Co-existence of phenylketonuria either with maple syrup urine disease or Sandhoff disease in two patients from Iran: emphasizing the role of consanguinity
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Maryam Abiri
und
Sirous Zeinali
Abstract
Most inborn errors of metabolism (IEMs) are inherited in an autosomal recessive manner. IEMs are one of the major concerns in Iran due to its extensive consanguineous marriages. Herein, we report two patients with two co-existent IEMs: a girl affected by classic phenylketonuria (PKU) and maple syrup urine disease (MSUD) and a male patient affected with Sandhoff disease and PKU, where Sandhoff disease was suspected due to the presence of a cherry-red spot in the eyes at 6 months which is unrelated to PKU. Sequencing of candidate genes in the first patient revealed one novel and three recurrent compound heterozygous mutations of p.Ser231Pro and p.Ala300Ser in the PAH gene and p.Glu330Lys and p.Arg170Cys mutations in the BCKDHB gene. Genetic testing results in the second patient showed previously reported homozygous mutations of p.Arg261Gln in the PAH and p.Arg533Cys mutation in the HEXB gene. Genetic testing confirmed the clinical diagnosis of both diseases in both patients. To the best of our knowledge; this is the first report of the co-existence of two distinct genetic disorders in two individuals from Iran. Co-existent different IEMs in patients complicated the clinical diagnosis and management of the diseases.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Chuang DT, Shih VE. Maple syrup urine disease (branchedchain ketoaciduria). In: Scriver CR Beaudet AL, Valle D, editors. CB, Kinzler KW, Vogelstein B, (assoc eds), editors. The metabolic and molecular basis of inerited disease. New York: Mc Graw-Hil, 2001:1971–2006.Suche in Google Scholar
2. Abiri M, Karamzadeh R, Karimipoor M, Ghadami S, Alaei MR, et al. Identification of six novel mutations in Iranian patients with maple syrup urine disease and their in silico analysis. Mutat Res 2016;786:34–40.10.1016/j.mrfmmm.2016.01.005Suche in Google Scholar
3. Ali EZ, Yunus ZM, Desa NM, Hock NL. Identification of a novel homozygous mutation (S144I) in a Malay patient with maple syrup urine disease. J Pediatr Endocrinol Metab 2013;26: 975–80.10.1515/jpem-2012-0424Suche in Google Scholar
4. Kleiman FE, de Kremer RD, de Ramirez AO, Gravel RA, Argaraña CE. Sandhoff disease in Argentina: high frequency of a splice site mutation in the HEXB gene and correlation between enzyme and DNA-based tests for heterozygote detection. Hum Genet 1994;94:279–82.10.1007/BF00208283Suche in Google Scholar
5. Venselaar H, Te Beek TA, Kuipers RK, Hekkelman ML, Vriend G. Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces. BMC Bioinformatics 2010;11:548.10.1186/1471-2105-11-548Suche in Google Scholar
6. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.10.1093/nar/16.3.1215Suche in Google Scholar
7. Den Dunnen JT, Antonarakis SE. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 2000;15:7–12.10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-NSuche in Google Scholar
8. Dianzani I, Knappskog PM, de Sanctis L, Giannattasio S, Riva E, et al. Novel missense mutation in the phenylalanine hydroxylase gene leading to complete loss of enzymatic activity. Hum Mutat 1995;6:247–9.10.1002/humu.1380060308Suche in Google Scholar
9. Eisensmith RC, Woo SL. Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene. Hum Mutat 1992;1:13–23.10.1002/humu.1380010104Suche in Google Scholar
10. Miryounesi M, Ghafouri-Fard S, Goodarzi H, Fardaei M. A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD). J Pediatr Endocrinol Metab 2015;28:673–5.10.1515/jpem-2014-0341Suche in Google Scholar
11. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, et al. A method and server for predicting damaging missense mutations. Nat Methods 2010;7:248–9.10.1038/nmeth0410-248Suche in Google Scholar
12. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009;4:1073–81.10.1038/nprot.2009.86Suche in Google Scholar PubMed
13. Aldahmesh MA, Abu-Safieh L, Khan AO, Al-Hassnan ZN, Shaheen R, et al. Allelic heterogeneity in inbred populations: the Saudi experience with Alström syndrome as an illustrative example. Am J Med Genet A 2009;149:662–5.10.1002/ajmg.a.32753Suche in Google Scholar PubMed
14. King RJ, Motulsky AG. Approach to genetic basis of common diseases. In: King RJ, Motulsky AG, editors. The genetic basis of common diseases, 2nd ed. New York, NY, USA: Oxford University Press, 2002:1076.Suche in Google Scholar
15. Saadat M, Ansari-Lari M, Farhud DD. Consanguineous marriage in Iran. Ann Hum Biol 2004;31:263–9.10.1080/03014460310001652211Suche in Google Scholar PubMed
