Systemic Messenger RNA Therapy as a Treatment for Methylmalonic Acidemia

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Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.

We describe the use of antisense morpholino oligonucleotides (AMOs) to restore normal splicing caused by intronic molecular defects identified in methylmalonic acidemia (MMA) and propionic acidemia (PA). The three new point mutations described in deep intronic regions increase the splicing scores of pseudoexons or generate consensus binding motifs for splicing factors, such as SRp40, which favo...

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Methylmalonic acidemia

The authors provide an overview of the hereditary methylmalonic acidemias, a group of metabolic disorders with varied clinical presentations. This includes the most severe form of L-methylmalonyl-CoA mutase deficiency, termed mut(o) methylmalonic acidemia, which, together with the less severe deficiencies of L-methylmalonyl-CoA mutase, are the most common causes of methylmalonic acidemia. They ...

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Methylmalonic Acidemia.

Methylmalonic Acidemia (MMA) is an inborn error of metabolism that results in accumulation of methylmalonic acid in blood and increased excretion in urine. The effects of MMA vary from mild to life threatening and it usually presents in early infancy. Affected infants can have vomiting, dehydration, hypotonia, developmental delay and failure to thrive. The emergency treatment of the newborn wit...

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Growth hormone therapy in neonatal patients with methylmalonic acidemia.

BACKGROUND Information regarding growth hormone (GH) therapy in neonatal patients with methylmalonic academia (MMA) is lacking. We present our experience with GH therapy in neonatal patients with MMA. METHODS Four neonatal patients with mut 0 type MMA were identified through newborn screening for elevated propionylcarnitine (C3) levels. GH therapy (0.6 IU/kg/week, subcutaneously) was prescrib...

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Optic neuropathy in methylmalonic acidemia and propionic acidemia.

BACKGROUND Methylmalonic acidemia (MMA) and propionic acidemia (PA) are rare hereditary disorders of protein metabolism, manifesting early in life with ketoacidosis and encephalopathy and often resulting in chronic complications. Optic neuropathy (ON) has been increasingly recognised in both conditions, mostly through isolated case reports or small cases series. We here report the clinical feat...

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ژورنال

عنوان ژورنال: Cell Reports

سال: 2017

ISSN: 2211-1247

DOI: 10.1016/j.celrep.2017.11.081