لخّصلي

ARPKD is a rare, monogenic ciliopathy characterized by the formation of bilateral renal cysts and congenital hepatic fibrosis.-The urinary bladder was empty with Foleys catheter in situ, no ascites was seen.last BG: pH: 7.45 PC02: 31.1 HCO3: 22 BE: -11

• Serum Lytes: NA: 133 K: 3.9 Cl: 109
• UA: Leukocytes: 20-23, gravity: 1.015
• BUN: 6 Cr: 0.18
• AST: 96 ALT: 34

• She also had abdominal distention, abdominal U/S was done and showed bilateral medullary nephrocalcinosis and no hepatic hemangiomas.Prenatally, oligohydramnios without any enlargement and/or increased echogenicity of kidneys was observed.

ARPKD is a rare, monogenic ciliopathy characterized by the formation of bilateral renal cysts and congenital hepatic fibrosis. https://www.mdpi.com/1422-0067/22/12/6523. This condition is characterized as a commonly occurring pediatric renal cystic disorder, having an occurrence rate of 1 in every 20,000 individuals. Its etiology is rooted in mutations of the PKHD1 gene which is also known as polycystic kidney and hepatic disease-1 or ciliary IPT domain containing fibrocystin/polyductin and is located on chromosome 6p12. https://ijponline.biomedcentral.com/articles/10.1186/s13052-020-00922-4 The clinical spectrum of the disease displays a high degree of variability, encompassing a range of presentations that can include late-onset milder forms as well as severe perinatal manifestations. https://ijponline.biomedcentral.com/articles/10.1186/s13052-020-00922-4#ref-CR2
While pediatricians commonly encounter dysmorphic features or liver cysts in patients with ARPKD, reported cases of multiple skin hemangiomas in individuals with this condition are uncommon.

Presentation:
A female newborn was delivered at 40 weeks of gestation, by cesarean section for fetal distress. Her parents were second-grade cousins and more originating from Palestine. The father has FMF and history of renal stones and, her four-year old brother has hydronephrosis and her sister diagnosed with PKD4 with or without hepatic disease confirmed by identifying a homozygous pathogenic variant in PKHD, while her other brother is healthy. Pregnancy history was uneventful. Prenatally, oligohydramnios without any enlargement and/or increased echogenicity of kidneys was observed. At birth, anthropometric measurements were as follows: weight 2100 g (98th centile), length 47 cm (84th centile), and occipitofrontal circumference 30 cm (58th centile). Apgar scores were 7 and 8 at 1 and 5 min, respectively. On physical examination she showed the typical Potter sequence face (flattened nose, micrognathia, large low-set ears and triangular face) and long eyelashes, otherwise, she was healthy and didn’t need NICU.
She was in her usual state of health until 4-month age when she developed fever and cough which required two admissions with a month apart as case of chest infection that was treated with IV antibiotic. At age of 5 months, the mother noted that she complained of decreased oral intake, poor weight gain with continuous abdominal distention and occasional constipation, also, she noticed episodic bilateral inguinal bulges, which later diagnosed as bilateral inguinal hernias.
At the age of 6-months, she developed fever (38.5 axillary), vomiting many times, mucous non bloody watery diarrhea, so admitted to hospital for 2 days and stool analysis was done and was positive for ameba histollica (WBC 4_6 cells) she started ampicillin and fluid and discharged on ORS and metronidazole. Because the patient still has vomiting, diarrhea and hypoactivity, she was admitted again, and labs were:
*CRP=2.36, WBC 95.2. stool was +ve for rotavirus.

• BG showed pH: 7.35 PCO2: 26 HCO3: 8.6 BE: -16, she was given Bicarb. last BG: pH: 7.45 PC02: 31.1 HCO3: 22 BE: -11


• Serum Lytes: NA: 133 K: 3.9 Cl: 109


• UA: Leukocytes: 20-23, gravity: 1.015


• BUN: 6 Cr: 0.18


• AST: 96 ALT: 34

• She also had abdominal distention, abdominal U/S was done and showed bilateral medullary nephrocalcinosis and no hepatic hemangiomas. So she was referred to a pediatric nephrologist. Who was done the following:

• Labs:
  Ammonia: 43 Lactic acid: 3.1 Ph: 7.50, Pco2: 26, Hco3: 26 K: 4.3, Na: 140, Cl: 102, Cr: 0.27,
  Ca: 10.3, Mg: 2.01 ,Vit D: 22


• Urine:
  Ca/Cr: 0.26 (normal), U/A: urine ph: Acidic, SG: 1010, Pro: NIl, RBC: 0-2.
  *Abdominal US:
  -Bilateral nephrocalcinosis

• Heterogeneous coarse liver with dilated intra and extra hepatic biliary tree, congenital hepatic fibrosis was suspected.
  *Pediatric nephrologist advised to do WES.

At 7 months of age, the mother noticed that hemangiomas were increasing in size and another 2 hemangiomas developed over her both arms.

At age of 9 months, exome sequencing analysis was performed on and the result was positive. The homozygous mutation NM _ 138694.4: c.4870C > T ( p.Arg1624Trp) of the PKHD1 gene was identified in the proband.
There is known / expected pathogenic variants in genes shared by the parents ( i.e. shared carrier status ) and on the maternal X - chromosome. It causes a missense mutation at the amino acid 1624 of the encoded protein.

At age of 11 months, she was admitted due to abdominal distention and constipation, so abdominal U/S was done and showed:
-The liver showed heterogeneous echotexture, congenital hepatic fibrosis should be considered as the patient has PCKD for clinical correlation

• The gall bladder appeared normal without evidence of wall thickening or stones, the common bile duct is not dilated.


• the spleen appeared normal.
  -Both kidney was enlarging in size and show echogenic medullary pyramids some of them with twinkling artifact suggestive of Medullary nephrocalcinosis as well as mild bilateral pelvicalyceal dilatation, there is also right lower pole renal cyst of about 1.3cm. the right kidney measuring about 8.5cm and the left 9.6 cm with cortical thickness of about 4_5mm for each.
  -The urinary bladder was empty with Foleys catheter in situ, no ascites was seen.