scholarly journals Homozygous Missense Mutation on Exon 22 of PKHD1 Gene Causing Fatal Autosomal Recessive Polycystic Kidney Disease

2021 ◽  
Vol 11 (01) ◽  
pp. e70-e73
Author(s):  
Sajina Sathyan ◽  
Femitha Pournami ◽  
Gopala Krishna Madhavilatha ◽  
Amrit Tuteja ◽  
Anand Nandakumar ◽  
...  
Keyword(s):  
Renal Failure ◽  
Respiratory Failure ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Pulmonary Hypoplasia ◽  
Missense Variant ◽  
Diagnostic Techniques ◽  
Polycystic Kidney ◽  
End Stage

AbstractAutosomal recessive polycystic kidney disease, described as a congenital hepatorenal fibrocystic syndrome, is a significant inherited cause of end stage renal failure in children with reported incidence of 1 in 20,000 live births. The clinical spectrum is wide. Antenatal findings of echogenic reniform enlarged kidneys associated with evidence of intrauterine renal failure in the form of severe oligoamnios are pathognomonic. Postnatal illness ranges from fatal respiratory failure due to pulmonary hypoplasia in neonates to chronic kidney disease in children, or later presentation of ductal plate malformation and portal hypertension. Advances in genetic diagnostic techniques have allowed recognition of genotypes. We report a novel homozygous missense variant on exon 22 of PKHD1 gene (chr6:51915067G > A; c.2167C > T) that results in the amino acid substitution of cysteine for arginine at codon 723 (p.Arg723Cys). The affected neonate presented with antenatal anhydramnios, classical radiological features, and severe hypoxic respiratory failure likely due to pulmonary hypoplasia and succumbed. The parents were found to be heterozygous carriers. Detection of the specific variant in the proband facilitated prenatal investigation in the next pregnancy.

scholarly journals Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease

2021 ◽  
Vol 22 (12) ◽  
pp. 6523
Author(s):  
Adrian Cordido ◽  
Marta Vizoso-Gonzalez ◽  
Miguel A. Garcia-Gonzalez
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Molecular Basis ◽  
Autosomal Recessive ◽  
Polycystic Kidney ◽  
Phenotypic Spectrum ◽  
New Gene ◽  
Stage Renal Disease ◽  
End Stage ◽  
Molecular Pathophysiology

Autosomal recessive polycystic kidney disease (ARPKD) is a rare disorder and one of the most severe forms of polycystic kidney disease, leading to end-stage renal disease (ESRD) in childhood. PKHD1 is the gene that is responsible for the vast majority of ARPKD. However, some cases have been related to a new gene that was recently identified (DZIP1L gene), as well as several ciliary genes that can mimic a ARPKD-like phenotypic spectrum. In addition, a number of molecular pathways involved in the ARPKD pathogenesis and progression were elucidated using cellular and animal models. However, the function of the ARPKD proteins and the molecular mechanism of the disease currently remain incompletely understood. Here, we review the clinics, treatment, genetics, and molecular basis of ARPKD, highlighting the most recent findings in the field.

scholarly journals Autosomal recessive polycystic kidney disease: case report of a newborn with rare PKHD1 mutation, rapid renal enlargement and early fatal outcome

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Gregorio Serra ◽  
Giovanni Corsello ◽  
Vincenzo Antona ◽  
Maria Michela D’Alessandro ◽  
Nicola Cassata ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Fatal Outcome ◽  
Pulmonary Insufficiency ◽  
Homozygous Mutation ◽  
Polycystic Kidney ◽  
Disease Case ◽  
Renal Enlargement

