Alström–Hallgren Syndrome: Rare Ciliopathy Insights

Alström–Hallgren syndrome represents one of the most clinically intricate and genetically fascinating monogenic disorders known to medical genetics. Characterized by progressive multiorgan dysfunction arising from ciliary structural deficits, it stands as an archetypal model for studying systemic metabolic control, sensory neurodegeneration, and progressive multi-organ fibrosis. Understanding this exceptionally rare condition illuminates vital pathways connecting basic cellular architecture to profound human physiological pathologies.

Alström–Hallgren Syndrome

1. Concise Definition

Alström–Hallgren syndrome (most frequently designated in modern clinical literature as Alström syndrome) is an ultra-rare, progressive, autosomal recessive monogenic disorder categorized as a primary ciliopathy, caused by loss-of-function mutations in the ALMS1 gene located on chromosome 2p13.1. It is clinically delineated by an exhaustive constellation of phenotypic manifestations, including early-onset cone-rod retinal dystrophy, progressive neurosensory sensorineural hearing impairment, severe childhood truncal obesity, extreme insulin resistance with hyperinsulinemia, pediatric type 2 diabetes mellitus, dilated or restrictive cardiomyopathy, and systemic multiorgan fibrosis affecting the liver, kidneys, and pulmonary systems.

Unlike historically linked conditions such as Bardet–Biedl syndrome, Alström–Hallgren syndrome is distinctly recognized by the preservation of normative cognitive capacity in the vast majority of patients and the total absence of limb dysmorphism, such as postaxial polydactyly. Over time, the condition precipitates progressive end-organ failure, rendering it a life-limiting systemic illness that necessitates coordinated, lifelong multidisciplinary surveillance.

2. Etymology and Linguistic Origin

The syndrome derives its eponym from the prominent Swedish neuropsychiatrist Carl-Henry Alström and his collaborators, particularly child psychiatrist Bertil Hallgren, alongside Lars-Börje Nilsson and Henrik Asander. In 1959, this clinical group published their seminal monograph detailing a hereditary syndrome characterized by retinal degeneration accompanied by obesity, diabetes mellitus, and severe neurogenous deafness across a consanguineous kindred in Sweden.

Linguistically, the term compounds the Scandinavian surnames “Alström” (historically rooted in the Swedish elements al, meaning alder tree, and ström, meaning stream or river) and “Hallgren” (derived from hall, meaning rock or boulder, and gren, meaning branch). While historically cataloged as Alström–Hallgren syndrome in continental Europe to credit Hallgren’s diagnostic and psychiatric evaluations of the kindred, modern medical nomenclatures such as the Mendelian Inheritance in Man (OMIM #203800) universally index the construct under the primary designation of Alström syndrome, retaining the compound eponym within historical nosological compendiums.

3. Pronunciation and Grammatical Form

Pronunciation: Phonetically transcribed in International Phonetic Alphabet (IPA) as /ˈɑːl.strøm ˈhɑːl.ɡreɪn ˈsɪn.droʊm/ (UK/US adapted: /ˈɑːl-strəm ˈhɑːl-ɡrɛn ˈsɪn-droʊm/).

Grammatical Form: Compound proper noun phrase. The term is predominantly employed as an uncounted clinical diagnostic entity. In syntactic constructions, it regularly serves as an attributive noun modifier (e.g., “Alström–Hallgren syndrome phenotypes,” “an Alström–Hallgren kindred”). Variations in the medical literature include “Alström syndrome,” “Alstrom disease,” and historical designations such as “hereditary retino-oto-diabetic syndrome.”

4. Detailed Conceptual Explanation

At its mechanistic core, Alström–Hallgren syndrome is a systemic disorder of the centrosome and the basal body of primary cilia. Primary cilia are solitary, immotile organelles projecting from the surface of nearly all vertebrate cells, functioning as specialized antennae that transduce extracellular chemical, mechanical, and morphogenetic signals. Pathogenic variants in the ALMS1 gene perturb ciliary function, thereby destabilizing a wide spectrum of fundamental signaling cascades across various anatomical tissues.

