BACKGROUND: Phosphomannomutase 2 deficiency (PMM2-CDG) affects glycosylation pathways such as the N-glycosylation pathway, resulting in loss of function of multiple proteins. This disorder causes multisystem involvement with a high variability among patients. PMM2-CDG is an autosomal recessive disorder, which can be caused by inheriting two pathogenic variants, de novo mutations or uniparental disomy.
METHODS: Our patient presented with multisystem symptoms at an early age including developmental delay, ataxia, and seizures. No diagnosis was obtained till the age of 31 years, when genetic testing was reinitiated. The patient was diagnosed with a complete maternal mixed hetero/isodisomy of chromosome 16, with a homozygous pathogenic PMM2 variant (p.Phe119Leu) causing PMM2-CDG.A literature review revealed eight cases of uniparental disomy as an underlying cause of CDG, four of which are PMM2-CDG.
CONCLUSIONS: Since the incidence of homozygosity for PMM2 variants is rare, we suggest further investigations for every homozygous PMM2-CDG patient where the segregation does not fit. These investigations include testing for UPD or a deletion in one of the two alleles, as this will have an impact on recurrence risk in genetic counseling.

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) has recently been established. Herein we report the sixth case of ACD-associated RCC with a sarcomatoid change. The patient was a 77-year-old man who regularly underwent hemodialysis for 14 years due to chronic renal failure resulting from IgA nephropathy. On computed tomography, a large right RCC was observed with contrast enhancement in the arterial phase. A nodular protrusion into the perirenal fat was detected. Right nephrectomy was performed under laparoscopy. Surgically resected specimens revealed a tan-to-yellow tumor (95 × 75 × 55 mm) with a whitish nodule (20 × 15 × 15 mm) invading into the perirenal fat. Histopathologically, the large carcinoma component of the tumor displayed a cribriform or microcystic growth pattern with deposition of oxalate crystals. The whitish nodule corresponded to the sarcomatoid component, and the spindled and pleomorphic tumor cells showed diffuse positivity of p53 on immunohistochemistry. Fluorescence in situ hybridization revealed trisomy of chromosomes 3 and 16 in the carcinoma component, as was expected from the literature. In addition, increased polysomy of these chromosomes was also observed in the sarcomatoid component. This finding may be related to the development of the sarcomatoid component along with the TP53 mutation.