Rare Genetic Syndrome Unmasked by Sudden Kidney Failure in Young Woman

A 27-year-old woman arrived at the emergency department of Jinnah Hospital in Lahore, Pakistan, with a week of worsening vomiting, diarrhea, fever, and a troubling drop in urine output. What looked at first like a severe bout of gastroenteritis turned out to be something far more consequential. Blood tests revealed catastrophic kidney failure, with serum creatinine measured at 8.8 mg/dL against a normal upper limit of 1.2 mg/dL, and serum urea at 324 mg/dL, more than eight times the reference ceiling. Yet the most striking discovery was not the severity of the acute illness but what lay beneath it: imaging showed bilaterally shrunken, scarred kidneys, evidence that chronic kidney disease had been silently destroying her renal tissue for years without anyone ever having diagnosed it.

The acute crisis, physicians concluded, was an episode of acute kidney injury superimposed on advanced, previously unrecognized chronic kidney disease, precipitated by the dehydration of her gastrointestinal illness. She had never undergone renal ultrasound, biochemical kidney function testing, or assessment of her estimated glomerular filtration rate, because she had never before sought medical care for her underlying condition. The case, published as a case report in Clinical Case Reports, documents how a rare multisystem genetic disorder called Bardet–Biedl syndrome went entirely undiagnosed into adulthood, allowing progressive kidney damage to accumulate unchecked until a routine infection brought the hidden disease to the surface.

Bardet–Biedl syndrome is a rare autosomal recessive ciliopathy, meaning it arises from defects in the primary cilium, a tiny antenna-like organelle that projects from nearly every cell in the body and coordinates crucial developmental and signaling pathways. The syndrome is defined by a constellation of features: rod–cone dystrophy of the retina that typically begins as night blindness and progresses to blindness, central obesity, extra fingers or toes known as polydactyly, intellectual disability, hypogonadism or genitourinary anomalies, and kidney involvement. Because the condition shows variable penetrance, its presentation can differ dramatically even among siblings in the same family, complicating recognition. In European outbred populations, prevalence is estimated at roughly one in 125,000 to one in 160,000 people, but isolated communities with founder mutations can carry far heavier burdens, most famously the Faroe Islands, where a single BBS1 splice-site mutation produces a prevalence of one in 3,700.

The patient in Lahore carried nearly the full textbook picture. Blind since age 19 after night blindness first appeared at age 8, she had a body mass index of 29, primary amenorrhea, childhood intellectual disability, bilateral polydactyly of both hands and feet, widely spaced eyes, strabismus, and a history of cystostomy for urethral stricture. Two of her siblings were affected by a similar constellation of problems, and she was born to first-cousin parents, a consanguinity pattern that dramatically raises the probability of homozygosity for recessive disease alleles. Laboratory workup added further findings: severe macrocytic anemia with hemoglobin of 6.8 g/dL, elevated alkaline phosphatase at 480 U/L, and an HbA1c of 8.2 percent with random glucose of 250 mg/dL, indicating poorly controlled diabetes mellitus that had also escaped prior diagnosis.

Imaging sealed the clinical picture. Abdominal ultrasound showed coarse liver echotexture, mild splenomegaly, and kidneys with increased echogenicity and reduced corticomedullary differentiation, hallmarks of chronic parenchymal damage. Computed tomography of the kidneys, ureters, and bladder then demonstrated bilaterally small kidneys, the right measuring 83 by 27 millimeters and the left 83 by 33 millimeters, with lobulated, irregular cortices consistent with longstanding scarring. In a young adult, kidneys of this size and texture represent years of accumulated nephron loss. The combination of retinal dystrophy, kidney disease, polydactyly, obesity, intellectual disability, primary amenorrhea, and affected siblings pointed decisively toward a hereditary ciliopathy, and the principal differential, Alström syndrome, was excluded because it does not typically involve polydactyly or intellectual disability. A clinical diagnosis of Bardet–Biedl syndrome was made, though genetic confirmation was not pursued because of resource limitations.

At the molecular level, BBS is strikingly heterogeneous: at least 26 genes have been identified, most encoding proteins essential for ciliary assembly and intracellular trafficking. Disruption of ciliary signaling, including the non-canonical Wnt pathway, is implicated in the cystogenesis and progressive nephron loss that characterize BBS-related kidney disease. Genotype–phenotype studies suggest that patients with variants in chaperonin-like genes such as BBS6, BBS10, and BBS12 tend to develop more severe chronic kidney disease than those with BBS1 variants, a finding that could eventually guide how intensively clinicians surveil renal function once sequencing becomes accessible in settings like Pakistan. Diagnostic criteria originally proposed by Beales and colleagues require either four primary features or three primary features plus two secondary ones, and a recent European Reference Networks consensus has updated the framework to incorporate molecular diagnosis alongside clinical findings. This patient fulfilled the primary criteria of rod–cone dystrophy, postaxial polydactyly, obesity, intellectual disability, genitourinary anomalies, and renal dysfunction.

