Hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d): cascade genetic screening in an affected family with HPRT1 c.584A> C mutation
Abstract: The hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d) is an inborn error in purine metabolism with X-linked inheritance responsible for Lesch-Nyhan disease (LND) and its attenuated variants (LNV). LND shows a totally enzymatic deficiency and it`s characteriz...
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| Formato: | Artículo revista |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2021
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/35076 |
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I10-R327-article-35076 |
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ojs |
| institution |
Universidad Nacional de Córdoba |
| institution_str |
I-10 |
| repository_str |
R-327 |
| container_title_str |
Revista de la Facultad de Ciencias Médicas de Córdoba |
| format |
Artículo revista |
| topic |
metabolic diseases hypoxanthine-guanine phosphoribosytransferase deficiency hyperuricemia mutation genetic screening enfermedades metabólicas enfermedad por deficiencia de hipoxantina-fosforribosil-transferasa hiperuricemia mutación cribado genético . |
| spellingShingle |
metabolic diseases hypoxanthine-guanine phosphoribosytransferase deficiency hyperuricemia mutation genetic screening enfermedades metabólicas enfermedad por deficiencia de hipoxantina-fosforribosil-transferasa hiperuricemia mutación cribado genético . Luna Pizarro , AG Grosso , CL Laróvere , LE Hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d): cascade genetic screening in an affected family with HPRT1 c.584A> C mutation |
| topic_facet |
metabolic diseases hypoxanthine-guanine phosphoribosytransferase deficiency hyperuricemia mutation genetic screening enfermedades metabólicas enfermedad por deficiencia de hipoxantina-fosforribosil-transferasa hiperuricemia mutación cribado genético . |
| author |
Luna Pizarro , AG Grosso , CL Laróvere , LE |
| author_facet |
Luna Pizarro , AG Grosso , CL Laróvere , LE |
| author_sort |
Luna Pizarro , AG |
| title |
Hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d): cascade genetic screening in an affected family with HPRT1 c.584A> C mutation |
| title_short |
Hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d): cascade genetic screening in an affected family with HPRT1 c.584A> C mutation |
| title_full |
Hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d): cascade genetic screening in an affected family with HPRT1 c.584A> C mutation |
| title_fullStr |
Hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d): cascade genetic screening in an affected family with HPRT1 c.584A> C mutation |
| title_full_unstemmed |
Hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d): cascade genetic screening in an affected family with HPRT1 c.584A> C mutation |
| title_sort |
hypoxanthine-guanine phosphoribosyltransferase deficiency (hprt-d): cascade genetic screening in an affected family with hprt1 c.584a> c mutation |
| description |
Abstract:
The hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d) is an inborn error in purine metabolism with X-linked inheritance responsible for Lesch-Nyhan disease (LND) and its attenuated variants (LNV). LND shows a totally enzymatic deficiency and it`s characterized by hyperuricemia, self-mutilation, neurodevelopmental delay, intellectual disability, etc. LNV show partial enzymatic deficiency resulting in hyperuricemia, gout, nephrolithiasis, renal failure and variable neurological compromise; these variants are considered to be underdiagnosed because they are misclassified as gout or hyperuricemic syndrome. Early diagnosis in hemizygous males is crucial to promptly start treatment with allopurinol in order to prevent severe kidney damage. Carrier identification is required to provide genetic counselling. Both presentations of the disease were diagnosed in our centre. This study was aimed to realize a cascade genetic screening to members of a family with a confirmed diagnosis of HPRT-d (LNV) and HPRT1 c.584A> C mutation. The study was performed in subjects with different degrees of kinship with a common 5 generations ancestor. This family originating from La Calera and Saldan has the antecedents of LNV cases with the HPRT1 c.584A> C mutation. Eight women and eight men were included; informed consent was obtained prior to blood extraction and genetic study. Identification of the HPRT1 c.584A> C mutation was carried out by PCR and restriction enzyme digestion to establish the genotype. Seven females were carriers and six males were hemizygous. Respect to positive cases, it was corroborated that 4 males had some symptoms related to hyperuricemia and 2 minors (aged 1 week and 1 year) without symptoms but with hyperuricemia subsequently confirmed. Although LND and its variants are rare diseases, they should be considered in the differential diagnosis of hyperuricemia. Cascade genetic screening in this family allowed us to make an early diagnosis of affected males and to establish treatment with allopurinol in order to prevent gouty manifestations and kidney failure. In women, the importance of identifying carriers for X-linked diseases is essential to provide genetic counselling in family planning.
