Genetic and acquired defects of methylmalonic aciduria combined with homocystinuria in Argentine patients. A local experience
Combined methylmalonic aciduria and homocystinuria (MMA/HHCY) is an inborn error of cobalamin metabolism. Patients present with megaloblastic anemia, lethargy, growth-developmental delay, neurological deterioration, and seizures. Although it is considered a disease of infancy or childhood, some indi...
| Autores principales: | , , , , , , |
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| Formato: | Artículo revista |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2022
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/39089 |
| Aporte de: |
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I10-R327-article-39089 |
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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 |
methylmalonic aciduria homocystinuria B12 vitamin deficiency metabolism aciduria metilmalónica homocistinúria vitamina B12 deficiencia metabolismo . |
| spellingShingle |
methylmalonic aciduria homocystinuria B12 vitamin deficiency metabolism aciduria metilmalónica homocistinúria vitamina B12 deficiencia metabolismo . Grosso , CL Bezard, MB Angaroni, CL Becerra, AB Guelbert, GA Laróvere , LE Dodelson de Kremer , R Genetic and acquired defects of methylmalonic aciduria combined with homocystinuria in Argentine patients. A local experience |
| topic_facet |
methylmalonic aciduria homocystinuria B12 vitamin deficiency metabolism aciduria metilmalónica homocistinúria vitamina B12 deficiencia metabolismo . |
| author |
Grosso , CL Bezard, MB Angaroni, CL Becerra, AB Guelbert, GA Laróvere , LE Dodelson de Kremer , R |
| author_facet |
Grosso , CL Bezard, MB Angaroni, CL Becerra, AB Guelbert, GA Laróvere , LE Dodelson de Kremer , R |
| author_sort |
Grosso , CL |
| title |
Genetic and acquired defects of methylmalonic aciduria combined with homocystinuria in Argentine patients. A local experience |
| title_short |
Genetic and acquired defects of methylmalonic aciduria combined with homocystinuria in Argentine patients. A local experience |
| title_full |
Genetic and acquired defects of methylmalonic aciduria combined with homocystinuria in Argentine patients. A local experience |
| title_fullStr |
Genetic and acquired defects of methylmalonic aciduria combined with homocystinuria in Argentine patients. A local experience |
| title_full_unstemmed |
Genetic and acquired defects of methylmalonic aciduria combined with homocystinuria in Argentine patients. A local experience |
| title_sort |
genetic and acquired defects of methylmalonic aciduria combined with homocystinuria in argentine patients. a local experience |
| description |
Combined methylmalonic aciduria and homocystinuria (MMA/HHCY) is an inborn error of cobalamin metabolism. Patients present with megaloblastic anemia, lethargy, growth-developmental delay, neurological deterioration, and seizures. Although it is considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. It is a rare autosomal recessive disease in which there are several variants depending on the metabolic disorder (cblC, cblD, cblF and cblJ), the most frequent and severe is the cblC variant, caused by mutations in the MMACHC gene. In addition to the primary forms, there are forms acquired due to nutritional deficiencies. Infants from mothers with severe cobalamin deficiency during pregnancy and breastfeeding are at high risk of cobalamin deficiency. Early diagnosis and treatment are essential as they can alter the course and outcome of this disease. The objective is to present the experience in our Center of patients with MMA/HHCY, of acquired origin and due to a congenital error of cobalamin metabolism.
We present 27 defined patients with MMA/HHCY according to clinical manifestations, biochemical and molecular findings, maternal nutritional data, treatment and evolution. For this retrospective study (2005-2022), data were collected from the medical records of the patients studied at our Center. Urinary methylmalonic acid and plasmatic homocysteine were determined by chromatographic techniques in 100% of the patients; plasma amino acids, vitamin-B12 and acylcarnitines in most of them. Studies on the MMACHC and MMADHC genes in 6 and 2 patients, respectively; in 4, next-generation sequencing was performed.
Neurological manifestations predominated as presenting symptoms (59%, 16/27), followed by hematological symptoms 52% (14/27) and feeding difficulties 48% (13/27). Twenty-two patients received specific therapy and 59% (16/27) had rapid reversal of symptoms. The study of the MMACHC gene allowed us to identify 4 patients with the c.271dupA variant. Through a differential diagnostic algorithm, it was possible to classify 6 patients with an inborn error of metabolism and 16 patients with an acquired form (maternal nutritional deficiency).