What makes the case exceptional is timing. The mean age of clinical BBS diagnosis is around nine years, yet this patient reached her third decade without a formal syndromic diagnosis of any kind. Renal involvement affects more than half of BBS patients and is the leading driver of premature mortality in the syndrome, ranging from structural anomalies such as fetal lobulation and increased parenchymal echogenicity to cystic dysplasia and progressive loss of glomerular filtration. In the largest reported cohort, kidney failure requiring renal replacement therapy occurred in roughly 6 percent of adult and 5 percent of pediatric patients, and affected children tend to follow one of two trajectories, either developing severe chronic kidney disease early or remaining comparatively spared through childhood. An early warning sign, reduced urinary concentrating capacity producing polyuria and polydipsia, reflects tubular dysfunction tied to disrupted ciliary signaling and can flag declining renal function years before crisis.

Treatment of the acute episode followed standard nephrology practice. The patient received three sessions of hemodialysis, broad-spectrum antibiotics, intravenous fluids, and antipyretics, and improved over subsequent days with a notable recovery of urine output before discharge with strict follow-up advice. Her echocardiogram was normal, reassuring given that cardiovascular abnormalities have been documented in a subset of BBS patients. Longer-term management of the syndrome demands a genuinely multidisciplinary approach spanning nephrology, ophthalmology, endocrinology, genetics, and cardiology, with regular blood pressure monitoring, annual ophthalmologic evaluation, and periodic assessment of renal and metabolic parameters. Should her kidneys progress to outright failure, renal transplantation remains viable with outcomes comparable to the general population, although coexisting obesity can complicate both pre-transplant workup and post-transplant metabolic management. No disease-modifying therapy yet exists for the renal or retinal manifestations, making surveillance the principal tool for delaying irreversible complications.

The Pakistani context adds a public-health dimension. Roughly half to two-thirds of marriages in the country are consanguineous, most commonly between first cousins, a pattern that should, in principle, elevate the prevalence of autosomal recessive disorders like BBS. Yet reported Pakistani cases remain scarce, a paradox the report’s authors attribute to underdiagnosis rather than genuinely low prevalence, driven by limited access to ophthalmologic, nephrologic, and genetic testing. A recent case series from Multan described four affected individuals from two sibling pairs, illustrating both marked intrafamilial variability and diagnostic delay, and the literature now includes scattered reports from Dera Ismail Khan, Peshawar, Karachi, and Islamabad. Most patients present in childhood or adolescence with retinal and developmental features and are diagnosed clinically rather than genetically, and the present case appears to be among the few from Pakistan in which unrecognized chronic kidney disease progressed to acute kidney injury in adulthood before the underlying syndrome was ever identified.

The broader lesson reaches beyond one hospital ward. Bardet–Biedl syndrome’s features can appear so scattered across specialties, an eye problem here, extra digits there, obesity and developmental delay elsewhere, that no single clinician assembles the full picture until something acute forces the issue. Greater awareness among pediatricians, ophthalmologists, and family physicians, combined with systematic renal surveillance of children showing the syndrome’s cardinal features, could allow earlier diagnosis and potentially forestall exactly the kind of delayed, dramatic presentation seen in Lahore. Genetic counseling remains central to comprehensive care, informing families about recurrence risk and the value of screening apparently healthy relatives for subclinical complications. For this 27-year-old woman, the gastroenteritis that nearly overwhelmed her kidneys also finally gave her disease a name, and with it, at last, the possibility of coordinated care.

Subject of Research: Bardet–Biedl syndrome presenting as acute kidney injury on undiagnosed chronic kidney disease in a young adult

Article Title: Bardet–Biedl Syndrome Presenting With Acute Kidney Injury Revealing Previously Undiagnosed Advanced Chronic Kidney Disease in a Young Adult: A Case Report

Article References: Abbas, A., Amjad, N., Mufti, A. F., Waqas, M., Iqbal, M., Ali, H., Habib, A., Samadi, Y., & Haider, M. U. (2026). Bardet–Biedl Syndrome Presenting With Acute Kidney Injury Revealing Previously Undiagnosed Advanced Chronic Kidney Disease in a Young Adult: A Case Report. Clinical Case Reports, 14(10), Article e73672. https://doi.org/10.1002/ccr3.73672

Image Credits: AI Generated

DOI: 10.1002/ccr3.73672

Keywords: Bardet-Biedl syndrome, ciliopathy, acute kidney injury, chronic kidney disease, polydactyly, rod-cone dystrophy, consanguinity, Pakistan, hemodialysis, genetic diagnosis, primary cilium, rare disease