Novel mutation of PPOX gene in a patient with abdominal pain and syndrome of inappropriate antidiuresis

Isabella Tabaro, Giuseppe Reimondo, Giangiacomo Osella, Caterina Aurizi, Pasquale Caraci, Luca Barbieri, Daniela Francesca Giachino, Fabio Sirchia, Massimo Terzolo

Research output: Contribution to journalArticle

Abstract

PURPOSE: Acute porphyrias are metabolic disorders of heme biosynthesis characterized by acute life-threatening attacks. The diagnosis is often missed since clinical presentation is aspecific mimicking other medical and surgical conditions. Variegate porphyria (VP) is an autosomal dominant inherited disease with incomplete penetrance due to decreased activity of the Protoporphyrinogen Oxydase (PPOX) gene; most VP mutations are family specific. We report the case of a 40 year-old woman who presented many times to the emergency department complaining of unexplained abdominal pain and laboratory investigations showed repeatedly hyponatremia. Syndrome of inappropriate antidiuresis (SIAD) was confirmed and measurement of urine porphobilinogen and delta-aminolevulinic acid disclosed the diagnosis of acute porphyria. The genetic analysis of PPOX gene was performed.

METHODS: The entire coding sequence and exon/intron boundaries of PPOX gene were amplified in 5 different Polymerase Chain Reaction (PCR) fragments. In silico prediction of the pathogenicity of the mutation was determined by using different tools, Polyphen2, SNPs&GO, SNPs3D.

RESULTS: The genetic analysis of PPOX gene revealed a novel missense variant c.1376 G > A (p.Cys459Tyr) in heterozygous state. The same variant was later found in one of her cousins with skin lesions and other three younger asymptomatic relatives. We provided evidence that this novel mutation is likely to be pathogenetic.

CONCLUSIONS: Our case highlights the importance of considering VP in the differential diagnosis of SIAD and underlines the role of genetic screening in the management of such patients. The finding of a novel mutation of PPOX gene in our index case has allowed to recognize an affected family.

Original languageEnglish
Pages (from-to)403-406
Number of pages4
JournalEndocrine
Volume61
Issue number3
DOIs
Publication statusPublished - Sep 2018

Fingerprint

Variegate Porphyria
Abdominal Pain
Mutation
Acute Intermittent Porphyria
Genes
Porphobilinogen
Aminolevulinic Acid
Penetrance
Hyponatremia
Genetic Testing
Heme
Computer Simulation
Introns
Single Nucleotide Polymorphism
Virulence
Hospital Emergency Service
Exons
Differential Diagnosis
protoporphyrinogen
Urine

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Novel mutation of PPOX gene in a patient with abdominal pain and syndrome of inappropriate antidiuresis. / Tabaro, Isabella; Reimondo, Giuseppe; Osella, Giangiacomo; Aurizi, Caterina; Caraci, Pasquale; Barbieri, Luca; Giachino, Daniela Francesca; Sirchia, Fabio; Terzolo, Massimo.

In: Endocrine, Vol. 61, No. 3, 09.2018, p. 403-406.

Research output: Contribution to journalArticle

Tabaro, I, Reimondo, G, Osella, G, Aurizi, C, Caraci, P, Barbieri, L, Giachino, DF, Sirchia, F & Terzolo, M 2018, 'Novel mutation of PPOX gene in a patient with abdominal pain and syndrome of inappropriate antidiuresis', Endocrine, vol. 61, no. 3, pp. 403-406. https://doi.org/10.1007/s12020-018-1569-5
Tabaro, Isabella ; Reimondo, Giuseppe ; Osella, Giangiacomo ; Aurizi, Caterina ; Caraci, Pasquale ; Barbieri, Luca ; Giachino, Daniela Francesca ; Sirchia, Fabio ; Terzolo, Massimo. / Novel mutation of PPOX gene in a patient with abdominal pain and syndrome of inappropriate antidiuresis. In: Endocrine. 2018 ; Vol. 61, No. 3. pp. 403-406.
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T1 - Novel mutation of PPOX gene in a patient with abdominal pain and syndrome of inappropriate antidiuresis

