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Erschienen in:
09.05.2015 | Clinical Quiz
Congenital nephrotic syndrome with dysmorphic features and death in early infancy: Answers
Erschienen in: Pediatric Nephrology | Ausgabe 8/2016
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1.
Congenital nephrotic syndrome (CNS) is usually caused by genetic defects affecting the glomerular filter. The most common defects are nephrin mutations whereas defective WT1, PLCE1, LAMB2, or NPHS2 gene products are less common [1, 2]. Additionally, CNS has been described in association with metabolic diseases, such as respiratory chain deficiency [3]. Variants in integrin α3 (ITGA3) are known to cause lung disease in combination with nephrotic syndrome [4]. The most common non-genetic causes are infectious diseases, such as cytomegalovirus infection [5, 6] and congenital syphilis [7].
CNS can also occur in congenital disorders of glycosylation (CDG). So far, it has been described in the subtypes PMM2-CDG, ALG1-CDG, and various cases of CDG-x, i.e., cases in which the subtype has not been identified.
Taking the dysmorphic and multiorgan presentation of the described patient into account, the differential diagnosis in the presented case consists of mitochondrial cytopathy, CDG, and ITGA3 disease. The most likely option with regards to the typical dysmorphic presentation, i.e., inverted nipples and facial dysmorphisms, is CDG.
2.
The analysis of serum transferrin is the primary diagnostic tool for cases with suspicion of CDG. This group of diseases affects the glycosylation process and is known to cause a great variety of symptoms in almost all organ systems. There are two distinct pathologic patterns: the type 1 pattern with a decreased tetrasialo-fraction and increased di- and asialo-transferrin fractions, and the type 2 pattern, which shows an additional increase in the mono- and/or trisialo-transferrin bands [8].
Having obtained a pathological transferrin test, genetic analysis of the genes associated with CNS in CDG should be initiated. If this leads to no result, whole-exome sequencing is another option, which may facilitate the identification of the causative gene. However, this method has limitations, especially in consanguineous families where a vast number of variants and mutations is not unusual.