title: First two unrelated cases of isolated sedoheptulokinase deficiency: A benign disorder?
abstract: We present the first two reported unrelated patients with an isolated sedoheptulokinase (SHPK) deficiency. The first patient presented with neonatal cholestasis, hypoglycemia, and anemia, while the second patient presented with congenital arthrogryposis multiplex, multiple contractures, and dysmorphisms. Both patients had elevated excretion of erythritol and sedoheptulose, and each had a homozygous nonsense mutation in SHPK. SHPK is an enzyme that phosphorylates sedoheptulose to sedoheptulose-7-phosphate, which is an important intermediate of the pentose phosphate pathway. It is questionable whether SHPK deficiency is a causal factor for the clinical phenotypes of our patients. This study illustrates the necessity of extensive functional and clinical workup for interpreting a novel variant, including nonsense variants.
authors: Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands, m.wamelink@vumc.nl.
authors: Mirjam M C
authors: MM
authors: Wamelink
authors: Ruben J J F
authors: RJ
authors: Ramos
authors: Annette P M
authors: AP
authors: van den Elzen
authors: George J G
authors: GJ
authors: Ruijter
authors: Ramon
authors: R
authors: Bonte
authors: Luisa
authors: L
authors: Diogo
authors: Paula
authors: P
authors: Garcia
authors: Nelson
authors: N
authors: Neves
authors: Benjamin
authors: B
authors: Nota
authors: Arvand
authors: A
authors: Haschemi
authors: Isabel
authors: I
authors: Tavares de Almeida
authors: Gajja S
authors: GS
authors: Salomons
mesh_terms: D000740:Anemia / Q000150:complications / Q000235:genetics; D001176:Arthrogryposis / Q000235:genetics; D002675:Child, Preschool; D002779:Cholestasis / Q000150:complications / Q000235:genetics; D018389:Codon, Nonsense; D003241:Consanguinity; D005260:Female; D006539:Heptoses / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000150:complications / Q000235:genetics; D008297:Male; D010427:Pentose Phosphate Pathway / Q000235:genetics*; D010641:Phenotype; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency* / Q000235:genetics*; D013403:Sugar Phosphates / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D006539:Heptoses; D013403:Sugar Phosphates; D014157:Transcription Factors; C020495:sedoheptulose 7-phosphate; C003011:sedoheptulose; D017853:Phosphotransferases (Alcohol Group Acceptor); C404793:SHPK protein, human
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