Abstract Introduction Autosomal recessive polycystic kidney disease (ARPKD; MIM#263200) is one of the most frequent pediatric renal cystic diseases, with an incidence of 1:20,000. It is caused by mutations of the PKHD1 gene, on chromosome 6p12. The clinical spectrum is highly variable, ranging from late-onset milder forms to severe perinatal manifestations. The management of newborns with severe pulmonary insufficiency is challenging, and causes of early death are sepsis or respiratory failure. In cases of massive renal enlargement, early bilateral nephrectomy and peritoneal dialysis may reduce infant mortality. However, there is no conclusive data on the role of surgery, and decision-making is driven by patient’s clinical condition and expertise of the center. Patient presentation We hereby describe a preterm female newborn with perinatal, rapid and bilateral, abnormal growth of both kidneys, respiratory failure and initial signs of liver disease. She was subsequently confirmed to be affected by a rare and severe homozygous mutation of the PKHD1 gene, inherited from both her consanguineous parents. Our patient died 78 days after birth, due to a fungal sepsis which worsened her respiratory insufficiency. Conclusions This patient report shows some of the clinical and ethical issues of neonatal ARPKD, and the need of multidisciplinary approach and good communication with the family. Target next generation sequencing (NGS) techniques may guide and support clinicians, as well as guarantee to these patients the most appropriate clinical management, avoiding unnecessary and/or disproportionate treatments.

scholarly journals Autosomal recessive polycystic kidney disease: case report of a newborn with rare PKHD1 mutation, rapid renal enlargement and early fatal outcome

2020 ◽  
Author(s):  
Gregorio Serra ◽  
Giovanni Corsello ◽  
Vincenzo Antona ◽  
Maria Michela D'Alessandro ◽  
Nicola Cassata ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Fatal Outcome ◽  
Pulmonary Insufficiency ◽  
Homozygous Mutation ◽  
Polycystic Kidney ◽  
Disease Case ◽  
Renal Enlargement

Abstract Introduction Autosomal recessive polycystic kidney disease (ARPKD; MIM#263200) is one of the most frequent pediatric renal cystic diseases, with an incidence of 1:20,000. It is caused by mutations of the PKHD1 gene, on chromosome 6p12. The clinical spectrum is highly variable, ranging from late-onset milder forms to severe perinatal manifestations. The management of newborns with severe pulmonary insufficiency is challenging, and causes of early death are sepsis or respiratory failure. In cases of massive renal enlargement, early bilateral nephrectomy and peritoneal dialysis may reduce infant mortality. However, there is no conclusive data on the role of surgery, and decision-making is driven by patient’s clinical condition and expertise of the center. Patient presentation We hereby describe a preterm female newborn with perinatal, rapid and bilateral, abnormal growth of both kidneys, respiratory failure and initial signs of liver disease. She was subsequently confirmed to be affected by a rare and severe homozygous mutation of the PKHD1 gene, inherited from both her consanguineous parents. Our patient died 78 days after birth, due to a fungal sepsis which worsened her respiratory insufficiency. Conclusions This patient report shows some of the clinical and ethical issues of neonatal ARPKD, and the need of multidisciplinary approach and good communication with the family. Target next generation sequencing (NGS) techniques may guide and support clinicians, as well as guarantee to these patients the most appropriate clinical management, avoiding unnecessary and/or disproportionate treatments.

scholarly journals The effect of uninephrectomy on progression of renal failure in autosomal dominant polycystic kidney disease.

1992 ◽  
Vol 3 (5) ◽  
pp. 1119-1123
Author(s):  
M Zeier ◽  
S Geberth ◽  
A Gonzalo ◽  
D Chauveau ◽  
J P Grünfeld ◽  
...  
Keyword(s):  
Renal Failure ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
End Stage Renal Failure ◽  
Significant Difference ◽  
Autosomal Dominant Polycystic Kidney ◽  
End Stage