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| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2021 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/35076 |
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2024-09-03T21:03:08Z |
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I10-R327-article-350762024-04-15T16:19:09Z Hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d): cascade genetic screening in an affected family with HPRT1 c.584A> C mutation Detección de la deficiencia de hipoxantina-guanina fosforribosiltransferasa: estudio genético en cascada familiar de la mutación HPRT1 c.584A>C A Luna Pizarro , AG Grosso , CL Laróvere , LE metabolic diseases hypoxanthine-guanine phosphoribosytransferase deficiency hyperuricemia mutation genetic screening enfermedades metabólicas enfermedad por deficiencia de hipoxantina-fosforribosil-transferasa hiperuricemia mutación cribado genético . Abstract: The hypoxanthine-guanine phosphoribosyltransferase deficiency (HPRT-d) is an inborn error in purine metabolism with X-linked inheritance responsible for Lesch-Nyhan disease (LND) and its attenuated variants (LNV). LND shows a totally enzymatic deficiency and it`s characterized by hyperuricemia, self-mutilation, neurodevelopmental delay, intellectual disability, etc. LNV show partial enzymatic deficiency resulting in hyperuricemia, gout, nephrolithiasis, renal failure and variable neurological compromise; these variants are considered to be underdiagnosed because they are misclassified as gout or hyperuricemic syndrome. Early diagnosis in hemizygous males is crucial to promptly start treatment with allopurinol in order to prevent severe kidney damage. Carrier identification is required to provide genetic counselling. Both presentations of the disease were diagnosed in our centre. This study was aimed to realize a cascade genetic screening to members of a family with a confirmed diagnosis of HPRT-d (LNV) and HPRT1 c.584A> C mutation. The study was performed in subjects with different degrees of kinship with a common 5 generations ancestor. This family originating from La Calera and Saldan has the antecedents of LNV cases with the HPRT1 c.584A> C mutation. Eight women and eight men were included; informed consent was obtained prior to blood extraction and genetic study. Identification of the HPRT1 c.584A> C mutation was carried out by PCR and restriction enzyme digestion to establish the genotype. Seven females were carriers and six males were hemizygous. Respect to positive cases, it was corroborated that 4 males had some symptoms related to hyperuricemia and 2 minors (aged 1 week and 1 year) without symptoms but with hyperuricemia subsequently confirmed. Although LND and its variants are rare diseases, they should be considered in the differential diagnosis of hyperuricemia. Cascade genetic screening in this family allowed us to make an early diagnosis of affected males and to establish treatment with allopurinol in order to prevent gouty manifestations and kidney failure. In women, the importance of identifying carriers for X-linked diseases is essential to provide genetic counselling in family planning. Resumen: La deficiencia de hipoxantina fosforribosiltransferasa (d-HPRT) es un defecto en el metabolismo de las purinas con herencia ligada al cromosoma X responsable de la Enfermedad de Lesch-Nyhan (ELN) y sus variantes (VLN). La ELN, con deficiencia total de la enzima, se caracteriza por hiperuricemia, automutilación, retraso del desarrollo, afectación neurológica, etc. La VLN con deficiencia parcial de la enzima, presenta hiperuricemia, gota, nefrolitiasis, fallo renal y variable grado de compromiso neurológico; esta variante se considera subdiagnosticada al clasificarla como gota o síndrome hiperuricémico. El diagnóstico precoz en varones hemicigotos es imprescindible para instaurar el tratamiento con alopurinol y evitar el daño renal; la identificación de portadoras permite realizar el correspondiente asesoramiento genético. Ambas formas de la enfermedad fueron diagnosticadas en nuestro medio. El objetivo del trabajo fue realizar un cribado genético en cascada a miembros de una familia con casos confirmados de d-HPRT (VLN) por mutación HPRT1 c.584A>C. El estudio estuvo dirigido sujetos con diferente grado de parentesco y un ancestro común de 5 generaciones; esta familia oriunda de La Calera y Saldán, tiene como antecedente casos de LNV con la mutación HPRT1 c.584A>C. Se incluyeron 8 mujeres y 8 varones, previo consentimiento informado para extracción de sangre y estudio genético. La identificación de la mutación HPRT1 c.584A>C se realizó por PCR y digestión con enzima de restricción para establecer el genotipo. De las mujeres analizadas 7 resultaron portadoras de la mutación y 6 varones hemicigotos; de estos casos positivos se corroboró que 4 presentaban alguna sintomatología relacionada a hiperuricemia y 2 menores (de 1 semana de vida y de 1 año) sin síntomas pero con hiperuricemia confirmada posteriormente. Aunque la ELN y sus variantes son enfermedades poco frecuentes, es importante considerarlas en el diagnóstico diferencial de hiperuricemia. El cribado genético en cascada familiar permitió realizar el diagnóstico precoz de los varones afectados e instaurar el tratamiento con alopurinol, evitando el desarrollo de manifestaciones gotosas e insuficiencia renal; en el caso de las mujeres, se resalta la importancia de identificar portadoras para enfermedades ligadas al X. . Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2021-10-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto texto https://revistas.unc.edu.ar/index.php/med/article/view/35076 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 78 No. Suplemento (2021): Suplemento JIC XXII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 78 Núm. Suplemento (2021): Suplemento JIC XXII Revista da Faculdade de Ciências Médicas de Córdoba; v. 78 n. Suplemento (2021): Suplemento JIC XXII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0 |