The phenotypic chronology typically begins in infancy or early childhood. The earliest observable feature is often ocular: infants exhibit profound photophobia and prominent nystagmus, signaling the onset of progressive cone-rod dystrophy. Unlike classic retinitis pigmentosa, which manifests as an initial breakdown of peripheral rod photoreceptors causing night blindness, Alström–Hallgren syndrome primarily impairs central, cone-mediated visual acuity during early infancy. Histologically, cone photoreceptor outer segments fail to maintain structural integrity, leading to severe visual loss and clinical legal blindness, typically before the second decade of life.

Concurrently, metabolic derangements develop with startling rapidity. Truncal obesity typically emerges within the first year of life, fueled in part by hypothalamic signaling dysfunction that disrupts normal satiety mechanisms. As childhood progresses, patients experience severe resistance to both endogenous and exogenous insulin. This state manifests clinically as marked acanthosis nigricans, premature adult-onset-style dyslipidemia (characterized by hypertriglyceridemia severe enough to induce acute pancreatitis), and metabolic dysfunction-associated steatotic liver disease (MASLD). Without aggressive management, these metabolic disruptions progress to overt type 2 diabetes mellitus, which frequently presents during puberty or early adolescence.

Cardiovascular disease in Alström–Hallgren syndrome presents a distinctive, biphasic clinical trajectory. Approximately 40% of patients develop severe, infantile-onset dilated cardiomyopathy within the first weeks or months of life, which can trigger sudden congestive heart failure. Curiously, in patients who survive this initial phase through vigorous medical management, systolic cardiac function often temporarily recovers, occasionally normalizing for years. However, in adolescence or early adulthood, progressive cardiac disease frequently re-emerges, transforming into an aggressive, infiltrative restrictive or dilated cardiomyopathy driven by extensive interstitial myocardial fibrosis.

The defining pathophysiological hallmark distinguishing Alström–Hallgren syndrome from almost all other hereditary metabolic syndromes is its unchecked, progressive systemic fibrosis. Patients exhibit widespread connective tissue expansion that directly infiltrates the myocardium, hepatic parenchyma, renal glomeruli and tubules, and pulmonary alveolar architecture. Fibrotic disruption ultimately causes chronic kidney disease (CKD) characterized by progressive glomerulosclerosis, portal hypertension secondary to hepatic cirrhosis, and restrictive lung disease, which together contribute heavily to adult mortality.

5. Historical Development

The nosological history of Alström–Hallgren syndrome represents an important chapter in the clinical separation of complex pleiotropic disorders. Prior to 1959, patients exhibiting concomitant obesity, sensory degradation, and endocrine abnormalities were uniformly diagnosed with Laurence–Moon–Biedl syndrome (later segregated into Bardet–Biedl syndrome and Laurence–Moon syndrome). This conflation obscured unique clinical distinctions and impaired genetic understanding.

In 1959, Carl-Henry Alström, working in tandem with Bertil Hallgren, Lars-Börje Nilsson, and Henrik Asander at the Psychiatric Clinic of Karolinska Institutet in Stockholm, conducted an exhaustive clinical, genealogical, and endocrinological analysis of an isolated rural Swedish population. They identified three related patients presenting with an atypical syndrome distinct from Laurence–Moon–Biedl. Their seminal 1959 monograph confirmed that these individuals lacked polydactyly and displayed normal cognitive faculties, while possessing juvenile neurogenous deafness, progressive retinal degeneration, marked early adiposity, and hypergonadotropic hypogonadism, thus defining a completely distinct clinical entity.

Over the following four decades, clinical descriptions accumulated globally, reinforcing that this condition formed an authentic, discrete clinical entity with an autosomal recessive inheritance pattern. A milestone occurred in 2002, when two independent research teams—Collin et al. at The Jackson Laboratory and Hearn et al. in the United Kingdom—simultaneously cloned and identified the causative locus on chromosome 2p13.1, designating the transcript as ALMS1. This molecular discovery firmly repositioned the disease within the emerging medical framework of primary ciliopathies, initiating modern functional investigations into basal body biology.

6. Theoretical Foundations

Alström–Hallgren syndrome is conceptually framed within modern ciliary biology and molecular pathology. The central theoretical model posits that structural disruption of the centrosomal/basal body complex destabilizes transmembrane receptor localization, vesicular trafficking, and downstream signaling cascades that depend on primary cilia.

