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...
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| 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 |
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| Sumario: | 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. |
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