Recently, the plasma cytokines FGF‐21 and GDF‐15 were described as cellular metabolic regulators. They share an endocrine function and are highly expressed in the liver under stress and during starvation. Several studies found that these markers have high sensitivity and specificity for the diagnosis of mitochondrial diseases, especially those with prominent muscular involvement. In our study, we aimed to determine whether these markers could help distinguish mitochondrial diseases from other groups of inherited diseases. We measured plasma FGF‐21 and GDF‐15 concentrations in 122 patients with genetically confirmed primary mitochondrial disease and 127 patients with non‐mitochondrial inherited diseases. Although GDF‐15 showed better analytical characteristics (sensitivity = 0.66, specificity = 0.64, area under the curve [AUC] = 0.88) compared to FGF‐21 (sensitivity = 0.51, specificity = 0.76, AUC = 0.78) in the pediatric group of mitochondrial diseases, both markers were also elevated in a variety of non‐mitochondrial diseases, especially those with liver involvement (Gaucher disease, galactosemia, glycogenosis types 1a, 1b, 9), organic acidurias and some leukodystrophies. Thus, the overall positive and negative predictive values were not acceptable for these measurements to be used as diagnostic tests for mitochondrial diseases (FGF‐21 positive predictive value [PPV] = 34%, negative predictive value [NPV] = 73%; GDF‐15 PPV = 47%, NPV = 28%). We suggest that FGF‐21 and GDF‐15 increase in patients with metabolic diseases with metabolic or oxidative stress and inflammation.

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Background: Meier-Gorlin syndrome (MGS) is a rare genetic syndrome inherited in an autosomal dominant or autosomal recessive manner. The disorder is characterized by bilateral microtia, absence or hypoplasia of the patella, and an intrauterine growth retardation as well as a number of other characteristic features. The cause of the disease is mutations in genes encoding proteins involved in the regulation of the cell cycle (ORC1,

Type I-IV proximal spinal muscular atrophy (SMA) is one of the most common autosomal reces sive diseases, which are characterized in the majority of cases by a severely disabling course. Proximal SMA results from mutations in the telomeric copy of SMN1 gene. Major SMN1 gene mutation types are deletions in the exons 7 and/or 8, which were revealed to be in the homozygous state in 95% of patients. Deletions in the indicated exons of SMN1 gene were revealed in a compound heterozygous state in combination with intragenic point mutations in the remainder 5% of proximal SMA cases. In the present study, we performed an analysis of point mutations in eight patients with type I-III proximal SMA phenotype, which had a dele tion in 7-8 exons of SMN1 gene in the heterozygous state. We revealed seven different mutations, two of which (c.824G>C (p.Gly275Ala) and c.825 2A>T) are described here for the first time. In addition, mutation c.824G>C (p.Gly275Ala) was observed twice in the examined sample. In seven cases a heterozygous carrier of point mutations was one of the parents of the affected children (in six cases, the father; in one case, the mother). Only one mutation, c.43C>T (p.Gln15X), emerged de novo in a generative cell or male cell of the child's father.

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