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Adult-onset renal failure in a family with Alagille syndrome with proteinuria and a novel JAG1 mutation.

Hayashi N, Okuyama H, Matsui Y, Yamaya H, Kinoshita E, Minato H, Niida Y, Yokoyama H - Clin Kidney J (2013)

Bottom Line: In this family, five members of three generations had clinical features implicated in AGS.Three members had adult-onset renal dysfunction with proteinuria, and two of them required haemodialysis therapy.AGS should be considered in the differential diagnosis of proteinuric renal disease, even in adult patients.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology , Kanazawa Medical University , Uchinada, Ishikawa , Japan.

ABSTRACT
Alagille syndrome (AGS) is an autosomal-dominant multi-organ disorder involving the liver, heart, eyes, face and skeleton. In addition, various renal abnormalities have also been reported in several cases. We describe a patient with a novel frameshift mutation in exon 12 of the JAG1 gene who presented with chronic renal failure. In this family, five members of three generations had clinical features implicated in AGS. Three members had adult-onset renal dysfunction with proteinuria, and two of them required haemodialysis therapy. AGS should be considered in the differential diagnosis of proteinuric renal disease, even in adult patients.

No MeSH data available.


Related in: MedlinePlus

CT scan showing a hypoplastic right kidney and a malrotated left kidney.
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SFT027F2: CT scan showing a hypoplastic right kidney and a malrotated left kidney.

Mentions: A 47-year-old man was admitted to our hospital for treatment of end-stage renal disease (ESRD). He was born at term with a weight of 2550 g. He was diagnosed with pulmonary artery stenosis (PS) at the age of 14 years when he had an operation for atrial septal defect (ASD). He had occasionally presented with proteinuria and hypertension since high school. He underwent a liver biopsy at the age of 34 years due to a slightly elevated liver enzyme level. There was no bile duct paucity. He was later diagnosed with an alcoholic liver injury. At this time, renal dysfunction with serum creatinine level of 114.9 µmol/L was noted for the first time. Subsequently, this patient stopped attending the hospital. Two months before admission, he came to our hospital with general malaise and leg oedema, and was diagnosed with chronic renal failure of unknown origin. After admission, we started him on haemodialysis. Physical examination disclosed a characteristic triangular face, a straight nose and a pointed chin (Figure 1). A pulmonary ejection systolic murmur was heard. Additional investigations showed creatinine clearance of 0.117 mL/s. The 24-h protein excretion level was 1 g without haematuria. Although serological markers for hepatitis virus were negative, elevated levels of liver enzymes (AST, 39 U/L; ALT, 38 U/L; γGTP, 672 U/L and ALP, 1886 U/L) were found. A computed tomography (CT) scan showed hypoplastic and malrotated kidneys (Figure 2) and a vascular abnormality, namely, persistent left superior vena cava. A cervical X-ray showed butterfly vertebrae (Figure 3). Molecular genetic testing of the patient revealed deletion of a cytosine in exon 12 of the JAG1 gene (c. 1544delC, p. Thr515MetfsX49), which led to a shift in the reading frame starting at amino acid 515 and a subsequent early stop codon at position 564 (Figure 4).Fig. 1.


Adult-onset renal failure in a family with Alagille syndrome with proteinuria and a novel JAG1 mutation.

Hayashi N, Okuyama H, Matsui Y, Yamaya H, Kinoshita E, Minato H, Niida Y, Yokoyama H - Clin Kidney J (2013)

CT scan showing a hypoplastic right kidney and a malrotated left kidney.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400474&req=5

SFT027F2: CT scan showing a hypoplastic right kidney and a malrotated left kidney.
Mentions: A 47-year-old man was admitted to our hospital for treatment of end-stage renal disease (ESRD). He was born at term with a weight of 2550 g. He was diagnosed with pulmonary artery stenosis (PS) at the age of 14 years when he had an operation for atrial septal defect (ASD). He had occasionally presented with proteinuria and hypertension since high school. He underwent a liver biopsy at the age of 34 years due to a slightly elevated liver enzyme level. There was no bile duct paucity. He was later diagnosed with an alcoholic liver injury. At this time, renal dysfunction with serum creatinine level of 114.9 µmol/L was noted for the first time. Subsequently, this patient stopped attending the hospital. Two months before admission, he came to our hospital with general malaise and leg oedema, and was diagnosed with chronic renal failure of unknown origin. After admission, we started him on haemodialysis. Physical examination disclosed a characteristic triangular face, a straight nose and a pointed chin (Figure 1). A pulmonary ejection systolic murmur was heard. Additional investigations showed creatinine clearance of 0.117 mL/s. The 24-h protein excretion level was 1 g without haematuria. Although serological markers for hepatitis virus were negative, elevated levels of liver enzymes (AST, 39 U/L; ALT, 38 U/L; γGTP, 672 U/L and ALP, 1886 U/L) were found. A computed tomography (CT) scan showed hypoplastic and malrotated kidneys (Figure 2) and a vascular abnormality, namely, persistent left superior vena cava. A cervical X-ray showed butterfly vertebrae (Figure 3). Molecular genetic testing of the patient revealed deletion of a cytosine in exon 12 of the JAG1 gene (c. 1544delC, p. Thr515MetfsX49), which led to a shift in the reading frame starting at amino acid 515 and a subsequent early stop codon at position 564 (Figure 4).Fig. 1.

Bottom Line: In this family, five members of three generations had clinical features implicated in AGS.Three members had adult-onset renal dysfunction with proteinuria, and two of them required haemodialysis therapy.AGS should be considered in the differential diagnosis of proteinuric renal disease, even in adult patients.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology , Kanazawa Medical University , Uchinada, Ishikawa , Japan.

ABSTRACT
Alagille syndrome (AGS) is an autosomal-dominant multi-organ disorder involving the liver, heart, eyes, face and skeleton. In addition, various renal abnormalities have also been reported in several cases. We describe a patient with a novel frameshift mutation in exon 12 of the JAG1 gene who presented with chronic renal failure. In this family, five members of three generations had clinical features implicated in AGS. Three members had adult-onset renal dysfunction with proteinuria, and two of them required haemodialysis therapy. AGS should be considered in the differential diagnosis of proteinuric renal disease, even in adult patients.

No MeSH data available.


Related in: MedlinePlus