Bialleleic PKD1 mutations underlie early-onset autosomal dominant polycystic kidney disease in Saudi Arabian families.

BACKGROUND: Polycystic kidney disease (PKD) is one of the most common genetic renal diseases and may be inherited in an autosomal dominant or autosomal recessive pattern. Pathogenic variants in two major genes, PKD1 and PKD2, and two rarer genes, GANAB and DNAJB11, cause autosomal dominant PKD (ADPKD). Early onset and severe PKD can occur with PKD1 and PKD2 pathogenic variants and such phenotypes may be modified by second alleles inherited in trans. Homozygous or compound heterozygous hypomorphic PKD1 variants may also cause a moderate to severe disease PKD phenotype. METHODS: Targeted renal gene panel followed by Sanger sequencing of PKD1 gene were employed to investigate molecular causes in early onset PKD patients. RESULTS: In this study, we report four consanguineous Saudi Arabian families with early onset PKD which were associated with biallelic variants in PKD1 gene. CONCLUSIONS: Our findings confirm that PKD1 alleles may combine to produce severe paediatric onset PKD mimicking the more severe autosomal recessive ciliopathy syndromes associated with PKD. Screening of parents of such children may also reveal subclinical PKD phenotypes.

Severe Vancomycin Intoxication in an Infant Not Needing Dialysis: A Case Report and Literature Review.

Vancomycin nephrotoxicity is a major clinical concern. We report the case of an infant with severe vancomycin intoxication. A literature review was conducted due to the paucity of reported pediatric cases. An infant was treated for suspected meningitis based on cerebrospinal fluid (CSF) cell count and was empirically started on intravenous ceftriaxone and vancomycin while awaiting the results of culture and meningitis/encephalitis polymerase chain reaction (PCR) tests. Day 2 vancomycin trough level was within the target range; however, the repeat day 4 levels were beyond the upper limit of measurement at >400 µg/mL and associated with acute kidney injury (AKI). Vancomycin was immediately discontinued. The child was treated with intravenous hydration and furosemide and did not require dialysis. The short-term kidney function outcome was reassuring. We identified 23 pediatric cases from 1992 to 2021 with high vancomycin serum levels. Vancomycin level ranges between 32-427 µg/mL. Toxic vancomycin serum levels >400 µg/mL were reported in only two patients. Nephrotoxicity developed in 73.9% of cases. Hemodialysis is the most common management intervention while some patients received watchful management. Kidney function impairment is transient in most reported cases, even in those who received no intervention. However, long-term data are lacking. An intervention is not indicated for all cases of vancomycin intoxication, regardless of serum level. However, in cases of severe nephrotoxicity resistant to medical measures or pre-existing kidney dysfunction, kidney replacement therapy (KRT) is needed to manage severe AKI and speed-up vancomycin clearance.

What is Behind Salmonella? Unusual Presentation in Two Pediatric Cases.

Salmonella infection is an international public health concern. Salmonella organisms are Gram-negative bacilli that belong to the family Enterobacteriaceae, and more than 2500 Salmonella serovars have been described. The most common clinical presentations of Salmonella infection are gastroenteritis, bacteremia, enteric fever, and chronic carrier state. Other rare extraintestinal infections include cellulitis, urinary tract infection, pneumonia, endocarditis, meningitis, brain abscess, and osteomyelitis. Salmonella species resistant to first-line treatment such as ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole are referred to as multi-drug resistant. In recent years, extensively drug-resistant (XDR) Salmonella have appeared in Pakistan; XDR strains are resistant to multiple antibiotics, including first-line antibiotics, fluoroquinolones, and third-generation cephalosporins. We report two interesting pediatric cases who presented with uncommon Salmonella infection. The first case is a child diagnosed with XDR typhoid fever in a country where the strain is not endemic. The second case is a child who presented with a Salmonella urinary tract infection who is otherwise immunocompetent and has no apparent underlying structural abnormalities of the urinary tract.

Osteomalacic myopathy due to celiac disease.

Celiac disease is a gluten-sensitive enteropathy characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine. It is well known to be associated with a variety of neurological disorders including epilepsy, myopathy, neuropathy and ataxia. The nature of this association is unclear. Although osteomalacia secondary to vitamin D deficiency is a recognized complication of celiac disease, however, severe osteomalacic myopathy as the only presentation of celiac disease is extremely rare. We present 2 interesting cases of osteomalacic myopathy secondary to celiac disease, which were treated successfully with full recovery. An important and unique observation was the brisk reflexes noticed in both patients. The mechanism behind this phenomenon is not well understood. Work-up for celiac disease is warranted in any young patient that presents with myopathy.