in this group had a significant decrease. Also, there was no significant increase in the amount of insulin consumption in the drug supplement-consuming groups in contrast to the control group during six months. Conclusion: The use of cinnamon supplements along with treatment protocols has a significant effect in reducing hemoglobin A1c during six months of treatment in these patients. These results can be useful in promoting the use of therapeutic supplements in the treatment of patients with diabetes

Association of a Novel Nonsense Mutation in KIAA1279 with Goldberg-Shprintzen Syndrome

How to Cite This Article: Salehpour Sh, Hashemi-Gorji F, Soltani Z, Ghafouri-Fard S, Miryounesi M. Association of a Novel Nonsense Mutation in KIAA1279 with Goldberg-Shprintzen Syndrome. Iran J Child Neurol. Winter 2017; 11(1):70-74.AbstractGoldberg-Shprintzen syndrome (OMIM 609460) (GOSHS) is an autosomal recessive multiple congenital anomaly syndrome distinguished by intellectual disability, microcephaly, and dysmorphic facial characteristics. Most affected individuals also have Hirschsprung disease and/or gyral abnormalities of the brain. This syndrome has been associated with KIAA1279 gene mutations at 10q22.1. Here we report a 16 yr old male patient referred to Center for Comprehensive Genetic Services, Tehran, Iran in 2015 with cardinal features of GOSHS in addition to refractory seizures. Whole exome sequencing in the patient revealed a novel nonsense (stop gain) homozygous mutation in KIAA1279 gene (KIAA1279: NM_015634:exon6:c.C976T:p.Q326X).Considering the wide range of phenotypic variations in GOSHS, relying on phenotypic characteristics for discrimination of GOSH from similar syndromes may lead to misdiagnosis. Consequently, molecular diagnostic tools would help in accurate diagnosis of such overlapping phenotypes.References1. Goldberg R, Shprintzen R. Hirschsprung megacolon and cleft palate in two sibs. J Craniofac Genet Dev Biol 1980;1(2):185-9. 2. Yomo A, Taira T, Kondo I. Goldberg-Shprintzen syndrome: Hirschsprung disease, hypotonia, and ptosis in sibs. Am J Med Genet 1991;41(2):188-91.3. Drevillon L, Megarbane A, Demeer B, Matar C, Benit P, Briand-Suleau A, et al. KBP-cytoskeleton interactions underlie developmental anomalies in Goldberg-Shprintzen syndrome. Hum Mol Genet 2013;22(12):2387-99.4. Brooks AS, Bertoli-Avella AM, Burzynski GM, Breedveld GJ, Osinga J, Boven LG, et al. Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems. Am J Med Genet 2005;77(1):120-6.5. Blatch GL, Lassle M. The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. BioEssays 1999;21(11):932-9.6. Alves MM, Burzynski G, Delalande J-M, Osinga J, van der Goot A, Dolga AM, et al. KBP interacts with SCG10, linking Goldberg–Shprintzen syndrome to microtubule dynamics and neuronal differentiation. Hum Mol Genet 2010:ddq280.7. Valence S, Poirier K, Lebrun N, Saillour Y, Sonigo P, Bessières B, et al. Homozygous truncating mutation of the KBP gene, encoding a KIF1B-binding protein, in a familial case of fetal polymicrogyria. Neurogenetics2013;14(3-4):215-24.8. Murphy HR, Carver MJ, Brooks AS, Kenny SE, Ellis IH. Two brothers with Goldberg-Shprintzen syndrome. Clinl Dysmorphol 2006;15(3):165-9

Molecular Investigation of Glutaric Aciduria Type1 in Iran

Glutaric Acidemia, Type I (GA I), was first described in 1975. The disease is caused by a genetic deficiency of the enzyme, Glutaryl-CoA Dehydrogenase (GCD), which leads to the buildup of Glutaric acid in the tissues and its excretion in the urine of affected patients. GCD is involved in the catabolism of the amino acids, Lysine, Hydroxylysine, and Tryptophan. Over 200 cases of GA I have been reported in the medical literature. GA I is one of the most common organic acidemias and has an estimated incidence of about 1 in 50,000 live births.Because of the initial slow progression of clinical symptoms, GA I is frequently undiagnosed until an acute metabolic crisis occurs. A total of 25 unrelated patients suspected to GA1 were investigated in our study. Genomic DNA was extracted from peripheral blood cells of the 25 probands whom were biochemically and/or clinically and/or neuro-radiologically suspected to GA1. 15 of them had elevated glutaric acid in the urine organic acid test.PCR and direct sequencing of all 11 exons and their flanking region of the GCDH gene were examined.Some of them were investigated for known mutation in the other their family members. Fifteen patients had homozygous mutations and 10 patients were normal for GCDH gene. Our Results Showed:• 60% Known mutation were found in our 15 patients• 80% can be detected by 4 exons sequencing so for molecular investigatins exon 6, 7, 8, 10 are good choice for beginning of analysis• 33% was mutation in exon 7, so because of the cost of genetic diagnosis we suggest that investigation begin with this exon.• Pro 348 Leu was most detected 20%.• 40% are new mutations wich will be investigated for phenotype Genotype Correlations

Effect of growth hormone on muscle strength, tone and mobility of children with Prader-Willi syndrome

ObjectivePrader-Willi Syndrome (PWS) is a genetic syndrome presenting with severe hypotonia and decreased agility. Growth Hormone (GH), which is often used in these patients to treat short stature and obesity, seems improve hypotonia, physical strength, activity, and locomotor developmental ability. The aim ofthis study was to find the effects of growth hormone on agility and strength of these patients.Material & MethodsIn a prospective randomized controlled clinical trial in an out-patient pediatric endocrine clinic in Tehran, 21 PWS children (12 boys and 9 girls, 4 to 9 years old) were divided into either GH-treated or control groups and followed for two years. Agility run, sit ups, weight lifting, and inspiratory and expiratory strength were considered as the main outcome measures.ResultsAll the outcome measures of the GH treated group showed a significant improvement compared to the control group.ConclusionGH causes a significant improvement in agility and strength of PWS children.Key words: Preder-willi syndrome; PWS; growth hormone;agility; strengt

Three Novel Mutations in Iranian Patients with Tay-Sachs Disease

ABSTRACT Background: Tay-Sachs disease (TSD), or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population. Methods: In this study, we examined 31 patients for TSD-causing mutations using PCR, followed by restriction enzyme digestion. Results: Molecular genetics analysis of DNA from 23 patients of TSD revealed mutations that has been previously reported, including four-base duplications c.1274_1277dupTATC in exon 11 and IVS2+1G>A, deletion TTAGGCAAGGGC in exon 10 as well as a few novel mutations, including C331G, which altered Gln>Glu in HEXB, A>G, T>C, and p.R510X in exon 14, which predicted a termination codon or nonsense mutation. Conclusion: In conclusion, with the discovery of these novel mutations, the genotypic spectrum of Iranian patients with TSD disease has been extended and could facilitate definition of disease-related mutations