Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heat shock protein 60 (hsp60) is a mitochondrial matrix protein involved in the folding and correct assembly of polypeptides into complex mitochondrial enzymes. Its deficiency has recently been described as the most likely primary cause of congenital lactic acidaemia with multiple mitochondrial enzyme deficiencies in a female patient. We describe a new case of a girl with a substantially decreased amount of hsp60 in cultured fibroblasts. She presented from birth with hypotonia, unusual facial features, feeding difficulties and failure to thrive. Death occurred at age 4.5 years. Biochemical findings included metabolic acidosis with lactic acidaemia, hyperammonaemia and intermittent ketosis. In contrast to the previously reported case, organic acid analysis showed an altered profile throughout her life. In agreement with this profile, various mitochondrial enzyme activities were deficient in cultured fibroblasts, including enzymes of the respiratory chain and the Krebs cycle, the pyruvate dehydrogenase complex and the mitochondrial biotindependent carboxylases. Fibroblast mitochondria showed ultrastructural abnormalities, were swollen, and were mainly localized around the nucleus. The description of a second case of multiple mitochondrial enzyme deficiencies with reduced amount of hsp60 supports the idea that hsp60 deficiency might be a more common cause of mitochondrial disease. This opens new possibilities for the diagnosis and understanding of congenital lactic acidaemia.
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PMID:A new case of multiple mitochondrial enzyme deficiencies with decreased amount of heat shock protein 60. 926 94

Biallelic mutations of the GCDH gene result in Glutaric Aciduria type 1 (GA1; OMIM #231670), an uncommon autosomal recessive inborn error caused by the deficiency of glutaryl-CoA dehydrogenase (CCDH), a mitochondrial matrix protein involved in the degradation of l-lysine, L-hydroxylysine, and L-tryptophan. The enzymatic deficiency leads to the accumulation of neurotoxins causing macrocephaly at birth, hypotonia and dystonia due to bilateral striatal injury, that evolves with aging, if untreated, to fixed dystonia and akinetic-rigid parkinsonism. In this article, we describe the results of molecular studies of 5 unrelated patients with GA1 in Southern Mexico. Mutational analysis identified 2 novel likely pathogenic GCDH variants (p.Leu130Pro and p.Gly391Val), 1 pathogenic variant that is predicted to cause a premature stop codon (p.Leu370*), and 2 previously reported pathogenic variants (p.Arg294Trp and p.Arg294Gln). The recurrence of the p.Leu130Pro variant (60% of mutant alleles) suggested a possible founder mutation effect. Our results expand the mutational spectrum in GA1 patients and support the importance of early diagnosis through newborn screening that promotes early nutritional treatment and prevents metabolic crisis.
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PMID:Characterization of novel GCDH pathogenic variants causing glutaric aciduria type 1 in the southeast of Mexico. 3178 23