Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a 41-year-old Moroccan woman with phosphofructokinase (PFK) deficiency who presented slowly progressive muscular weakness since childhood, without rhabdomyolysis episode or hemolytic anemia. Deltoid biopsy revealed massive glycogen storage in the majority of muscle fibers and polysaccharide deposits. PFK activity in muscle was totally absent. A novel homozygous non-sense mutation was detected in PFKM gene. Our observation suggests that juvenile-onset fixed muscle weakness may be a predominant clinical feature of PFK deficiency. Vacuolar myopathy with polyglucosan deposits remains an important morphological hallmark of this rare muscle glycogenosis.
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PMID:Juvenile-onset permanent weakness in muscle phosphofructokinase deficiency. 2236 48

Hereditary muscle-type phosphofructokinase (PFK) deficiency causing intermittent hemolytic anemia and exertional myopathy due to a single nonsense mutation in PFKM has been previously described in English Springer and American Cocker Spaniels, Whippets, and mixed breed dogs. We report here on a new missense mutation associated with PFK deficiency in Wachtelhunds. Coding regions of the PFKM gene were amplified from genomic DNA and/or cDNA reverse-transcribed from RNA of EDTA blood of PFK-deficient and clinically healthy Wachtelhunds and control dogs. The amplicons were sequenced and compared to the published canine PFKM sequence. A point mutation (c.550C>T, in the coding sequence of PFKM expressed in blood) was found in all 4 affected Wachtelhunds. This missense mutation results in an amino acid substitution of arginine (Arg) to tryptophan (Trp) at position 184 of the protein expressed in blood (p.Arg184Trp). The mutation is located within an alpha-helix, and based on the SIFT analysis, this amino acid substitution is not tolerated. Amplifying the region around this mutation and digesting the PCR fragment with the restriction enzyme MspI, produces fragments that readily differentiate between PFK-deficient, carrier, and normal animals. Furthermore, we document 2 additional upstream PFKM exons expressed in canine testis but not in blood. Despite their similar phenotypic appearance and use for hunting, Wachtelhunds and English Springer Spaniels are not thought to have common ancestors. Thus, it is not surprising that different mutations are responsible for PFK deficiency in these breeds. Knowledge of the molecular basis of PFK deficiency in Wachtelhunds provides an opportunity to screen and control the spread of this deleterious trait.
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PMID:Missense mutation in PFKM associated with muscle-type phosphofructokinase deficiency in the Wachtelhund dog. 2244 93