The primary ciliary axoneme arises directly from the mother centriole, which transitions into the basal body anchored to the apical cell membrane. The ALMS1 gene encodes a massive, widely expressed protein of 4,169 amino acids, localized specifically to the centrosomes and basal bodies of ciliated cells. Current cell biology frameworks hypothesize that the ALMS1 protein operates as a structural scaffold within the proximal ends of centrioles, coordinating the docking of cytoplasmic vesicles and facilitating endosomal recycling.

A second foundational theory links ALMS1 deficiency to unrestrained transforming growth factor-beta (TGF-β) and platelet-derived growth factor (PDGF) signaling pathways. In the absence of functional ALMS1 protein within primary cilia, cellular mechanisms governing cell cycle exit, myofibroblast differentiation, and extracellular matrix deposition become profoundly dysregulated. Rather than terminating tissue repair following physiological cellular stress, ALMS1-deficient fibroblasts undergo unregulated activation, driving pathological extracellular matrix and collagen deposition across diverse visceral organs.

A third theoretical pillar resides in neuroendocrine satiety signaling. Normal leptin and melanocortin signaling within the arcuate nucleus of the hypothalamus depends on primary cilia decorating the surfaces of pro-opiomelanocortin (POMC) and neuropeptide Y (NPY) neurons. When basal body architecture is compromised by ALMS1 mutations, the trafficking of critical neurohormonal receptors—such as the melanocortin 4 receptor (MC4R) and leptin receptor (LEPR)—to the ciliary axoneme is impaired. This molecular disconnect induces relentless central resistance to satiety cues, providing a mechanistic explanation for the extreme hyperphagia, early-onset truncal adiposity, and downstream hyperinsulinemia seen in affected individuals.

7. Key Components, Types, and Dimensions

The multisystem presentation of Alström–Hallgren syndrome can be structured across major physiological organ domains:

• Ophthalmic Dysfunction: Begins as severe infantile photophobia and pendular nystagmus between birth and 15 months of age, progressing from early cone dystrophy to mixed cone-rod retinal dystrophy, culminating in total blindness typically before 20 years of age.
• Auditory Manifestations: Characterized by progressive, symmetrical sensorineural hearing loss starting in the high frequencies during the first decade of life, usually necessitating bilateral hearing amplification or cochlear implantation.
• Metabolic and Endocrine Disturbances: Characterized by progressive truncal obesity, hyperleptinemia, severe peripheral insulin resistance with extensive acanthosis nigricans, mixed hyperlipidemia, adolescent-onset type 2 diabetes mellitus, and variable hypogonadotropic or hypergonadotropic hypogonadism.
• Cardiovascular Pathology: Marked by a distinct biphasic course, often featuring acute infantile dilated cardiomyopathy with heart failure, followed by variable mid-childhood stabilization, and subsequent progression to restrictive or dilated cardiomyopathy in adulthood driven by progressive interstitial cardiac fibrosis.
• Hepatorenal and Pulmonary Fibrosis: Progressive multiorgan extracellular matrix accumulation presenting as metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis with splenomegaly and portal hypertension, progressive chronic kidney disease driven by tubulointerstitial nephritis, and restrictive pulmonary lung disease.
• Cognitive and Neurological Profile: Normative intelligence and preserved cognitive faculties in the vast majority of cases, serving as a critical negative discriminator against Bardet–Biedl and Laurence–Moon syndromes, though severe combined sensory deficits (dual sensory loss) can impede standard academic progression.

8. Examples and Illustrative Cases

To contextualize this complex clinical trajectory, consider the classic diagnostic course of an infant presenting at four months of age. The infant is brought to pediatric attention because of persistent, involuntary eye movements (pendular nystagmus) and extreme distress in illuminated environments (marked photophobia). Concurrently, the child displays tachypnea, poor feeding, and lethargy. An initial echocardiogram demonstrates severe dilated cardiomyopathy with a left ventricular ejection fraction under 25%. A temporary diagnosis of viral myocarditis or idiopathic cardiomyopathy is often presumed, while the ocular manifestations are misattributed to isolated congenital nystagmus or ocular albinism. With standard inotropic support, afterload reduction, and diuretics, cardiac parameters stabilize, but the child rapidly develops profound truncal obesity by 12 months of age despite regulated caloric intake.