The evolution of renal failure was compared in 47 patients (21 male, 26 female) with autosomal dominant polycystic kidney disease (ADPKD) in Germany, France, Spain, and Portugal who had undergone uninephrectomy (UNX) (median age at uninephrectomy, 41 yr; range, 22 to 54) and 47 non-UNX matched controls. UNX was usually performed because of uncontrolled urinary tract infection (N = 30), stones (N = 8), trauma (N = 2), or hemorrhage (N = 7). Median serum creatinine at UNX was 2.1 mg/dL (0.9 to 4.3). Twenty-eight of the 47 uninephrectomized patients progressed to end-stage renal failure. When the age at renal death was evaluated by survival analysis, only minor and nonsignificant acceleration was seen in the uninephrectomized patients (median, 50 yr; p25 = 43.6 yr; p75 = 58.3 yr, where p is the percentile) compared with non-UNX patients matched for age, sex, and serum creatinine at the time of UNX in the propositus (51.2 yr; p25 = 48.6 yr; p75 = 56.1 yr). In addition, the median interval for serum creatinine to rise from 4 to 8 mg/dL was similar in UNX (21.3 months) versus nonuninephrectomized ADPKD patients (21.9 months). Renal survival differed in the two genders. In females, no significant difference of age at renal death was found between UNX (median age, 51.6 yr) and non-UNX ADPKD patients (53.7 yr). In male UNX patients, age at renal death was slightly (but not significantly) less than in non-UNX patients (median age, 47.3 versus 52.7 yr). All male patients reaching end-stage renal failure before age 44 were severely hypertensive.

scholarly journals Autosomal recessive polycystic kidney disease: case report of a newborn with rare PKHD1 mutation, rapid renal enlargement and early fatal outcome

2020 ◽  
Author(s):  
Gregorio Serra ◽  
Giovanni Corsello ◽  
Vincenzo Antona ◽  
Maria Michela D'Alessandro ◽  
Nicola Cassata ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Fatal Outcome ◽  
Pulmonary Insufficiency ◽  
Homozygous Mutation ◽  
Polycystic Kidney ◽  
Disease Case ◽  
Renal Enlargement

Abstract Introduction: Autosomal recessive polycystic kidney disease (ARPKD; MIM#263200) is one of the most frequent pediatric renal cystic diseases, with an incidence of 1:20,000. It is caused by mutations of the PKHD1 gene, on chromosome 6p12. The clinical spectrum is highly variable, ranging from late-onset milder forms to severe perinatal manifestations. The management of newborns with severe pulmonary insufficiency is challenging, and causes of early death are sepsis or respiratory failure. In cases of massive renal enlargement, early bilateral nephrectomy and peritoneal dialysis may reduce infant mortality. However, there is no conclusive data on the role of surgery, and decision-making is driven by patient’s clinical condition and expertise of the center. Patient presentation: We hereby describe a preterm female newborn with perinatal, rapid and bilateral, abnormal growth of both kidneys, respiratory failure and initial signs of liver disease. She was subsequently confirmed to be affected by a rare and severe homozygous mutation of the PKHD1 gene, inherited from both her consanguineous parents. Our patient died 78 days after birth, due to a fungal sepsis which worsened her respiratory insufficiency. Conclusions: This patient report shows some of the clinical and ethical issues of neonatal ARPKD, and the need of multidisciplinary approach and good communication with the family. Target next generation sequencing (NGS) techniques may guide and support clinicians, as well as guarantee to these patients the most appropriate clinical management, avoiding unnecessary and/or disproportionate treatments.

Polycystic kidney disease

2020 ◽  
Vol 13 (6) ◽  
pp. 326-335
Author(s):  
Soo Oh ◽  
Rabeet Khan ◽  
Ahmed Ziada
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Antenatal Screening ◽  
Polycystic Kidney ◽  
Holistic Management ◽  
Key Points ◽  
Common Causes ◽  
End Stage

Polycystic kidney disease (PKD) is a monogenic, hereditary disorder of the kidneys that leads to fluid-filled cysts within the renal tubes. It is one of the most common causes of end-stage renal failure. There are two types, the more common autosomal dominant (ADPKD) and the rarer autosomal recessive (ARPKD). ADPKD mostly presents in adulthood, whereas ARPKD is usually detected during antenatal screening or as a neonate. This article will focus on key points to understand and consider for the holistic management of PKD.

Sign in / Sign up

Export Citation Format

Share Document