Combination of Schaaf - Yang Syndrome with Unspecified Hyperammonemia in a Newborn: Case Study

Backround. Combined pathology of primary genetic disease and rare secondary disorders presents the most diagnostical difficulties for neonatologist. Such are atypical signs of Schaaf - Yang syndrome in newborns. Case description. The premature baby was diagnosed in utero with fingers abnormality. Genetic disorder was suspected at birth due to multiple stigmas (shortened limbs, multiple joint contractures, finger deformity, cryptorchidism). Whereas severe respiratory, hemodynamic, convulsive and motor disorders, as well as pseudobulbar syndrome were regarded as manifestations of congenital pneumonia and perinatal injury of the central nervous system. Hyperammonemia was revealed at the 2nd month of life and it was regarded as secondary condition associated with combined hereditary and perinatal pathology. Any chromosome aberrations, hereditary aminoacidopathies, organic aciduria, mitochondrial diseases were excluded via multi-stage diagnostic search using karyotyping, tandem mass-spectrometry, determination of glycine concentration ratio in cerebrospinal fluid and blood. Whole-exome sequencing of the child’s DNA revealed pathogenic variant in the MAGEL2 gene in a heterozygous state (rs770374710) at the age of 3 months. This variant leads to frameshifting and premature protein translation. There were no pathological variants in the parents, thus, the patient had de novo mutation. Since there is no etiopathogenetic therapy for this disease, the patient received only syndromic therapy. Conclusion. This case demonstrates diagnostic challenges in comorbid genetic syndrome and perinatal pathology and unspecified hyperammonemia.

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