Early diagnosis and treatment of MMA/HHCY, even when caused by cofactor deficiency, can favor the neurological prognosis of patients. |
| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2022 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/39089 |
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I10-R327-article-390892024-04-15T16:14:45Z Genetic and acquired defects of methylmalonic aciduria combined with homocystinuria in Argentine patients. A local experience Defectos genéticos y adquiridos de aciduria metilmalónica combinada con homocistinuria en pacientes argentinos. Una experiencia local. . Grosso , CL Bezard, MB Angaroni, CL Becerra, AB Guelbert, GA Laróvere , LE Dodelson de Kremer , R methylmalonic aciduria homocystinuria B12 vitamin deficiency metabolism aciduria metilmalónica homocistinúria vitamina B12 deficiencia metabolismo . Combined methylmalonic aciduria and homocystinuria (MMA/HHCY) is an inborn error of cobalamin metabolism. Patients present with megaloblastic anemia, lethargy, growth-developmental delay, neurological deterioration, and seizures. Although it is considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. It is a rare autosomal recessive disease in which there are several variants depending on the metabolic disorder (cblC, cblD, cblF and cblJ), the most frequent and severe is the cblC variant, caused by mutations in the MMACHC gene. In addition to the primary forms, there are forms acquired due to nutritional deficiencies. Infants from mothers with severe cobalamin deficiency during pregnancy and breastfeeding are at high risk of cobalamin deficiency. Early diagnosis and treatment are essential as they can alter the course and outcome of this disease. The objective is to present the experience in our Center of patients with MMA/HHCY, of acquired origin and due to a congenital error of cobalamin metabolism. We present 27 defined patients with MMA/HHCY according to clinical manifestations, biochemical and molecular findings, maternal nutritional data, treatment and evolution. For this retrospective study (2005-2022), data were collected from the medical records of the patients studied at our Center. Urinary methylmalonic acid and plasmatic homocysteine were determined by chromatographic techniques in 100% of the patients; plasma amino acids, vitamin-B12 and acylcarnitines in most of them. Studies on the MMACHC and MMADHC genes in 6 and 2 patients, respectively; in 4, next-generation sequencing was performed. Neurological manifestations predominated as presenting symptoms (59%, 16/27), followed by hematological symptoms 52% (14/27) and feeding difficulties 48% (13/27). Twenty-two patients received specific therapy and 59% (16/27) had rapid reversal of symptoms. The study of the MMACHC gene allowed us to identify 4 patients with the c.271dupA variant. Through a differential diagnostic algorithm, it was possible to classify 6 patients with an inborn error of metabolism and 16 patients with an acquired form (maternal nutritional deficiency). Early diagnosis and treatment of MMA/HHCY, even when caused by cofactor deficiency, can favor the neurological prognosis of patients. La aciduria metilmalónica y homocistinuria combinada (AMM/HHCI) es un error congénito del metabolismo de la cobalamina. Los pacientes presentan anemia megaloblástica, letargo, retraso del crecimiento-desarrollo, deterioro neurológico y convulsiones. Aunque se considera una enfermedad de la infancia o la niñez, algunas personas desarrollan síntomas en la adultez. Es una enfermedad autosómica recesiva en la que existen variantes según el defecto metabólico (cblC, cblD, cblF y cblJ), la más frecuente y grave es la variante cblC, causada por mutaciones en el gen MMACHC. Además de las formas primarias, existen formas adquiridas por deficiencias nutricionales. Los bebés de madres con deficiencia grave de cobalamina durante el embarazo y la lactancia tienen un alto riesgo de deficiencia de cobalamina. El diagnóstico y el tratamiento tempranos son fundamentales ya que pueden alterar el curso y el resultado de esta enfermedad. El objetivo es presentar la experiencia en nuestro Centro de pacientes con AMM/HHCI, de origen adquirido y por un error congénito del metabolismo de la cobalamina. Se presentan 27 pacientes definidos con AMM/HHCI según manifestaciones clínicas, hallazgos bioquímicos y moleculares, datos nutricionales maternos, tratamiento y evolución. Para este estudio retrospectivo (2005-2022) se recogieron datos de las historias clínicas de los pacientes estudiados en nuestro Centro. Ácido metilmalónico urinario y homocisteína plasmática se determinaron por técnicas cromatográficas en 100% de los pacientes; aminoácidos plasmáticos, vitamina-B12 y acilcarnitinas en la mayoría de ellos. Estudios en los genes MMACHC y MMADHC en 6 y 2 pacientes, respectivamente; en 4 se realizó secuenciación de nueva generación. Las manifestaciones neurológicas predominaron como síntomas de presentación (59%, 16/27), seguidas de síntomas hematológicos 52% (14/27) y dificultades de alimentación 48% (13/27). Veintidos pacientes recibieron terapia específica y el 59% (16/27) revirtió rápidamente los síntomas. El estudio del gen MMACHC permitió identificar 4 pacientes con la variante c.271dupA. A través de un algoritmo diagnóstico diferencial se pudieron clasificar 6 pacientes con un error innato del metabolismo y 16 pacientes con una forma adquirida (déficit nutricional materno). El diagnóstico y tratamiento precoz de AMM/HHCI, aun cuando sean causados por deficiencia de cofactores, puede favorecer el pronóstico neurológico de los pacientes. . Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2022-10-26 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto . https://revistas.unc.edu.ar/index.php/med/article/view/39089 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 79 No. Suplemento JIC XXIII (2022): Suplemento JIC XXIII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 79 Núm. Suplemento JIC XXIII (2022): Suplemento JIC XXIII Revista da Faculdade de Ciências Médicas de Córdoba; v. 79 n. Suplemento JIC XXIII (2022): Suplemento JIC XXIII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0 |