A second illustrative scenario emerges during the mid-childhood stage of a previously diagnosed child at age eight. The patient now exhibits severe progressive bilateral sensorineural hearing loss requiring hearing aids, while their visual fields are constricted to a small central island due to advanced cone-rod degeneration. Routine laboratory surveillance reveals fasting insulin levels five times the upper reference limit, dark velvety hyperpigmentation around the neck and axillae consistent with acanthosis nigricans, and serum triglycerides exceeding 800 mg/dL. By age 13, the patient develops frank glycosuria and ketosis-resistant type 2 diabetes mellitus. Genetic testing via a targeted next-generation sequencing panel resolves the presentation by identifying compound heterozygous nonsense mutations in ALMS1.

9. Measurement and Assessment

Diagnosing and tracking Alström–Hallgren syndrome requires integrating molecular genetics, electrophysiology, specialized imaging, and longitudinal laboratory monitoring.

Definitive confirmation relies on molecular genetic testing. The ALMS1 gene is exceptionally large, spanning 23 exons and coding for 4,169 amino acids. Direct targeted sequencing, next-generation sequencing (NGS) multigene ciliopathy panels, or whole-exome sequencing (WES) are necessary to identify biallelic pathogenic truncating mutations, including nonsense, frameshift, or critical splice-site variations primarily localized to exons 8, 10, and 16.

Clinical functional assessment relies on specific diagnostic modalities:

• Electroretinography (ERG): Full-field ERG is essential during early infancy. It initially documents severe photopic (cone-driven) pathway dysfunction, followed by progressive scotopic (rod-driven) amplitude reduction, confirming diffuse retinal dystrophy long before characteristic pigmentary retinopathic changes emerge on fundoscopy.
• Audiometric Testing: Serial pure-tone audiometry and brainstem auditory evoked potentials (BAEP) track bilateral progressive high-frequency sensorineural hearing loss.
• Cardiovascular Imaging: Regular transthoracic echocardiography and cardiac magnetic resonance imaging (MRI) with late gadolinium enhancement (LGE) detect early ventricular dilation, subclinical systolic/diastolic dysfunction, and the expansion of interstitial myocardial fibrosis.
• Metabolic Screening: Serial assessments include oral glucose tolerance testing, glycated hemoglobin (HbA1c), fasting lipid profiles, liver function panels, and non-invasive elastography to monitor liver stiffness and steatohepatitis.
• Renal Diagnostics: Surveillance involves tracking estimated glomerular filtration rate (eGFR), serum creatinine, cystatin C, urinary albumin-to-creatinine ratio, and periodic renal ultrasonography to assess parenchymal echogenicity and cortical thinning.

10. Applications and Practical Significance

The practical management of Alström–Hallgren syndrome demands a collaborative, preemptive care framework coordinated across pediatric and adult medical specialties. Because no curative gene therapy currently exists, clinical efforts focus on slowing end-organ degradation, mitigating metabolic complications, and preserving sensory functional independence.

Metabolic interventions must be initiated early. Standard therapeutic protocols employ insulin-sensitizing agents, particularly metformin, complemented by glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve glycemic control, promote weight management, and provide cardioprotective and renoprotective benefits. Severe hypertriglyceridemia requires aggressive intervention using high-potency statins, fibrates, and specialized dietary formulations to lower the incidence of life-threatening acute pancreatitis.

Sensory habilitation represents another critical clinical priority. Because patients face the prospect of dual sensory loss (combined blindness and deafness), timely intervention is essential. This includes early orientation and mobility training, adaptive braille education, low-vision technologies, high-fidelity digital hearing aids, and proactive evaluation for cochlear implantation before profound auditory deprivation compromises oral communication. Multidisciplinary medical homes tailored for rare diseases coordinate regular surveillance between cardiology, endocrinology, nephrology, hepatology, ophthalmology, and audiology to intercept acute decompensations early.

11. Research and Empirical Evidence

Modern empirical investigations into Alström–Hallgren syndrome emphasize the cellular role of ALMS1 and explore avenues for therapeutic intervention. Pioneering work led by researchers such as Jan D. Marshall, Gayle B. Collin, and colleagues at The Jackson Laboratory established international patient registries, defined clinical diagnostic criteria, and characterized the mutational spectrum of ALMS1, identifying over 200 distinct disease-causing variants globally.