AU - Tabaro, Isabella

AU - Reimondo, Giuseppe

AU - Osella, Giangiacomo

AU - Aurizi, Caterina

AU - Caraci, Pasquale

AU - Barbieri, Luca

AU - Giachino, Daniela Francesca

AU - Sirchia, Fabio

AU - Terzolo, Massimo

PY - 2018/9

Y1 - 2018/9

N2 - PURPOSE: Acute porphyrias are metabolic disorders of heme biosynthesis characterized by acute life-threatening attacks. The diagnosis is often missed since clinical presentation is aspecific mimicking other medical and surgical conditions. Variegate porphyria (VP) is an autosomal dominant inherited disease with incomplete penetrance due to decreased activity of the Protoporphyrinogen Oxydase (PPOX) gene; most VP mutations are family specific. We report the case of a 40 year-old woman who presented many times to the emergency department complaining of unexplained abdominal pain and laboratory investigations showed repeatedly hyponatremia. Syndrome of inappropriate antidiuresis (SIAD) was confirmed and measurement of urine porphobilinogen and delta-aminolevulinic acid disclosed the diagnosis of acute porphyria. The genetic analysis of PPOX gene was performed.METHODS: The entire coding sequence and exon/intron boundaries of PPOX gene were amplified in 5 different Polymerase Chain Reaction (PCR) fragments. In silico prediction of the pathogenicity of the mutation was determined by using different tools, Polyphen2, SNPs&GO, SNPs3D.RESULTS: The genetic analysis of PPOX gene revealed a novel missense variant c.1376 G > A (p.Cys459Tyr) in heterozygous state. The same variant was later found in one of her cousins with skin lesions and other three younger asymptomatic relatives. We provided evidence that this novel mutation is likely to be pathogenetic.CONCLUSIONS: Our case highlights the importance of considering VP in the differential diagnosis of SIAD and underlines the role of genetic screening in the management of such patients. The finding of a novel mutation of PPOX gene in our index case has allowed to recognize an affected family.

AB - PURPOSE: Acute porphyrias are metabolic disorders of heme biosynthesis characterized by acute life-threatening attacks. The diagnosis is often missed since clinical presentation is aspecific mimicking other medical and surgical conditions. Variegate porphyria (VP) is an autosomal dominant inherited disease with incomplete penetrance due to decreased activity of the Protoporphyrinogen Oxydase (PPOX) gene; most VP mutations are family specific. We report the case of a 40 year-old woman who presented many times to the emergency department complaining of unexplained abdominal pain and laboratory investigations showed repeatedly hyponatremia. Syndrome of inappropriate antidiuresis (SIAD) was confirmed and measurement of urine porphobilinogen and delta-aminolevulinic acid disclosed the diagnosis of acute porphyria. The genetic analysis of PPOX gene was performed.METHODS: The entire coding sequence and exon/intron boundaries of PPOX gene were amplified in 5 different Polymerase Chain Reaction (PCR) fragments. In silico prediction of the pathogenicity of the mutation was determined by using different tools, Polyphen2, SNPs&GO, SNPs3D.RESULTS: The genetic analysis of PPOX gene revealed a novel missense variant c.1376 G > A (p.Cys459Tyr) in heterozygous state. The same variant was later found in one of her cousins with skin lesions and other three younger asymptomatic relatives. We provided evidence that this novel mutation is likely to be pathogenetic.CONCLUSIONS: Our case highlights the importance of considering VP in the differential diagnosis of SIAD and underlines the role of genetic screening in the management of such patients. The finding of a novel mutation of PPOX gene in our index case has allowed to recognize an affected family.

U2 - 10.1007/s12020-018-1569-5

DO - 10.1007/s12020-018-1569-5

M3 - Article

C2 - 29516370

VL - 61

SP - 403

EP - 406

JO - Endocrine

JF - Endocrine

SN - 1355-008X

IS - 3

ER -