16. Youssefian L, Vahidnezhad H, Aghighi Y, Ziaee V, Zeinali S, et al. Hyaline fibromatosis syndrome: a novel mutation and recurrent founder mutation in the CMG2/ANTXR2 gene. Acta Derm Venereol 2016.10.2340/00015555-2459Suche in Google Scholar PubMed
17. Youssefian L, Vahidnezhad H, Barzegar M, Li Q, Sotoudeh S, et al. The Kindler syndrome: a spectrum of FERMT1 mutations in iranian families. J Invest Dermatol 2015;135:1447.10.1038/jid.2015.9Suche in Google Scholar PubMed
18. Youssefian L, Vahidnezhad H, Daneshpazhooh M, Abdollahzadeh S, Talari H, et al. Lipoid proteinosis: phenotypic heterogeneity in Iranian families with c. 507delT mutation in ECM1. Exp Dermatol 2015;24:220–2.10.1111/exd.12620Suche in Google Scholar PubMed
©2016 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
- An update on thyroid-associated ophthalmopathy in children and adolescents
- Mini Review
- Systematic review and meta-analysis of the association between mumps during childhood and risk of type 1 diabetes mellitus
- Original Articles
- Glycemic variability predicts inflammation in adolescents with type 1 diabetes
- Prevalence and risk factors for diabetic retinopathy in a hospital-based population of Australian children and adolescents with type 1 diabetes
- One month of omega-3 fatty acid supplementation improves lipid profiles, glucose levels and blood pressure in overweight schoolchildren with metabolic syndrome
- The outcome of seven patients with hereditary tyrosinemia type 1
- Increased oxidative stress parameters in children with moderate iodine deficiency
- Relationship between 25(OH)D levels and circulating lipids in African American adolescents
- Endoglin and obestatin levels, cardiometabolic risk factors and subclinical atherosclerosis in children aged 10–18 years
- Lipoprotein-associated phospholipase A2 activity and low-density lipoprotein subfractions after a 2-year treatment with atorvastatin in adolescents with type 1 diabetes
- Genetic characteristics and long-term follow-up of 11 patients with congenital hyperinsulinism followed in a single center
- Pituitary volume in children with growth hormone deficiency, idiopathic short stature and controls
- Case Reports
- A novel insulin receptor mutation in an adolescent with acanthosis nigricans and hyperandrogenism
- Primary hyperparathyroidism may masquerade as rickets-osteomalacia in vitamin D replete children
- Co-existence of phenylketonuria either with maple syrup urine disease or Sandhoff disease in two patients from Iran: emphasizing the role of consanguinity
- Severe malnutrition causing superior mesenteric artery syndrome in an adolescent with Triple A syndrome
- Solving a case of allelic dropout in the GNPTAB gene: implications in the molecular diagnosis of mucolipidosis type III alpha/beta
Artikel in diesem Heft
- Frontmatter
- Review
- An update on thyroid-associated ophthalmopathy in children and adolescents
- Mini Review
- Systematic review and meta-analysis of the association between mumps during childhood and risk of type 1 diabetes mellitus
- Original Articles
- Glycemic variability predicts inflammation in adolescents with type 1 diabetes
- Prevalence and risk factors for diabetic retinopathy in a hospital-based population of Australian children and adolescents with type 1 diabetes
- One month of omega-3 fatty acid supplementation improves lipid profiles, glucose levels and blood pressure in overweight schoolchildren with metabolic syndrome
- The outcome of seven patients with hereditary tyrosinemia type 1
- Increased oxidative stress parameters in children with moderate iodine deficiency
- Relationship between 25(OH)D levels and circulating lipids in African American adolescents
- Endoglin and obestatin levels, cardiometabolic risk factors and subclinical atherosclerosis in children aged 10–18 years
- Lipoprotein-associated phospholipase A2 activity and low-density lipoprotein subfractions after a 2-year treatment with atorvastatin in adolescents with type 1 diabetes
- Genetic characteristics and long-term follow-up of 11 patients with congenital hyperinsulinism followed in a single center
- Pituitary volume in children with growth hormone deficiency, idiopathic short stature and controls
- Case Reports
- A novel insulin receptor mutation in an adolescent with acanthosis nigricans and hyperandrogenism
- Primary hyperparathyroidism may masquerade as rickets-osteomalacia in vitamin D replete children
- Co-existence of phenylketonuria either with maple syrup urine disease or Sandhoff disease in two patients from Iran: emphasizing the role of consanguinity
- Severe malnutrition causing superior mesenteric artery syndrome in an adolescent with Triple A syndrome
- Solving a case of allelic dropout in the GNPTAB gene: implications in the molecular diagnosis of mucolipidosis type III alpha/beta