Structural and cell biology studies confirm that the ALMS1 protein localizes to the proximal ends of both mother and daughter centrioles. Empirical work using ALMS1 knockout murine models has demonstrated that while primary cilia can still physically assemble in many ALMS1-deficient tissues, their molecular composition and signaling fidelity are severely compromised. Knockout models replicate human phenotypic hallmarks, including progressive neurosensory loss, severe obesity, and pronounced tissue fibrosis.

More recent research has focused on the mechanisms governing unrestrained fibrosis in this condition. Investigations demonstrate that ALMS1-deficient fibroblasts maintain an aberrant, persistently activated phenotype characterized by excessive phosphorylation of SMAD2/3 and hyperactivation of the TGF-β receptor cascade. Preclinical trials evaluating anti-fibrotic agents, including pirfenidone, receptor tyrosine kinase inhibitors, and modulators of the TGF-β pathway, suggest potential utility in attenuating hepatic, renal, and myocardial fibrosis, opening promising avenues for future clinical trials.

12. Cultural and Cross-Cultural Considerations

As an ultra-rare autosomal recessive condition, the epidemiological distribution of Alström–Hallgren syndrome is shaped by geographic and demographic factors. While global prevalence is estimated at approximately one to nine cases per 1,000,000 individuals, higher carrier frequencies and disease clusters occur in geographically or culturally isolated communities with high rates of consanguineous marriages, such as specific populations in the Middle East, North Africa, and historical founder populations like the kindreds described by Alström in Sweden.

Cultural attitudes toward disability, genetic consanguinity, and pediatric metabolic disease significantly influence the speed of diagnosis and the level of familial stigma. In resource-constrained global health systems lacking access to next-generation sequencing and pediatric electroretinography, patients are frequently misdiagnosed with common nutritional obesity, isolated retinitis pigmentosa, or idiopathic cardiomyopathy. This delays supportive care until irreversible multi-organ damage has occurred. Global patient advocacy organizations, notably Alström Syndrome International (ASI), play an important role across cultural contexts by fostering international clinical registries, translating educational materials, and building supportive bridges across linguistic and geographical barriers.

13. Criticisms, Debates, and Limitations

Significant debates persist within clinical genetics regarding the nosological classification and diagnostic boundaries of Alström–Hallgren syndrome. A historically contentious topic was whether this disorder represented an authentic clinical entity distinct from the phenotypic spectrum of Bardet–Biedl syndrome (BBS). Even after the 1959 delineation by Alström and Hallgren, skeptical clinicians maintained that Alström syndrome was simply an unusual variant of BBS lacking polydactyly. This debate was finally resolved by molecular genetics, which demonstrated that BBS is caused by mutations across more than twenty distinct genes encoding the “BBSome” coat complex, whereas Alström–Hallgren syndrome arises from mutations in the distinct structural gene ALMS1.

A second clinical debate concerns whether intellectual disability belongs to the core phenotypic spectrum. While foundational medical doctrine maintains that cognitive capacity is fully preserved in Alström–Hallgren syndrome—serving as a diagnostic contrast with BBS—modern neurodevelopmental evaluations report an elevated prevalence of specific learning differences, receptive language challenges, and neurobehavioral issues (including features of autism spectrum disorder) in a subset of patients. Clinicians continue to debate whether these findings reflect primary central nervous system pathology from ALMS1 deficiency or represent secondary neurodevelopmental consequences of severe, early-onset combined visual and auditory deprivation.

Finally, the mechanisms linking basal body dysfunction to widespread interstitial fibrosis remain an area of ongoing debate. While many investigators argue that loss of ALMS1 directly activates profibrotic signaling cascades, others propose that systemic fibrosis is a secondary consequence of chronic, severe metabolic inflammation, advanced lipotoxicity, and prolonged hyperinsulinemia. Clarifying this relationship is critical for prioritizing targeted drug development.

