Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026827 (
hypotonia
)
5,860
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn error of metabolism affecting both fatty acid and amino acid oxidation. It can manifest at any age, but riboflavin-responsiveness has mainly been described in less severely affected patients. We describe an infant with severe MADD presenting with profound
hypotonia
and hepatomegaly. Treatment with riboflavin improved his muscle strength, liver size, and biochemical markers. A homozygous mutation of
electron transfer flavoprotein dehydrogenase
(
ETFDH
) was found. His motor skills continued to progress until a fatal infection-triggered deterioration at the age of 34 months. We show changes in brain magnetic resonance imaging over the course of the disease, with profound white matter abnormalities during the deterioration phase. Aggregates of mitochondria with abnormal cristae in muscle electron microscopy were noticed already in infancy. An unusual lactate dehydrogenase (LDH) isoenzyme pattern with LDH-1 predominance was additionally observed. This case demonstrates riboflavin-responsiveness in a severely affected infant with both muscular and extramuscular involvement and further underlines the variable nature of this disease.
...
PMID:Riboflavin-Responsive Multiple Acyl-CoA Dehydrogenase Deficiency Associated with Hepatoencephalomyopathy and White Matter Signal Abnormalities on Brain MRI. 2838 38
Background:
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder characterized by a wide range of clinical features, including muscle weakness, hypoglycemia, metabolic acidosis, and multisystem dysfunctions. Loss-of-function mutations in the
electron transfer flavoprotein dehydrogenase
(
ETFDH
) gene are associated with MADD. Disease-causing synonymous variants in the
ETFDH
gene have not been reported so far.
Methods:
We reported the clinical course of a Chinese girl who was diagnosed with late-onset MADD by the whole exome sequencing. The effects of variants on mRNA splicing were analyzed through transcript analysis
in vivo
and minigene splice assay
in vitro
.
Results:
The 6-month-old girl initially showed muscle weakness, muscular
hypotonia
, mild myogenic damage, and fatty liver. The blood and urine metabolic screening by tandem mass spectrometry suggested MADD. Molecular analysis of
ETFDH
gene revealed two novel heterozygous variants, a frameshift mutation c.1812delG (p.V605Yfs
*
34) in exon 13 and a synonymous variant c.579A>G (p.E193E) in exon 5. The transcript analysis
in vivo
exhibited that the synonymous variant c.579A>G caused exon 5 skipping. The minigene splice assay
in vitro
confirmed the alteration of
ETFDH
mRNA splicing which could lead to the production of a truncated protein. Supplementation of riboflavin, carnitine and low-fat diet improved the clinical symptoms.
Conclusion:
We firstly report a rare case of MADD with a pathogenic synonymous variant in the
ETFDH
gene which highlights the importance and necessity of bioinformatic analysis and functional testing for synonymous variants when searching for causative gene mutations. The results expand the spectrum of pathogenic variants in MADD.
...
PMID:A Synonymous Variant c.579A>G in the ETFDH Gene Caused Exon Skipping in a Patient With Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency: A Case Report. 3229 71
