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

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.

Novel SCNN1A gene splicing-site mutation causing autosomal recessive pseudohypoaldosteronism type 1 (PHA1) in two Italian patients belonging to the same small town

“…Ocular involvement with enlarged meibomian glands is also described in few subjects [ 12 ]. The anamnestic data of parental consanguinity restricted in our newborn the diagnostic hypotheses to the systemic form of PHA1 [ 13 , 14 ], which was confirmed by NGS analysis. The SCNN1A gene mutation identified in the proband, not previously reported in the literature, is located in a splicing site [ 15 ].…”

Smartphone use and addiction during the coronavirus disease 2019 (COVID-19) pandemic: cohort study on 184 Italian children and adolescents

“…Pediatricians and health care professionals should be aware of such potential risks related to inappropriate use of smartphones. They should monitor, in cooperation with parents, possible associated adverse effects, in order to early recognize signs and symptoms suggestive, or at high risk, for addiction [ 46 – 48 ]. They must realize, as well, the necessary interventions to prevent and/or lower the detrimental impact of smartphone overuse on children and adolescents’ health, oriented to sustain adequate physical and psychological development as well as social relationships.…”

Jacobsen syndrome and neonatal bleeding: report on two unrelated patients

“…prenatal bleeding) [ 2 , 6 ]. Then, early and continuous management (obstetric, perinatal and neonatal), careful follow-up (pediatric cardiologist and neurologist, abdominal US to rule out pyloric stenosis and kidney and urinary tract malformations, ophthalmological, audiological and orthopedic evaluations, blood, immunological and endocrine tests, oncologic surveillance) [ 3 , 23 – 26 ], and integrated (occupational, speech, physical and behavioral therapists) home-based care, must be even more necessary for these patients [ 27 , 28 ], whose complex clinical picture may be worsened by additional concomitant factors [ 29 ]. Indeed, when JBS cases are promptly detected (an increasing number may be perinatally suspected and diagnosed, as in present patients), it is recommended a gentle and less invasive perinatal management, including elective cesarean section and avoidance or minimal use of vascular punctures [ 6 ].…”

“…To date, studies performed in JBS led to the identification of genetic modifiers as likely contributors to the phenotypic variability [ 30 ], in addition to differences in deletion size. Whole genome sequencing will likely provide further insights into the genetic basis of this variability, and have important implications for therapies [ 28 , 31 – 33 ]. Additional risk factors, like those reported in present newborns, must be carefully taken into account and managed by the neonatologist.…”