14. Related Terms and Distinctions

Accurate clinical diagnosis requires distinguishing Alström–Hallgren syndrome from other complex conditions that share overlapping features:

• Bardet–Biedl Syndrome (BBS): Shares obesity, retinal degeneration, and renal disease, but differs markedly by the presence of postaxial polydactyly, typical mild-to-moderate intellectual disability, hypogonadism with distinct structural genital anomalies, and the absence of early-onset infantile cardiomyopathy.
• Laurence–Moon Syndrome: Shares retinal dystrophy and endocrine changes, but is characterized by prominent progressive spastic paraplegia and cognitive impairment, while lacking the severe, early multiorgan fibrosis and infantile cardiomyopathy seen in Alström–Hallgren syndrome.
• Usher Syndrome: Characterized by the combination of sensorineural hearing loss and retinitis pigmentosa, but lacks obesity, insulin resistance, type 2 diabetes mellitus, cardiomyopathy, or systemic fibrotic manifestations.
• Wolfram Syndrome (DIDMOAD): Shares diabetes mellitus, progressive optic atrophy, and sensorineural hearing loss, but is characterized by early central diabetes insipidus and progressive neurodegeneration rather than obesity, cone-rod dystrophy, or severe systemic fibrosis.
• Biemond Syndrome II: A historical dysmorphic syndrome characterized by coloboma, obesity, polydactyly, and hypogonadism, clearly distinguishable by its distinctive ocular morphology, digital abnormalities, and lack of extensive multi-organ involvement.

15. Summary and Key Takeaways

Alström–Hallgren syndrome is an ultra-rare, progressive autosomal recessive primary ciliopathy caused by biallelic loss-of-function variants in the ALMS1 gene on chromosome 2p13.1. Pathologically, it is defined by centrosomal and basal body dysfunction that impairs primary cilia signaling and leads to widespread multiorgan fibrosis.

Key clinical features follow a characteristic chronology: infancy presents with cone-rod retinal dystrophy (manifesting as photophobia and nystagmus), early truncal obesity, and potentially life-threatening infantile dilated cardiomyopathy. Childhood and adolescence see the emergence of progressive sensorineural hearing impairment, severe insulin resistance progressing to type 2 diabetes mellitus, dyslipidemia, hepatic steatosis, and systemic fibrotic remodeling affecting the heart, liver, kidneys, and lungs. Importantly, cognitive abilities are typically preserved, and polydactyly is absent, distinguishing it from Bardet–Biedl syndrome.

Diagnosis is confirmed through molecular genetic sequencing of ALMS1, supported by full-field electroretinography, audiometry, and comprehensive metabolic and cardiovascular screening. Because no definitive curative therapy currently exists, clinical management relies on anticipatory multidisciplinary care focused on sensory rehabilitation, strict metabolic control, cardioprotective regimens, and management of progressive end-organ fibrosis.

References

• Alström, C. H., Hallgren, B., Nilsson, L. B., & Asander, H. (1959). Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness: A specific syndrome (not hitherto described) distinct from the Laurence-Moon-Bardet-Biedl syndrome: A clinical, endocrinological and genetic study. Acta Psychiatrica et Neurologica Scandinavica. Supplementum, 129, 1–35.
• Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., & Naggert, J. K. (2002). Mutations among humans and mice in ALMS1, a novel gene for a dynamic protein present in basal bodies of cilia. Nature Genetics, 31(1), 74–78. https://doi.org/10.1038/ng871
• Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Buffa, V., Baumber, S., Chesshire, H., Danpure, C. J., Dowdle, S. A., Connolly, P. A., Phillips, R. H., Yenumula, V., & Wilson, D. I. (2002). Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome. Nature Genetics, 31(1), 79–83. https://doi.org/10.1038/ng874
• Marshall, J. D., Maffei, P., Collin, G. B., & Naggert, J. K. (2011). Alström syndrome: Genetics and clinical overview. Current Genomics, 12(3), 225–235. https://doi.org/10.2174/138920211795677912
• Tahani, N., Maffei, P., Dollfus, H., Paisey, R., Valverde, D., Milan, G., Han, J. C., Favaretto, F., Phadke, S. R., & Marshall, J. D. (2020). Consensual European recommendations on the diagnosis and management of Alström syndrome. Orphanet Journal of Rare Diseases, 15(1), Article 252. https://doi.org/10.1186/s13023-020-01534-1