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Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
Perinatal onset mevalonate kinase deficiency
Laurie A Steiner1, Richard A Ehrenkranz, Steven M Peterec
1Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
Summary
Severe mevalonate kinase deficiency (MKD) can present at birth with serious multisystem complications. This rare genetic disorder, mevalonic aciduria, has a poor prognosis, often resulting in fetal or neonatal death.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Medicine
Background:
- Mevalonate kinase (MK) is crucial for cholesterol and isoprene metabolism.
- MK deficiency causes mevalonic aciduria or hyperimmunoglobulinemia D and periodic fever syndrome.
- Perinatal onset MK deficiency is rare and presents as a severe multisystem disorder.
Observation:
- A family with two siblings experiencing severe, perinatal-onset mevalonic aciduria was studied.
- One sibling exhibited dysmorphic and central nervous system issues, anemia, and cholestasis.
- Both affected infants had fatal outcomes, one in utero and one neonatally.
Findings:
- Perinatal MK deficiency involves intrauterine growth restriction, cerebral abnormalities, dysmorphic features, and skeletal issues.
- Hematologic findings include dyserythropoietic anemia and thrombocytopenia.
- Other severe manifestations include cholestatic liver disease, renal failure, sepsis-like episodes, and failure to thrive.
Implications:
- Clinical presentation can mimic severe intrauterine infections or chromosomal abnormalities, delaying diagnosis.
- Perinatal onset MK deficiency carries a very poor prognosis, with high mortality.
- Further research into autopsy findings for this condition is warranted.
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