Author/Editor		Meglič, Anamarija; Debeljak, Maruša; Kovač, Jernej; Trampuš-Bakija, Alenka; Rajić, Vladan; Kojc, Nika; Trebušak Podkrajšek, Katarina
Title		SPTB related spherocytosis in a three-generation family presenting with kidney failure in adulthood due to co-occurrence of UMOD disease causing variant
Type		članek
Publication year		2020
Volume		str. str.
ISSN		0211-6995 - Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia
Language		eng
Abstract		Background: Hereditary spherocytosis is clinically and genetically heterogeneous disorderand its clinical characteristics are spherocytosis, anaemia, jaundice and splenomegaly. Theaetiology is associated to the genes encoding proteins involved in the interaction betweenthe erythrocyte membrane and the lipid bilayer. Causative variants in [beta]I-spectrin (SPTB) genepresenting as mild to moderately severe disease are responsible for approximately 25% casesin the USA and Europe. Among kidney disease, isolated cases of nephrotic syndrome due tomembranoproliferative glomerulonephritis and macroscopic haematuria with proteinuriadue to IgA nephropathy were previously reported in patients with SPTB deficiency.Objective: Seven patients from the same family with spherocytosis were evaluated to assessthe kidney failure presented in all affected adult patients.Methods: Clinical, radiological and laboratory investigations were issued to evaluate thespherocytosis and kidney disease. In selected patients, we also performed genetics test-ing with next generation sequencing of genes related to hereditary spherocytosis, inheritedglomerular disorders and tubulo-interstitial kidney disease.Results: Among the family members with spherocytosis, two adults had end-stage kidneydisease and one chronic kidney disease stage 4 with unspecific histopathological findingsof interstitial fibrosis/tubular atrophy and glomerulosclerosis. At the time, there were nosigns of kidney disease present in four paediatric patients. Novel nonsense variant in SPTB gene (NM 001024858; c.4796G>A; p.Trp1599Ter) was detected in all family members withspherocytosis and was predicted to be disease causing. Furthermore, all adult patients withkidney failure and two paediatric cousins of the index patients were heterozygous for theUMOD gene variant (NM 003361.3:c.552G>C, NP 003352.2:p.Trp184Cys) previously reportedin patients with tubulo-interstitial kidney disease. UMOD variant was not present in theindex patients.Conclusions: The co-occurrence of any two rare inherited disorders is extremely rare, whileto our knowledge the co-occurrence of genetically confirmed HS and autosomal dominanttubulo-interstitial kidney disease (ADTKD) has previously not been reported. It is not possi-bly to evaluate whether the haemolytic crises due to HS are influencing the progression ofthe UMOD related renal disease, since the UMOD related ADTKD characteristics in generaland in here presented family are extremely variable. Nevertheless, the observed kidney dis-ease in the family is warranting the regular nephrological examinations in UMOD positivepaediatric patients in the family in order to recognise hyperuricemia and treat it as earlyas possible. This is emphasising the importance of serum uric acid detection in routinelaboratory screening of paediatric patients in order to identify early signs of tubular injuryindicating possible ADTKD.
Keywords		hereditary spherocytosis tubulo-interstitial kidney disease chronic kidney disease dedna sferocitoza tubulo-intersticijska bolezen ledvic kronična bolezen ledvic