TY - JOUR
T1 - Heterogenous clinical landscape in a consanguineous malonic aciduria family
AU - Snanoudj, Sarah
AU - Torre, Stéphanie
AU - Sudrié-Arnaud, B. nédicte
AU - Abily-Donval, Lenaig
AU - Goldenberg, Alice
AU - Salomons, Gajja S.
AU - Marret, Stéphane
AU - Bekri, Soumeya
AU - Tebani, Abdellah
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Malonic aciduria is an extremely rare inborn error of metabolism due to malonyl-CoA decarboxylase deficiency. This enzyme is encoded by the MLYCD (Malonyl-CoA Decarboxylase) gene, and the disease has an autosomal recessive inheritance. Malonic aciduria is characterized by systemic clinical involvement, including neurologic and digestive symptoms, metabolic acidosis, hypoglycemia, failure to thrive, seizures, developmental delay, and cardiomyopathy. We describe here two index cases belonging to the same family that, despite an identical genotype, present very different clinical pictures. The first case is a boy with neonatal metabolic symptoms, abnormal brain MRI, and dilated cardiomyopathy. The second case, the cousin of the first patient in a consan-guineous family, showed later symptoms, mainly with developmental delay. Both patients showed high levels of malonylcarnitine on acylcarnitine profiles and malonic acid on urinary organic acid chromatographies. The same homozygous pathogenic variant was identified, c.346C > T; p. (Gln116*). We also provide a comprehensive literature review of reported cases. A review of the literature yielded 52 cases described since 1984. The most common signs were developmental delay and cardiomyopathy. Increased levels of malonic acid and malonylcarnitine were constant. Presentations ranged from neonatal death to patients surviving past adolescence. These two cases and reported patients in the literature highlight the inter-and intrafamilial variability of malonic aciduria.
AB - Malonic aciduria is an extremely rare inborn error of metabolism due to malonyl-CoA decarboxylase deficiency. This enzyme is encoded by the MLYCD (Malonyl-CoA Decarboxylase) gene, and the disease has an autosomal recessive inheritance. Malonic aciduria is characterized by systemic clinical involvement, including neurologic and digestive symptoms, metabolic acidosis, hypoglycemia, failure to thrive, seizures, developmental delay, and cardiomyopathy. We describe here two index cases belonging to the same family that, despite an identical genotype, present very different clinical pictures. The first case is a boy with neonatal metabolic symptoms, abnormal brain MRI, and dilated cardiomyopathy. The second case, the cousin of the first patient in a consan-guineous family, showed later symptoms, mainly with developmental delay. Both patients showed high levels of malonylcarnitine on acylcarnitine profiles and malonic acid on urinary organic acid chromatographies. The same homozygous pathogenic variant was identified, c.346C > T; p. (Gln116*). We also provide a comprehensive literature review of reported cases. A review of the literature yielded 52 cases described since 1984. The most common signs were developmental delay and cardiomyopathy. Increased levels of malonic acid and malonylcarnitine were constant. Presentations ranged from neonatal death to patients surviving past adolescence. These two cases and reported patients in the literature highlight the inter-and intrafamilial variability of malonic aciduria.
KW - Beta-oxidation
KW - Cardiomyopathy
KW - Inborn errors of metabolism
KW - MLYCD
KW - malonic aciduria
UR - http://www.scopus.com/inward/record.url?scp=85119615560&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms222312633
DO - https://doi.org/10.3390/ijms222312633
M3 - Article
C2 - 34884438
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 23
M1 - 12633
ER -