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CASE REPORT Table of Contents  
Ahead of print publication
A 27-year-old man with rare genetic disorder presented with morbid obesity


1 Department of Endocrinology, North East Medical College, Sylhet, Bangladesh
2 Department of Medicine, North East Medical College, Sylhet, Bangladesh
3 Department of Endocrinology, Dhaka Medical College, Dhaka, Bangladesh
4 Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
5 Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh

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Date of Submission28-May-2022
Date of Decision06-Jun-2022
Date of Acceptance06-Jun-2022
Date of Web Publication25-Jul-2022
 

  Abstract 


Overweight and obesity are rapidly increasing globally, and Bardet–Biedl syndrome (BBS) is a rare genetic disorder that can cause obesity. We report a case of a 27-year-old unmarried man with morbid obesity, retinal dystrophy, polydactyly, mental retardation, hypogonadism, and poor scholastic performance diagnosed as BBS who was admitted to our care.

Keywords: Bardet–Biedl syndrome, hypogonadism, obesity, polydactyly, retinitis pigmentosa


How to cite this URL:
Hannan MA, Selim M A, Rahman A A, Al Razy A, Saifuddin M, Selim S, Kamrul-Hasan A B. A 27-year-old man with rare genetic disorder presented with morbid obesity. Bangladesh J Endocrinol Metab [Epub ahead of print] [cited 2022 Aug 10]. Available from: http://www.bjem.org/preprintarticle.asp?id=352102





  Introduction Top


Bardet–Biedl syndrome (BBS) is a rare autosomal recessive genetic disorder with varied clinical presentations.[1] In the 1880s, four siblings in a family with retinitis pigmentosa, obesity, and intellectual impairment were described by Laurence and Moon. The affected family members later develop spastic paraparesis. In 1920 and 1922, Bardet and Biedl independently described two similar cases of obesity, retinitis pigmentosa, and additional polydactyly. From 1925, the syndrome was known as Laurence–Moon–BBS. Later, it was considered two entities, Laurence–Moon and BBSs, but mutations in known BBS genes have been seen in families with both syndromes. Hence, it is most usually known as BBS.[2] Now, BBS is considered a separate entity with modified diagnostic criteria consisting of primary and secondary features. Primary features are rod-cone dystrophy, polydactyly, obesity, learning disabilities, renal anomalies, and hypogonadism in males. Secondary features are speech disorder or delay, strabismus or cataracts or astigmatism, brachydactyly or syndactyly, nephrogenic diabetes insipidus, ataxia or poor coordination or imbalance, mild spasticity, diabetes mellitus (DM), dental crowding or hypodontia or small roots or high arched palate, left ventricular hypertrophy or congenital heart disease, and hepatic fibrosis.[1] The presence of four primary features or three primary features plus two secondary features is considered to be diagnostic of BBS.[3] Genetic analysis is needed for definitive diagnosis, which shows mutation of the BBS gene.[1] Herein, we report the case of a 27-year-old man who presented with morbid obesity and obesity consequence. Both common and uncommon causes were searched for the etiology of morbid obesity. Finally, the case was diagnosed as a rare genetic disorder, BBS, as the underlying cause of this obesity.


  Case Report Top


A 27-year-old obese unmarried male was admitted to the Department of Medicine, North East Medical College and Hospital, Sylhet, with complaints of abdominal pain and vomiting for 3 weeks. The pain was in the epigastric region, burning in nature, relieved by medication such as an antacid. Vomiting was spontaneous, mixed with both digested and undigested food materials, and not bile stained. The patient also complained of fever for 3 weeks, which was associated with chill and rigor. He was the only son of his nonconsanguineous parents. His antenatal, natal, and postnatal periods were uneventful. Developmental milestones were normal as per age except for his intelligence, school performance, and gradual weight gain. On examination, the patient was ill-looking and not well oriented. The speech was poor in content and not fluent. His body weight was 105 kg, height was 160 cm, and body mass index (BMI) was 41.02 kg/m2 [Figure 1]. The patient was mildly icteric, mildly dehydrated, but not anemic. His pulse was 100 bpm, blood pressure –90/60 mmHg, and temperature –102oF; he had polydactyly in the left hand [Figure 2]. There was acanthosis nigricans [Figure 3] over the neck and axillae; there was no lymphadenopathy and thyromegaly. According to Tanner's staging, testicular volume was 6 mL (bilaterally), pubic hair stage 3, stretched penile length –7cm, and bilateral gynecomastia. Abdominal examination revealed a distended abdomen, white striae over the lower abdomen, mild tenderness over the epigastric region, and no organomegaly. Examination of the fundus revealed bilateral retinitis pigmentosa. Investigation revealed: mild anemia (hemoglobin: 11.6 gm/dL), normal total and differential counts of white blood cells, erythrocyte sedimentation rate –97 mm in 1st h, normal urine R/E, serum creatinine –2.0 mg/dL, chest X-ray – normal, normal electrocardiography, fasting plasma glucose –9.8 mmol/L and 2 h plasma glucose –10.2 mmol/L at oral glucose tolerance test, HbA1C –5.3%, fasting total cholesterol –90 mg/dL, high-density lipoprotein cholesterol –16 mg/dL, low-density lipoprotein cholesterol –50 mg/dL, triglyceride –118 mg/dL, and serum thyroid-stimulating hormone level was 1.11 μIU/mL. Ultrasonography of the whole abdomen revealed a fatty change in the liver, thick collection in the left perirenal space, and upper gastrointestinal endoscopy revealed a chronic duodenal ulcer [Table 1]. Serum testosterone, luteinizing hormone, follicular stimulating hormone, and cortisol were not assessed due to the financial constraints of the patient. Based on the above findings, he was diagnosed as a case of BBS with morbid obesity, DM, fatty liver, dyslipidemia, chronic duodenal ulcer, and perinephric abscess with acute kidney injury.
Figure 1: Morbid obesity

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Figure 2: Polydactyly

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Figure 3: Acanthosis nigricans

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Table 1: Laboratory findings of the patient

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  Discussion Top


BBS is a rare genetic disorder. The current prevalence in North American and European populations ranges from 1/140,000 to 160,000 live births. Populations with a high rate of consanguinity or from isolated regions have been characterized by a higher frequency of BBS such as for Kuwait (1:17,000) and Newfoundland (1:18,000).[4] In the last two decades, 21 BBS genes have been identified, mutations in which account for 80% of cases with a clinical diagnosis of BBS.[2] It has a multisystem involvement with variable clinical manifestations. Rod-cone dystrophy (90%–100%), obesity (72%–92%), polydactyly (63%–81%), genital anomalies (59%–98%), learning difficulties (50%–61%), and renal anomalies (20%–53%) are the major components of BBS.[5] Speech disorders (54%–81%), developmental delay (50%–91%), DM (6%–48%), dental anomalies (51%), congenital heart disease (7%), brachydactyly/syndactyly (46%–100%), ataxia/poor coordination (40%–86%), cardiopathy (10%), deafness (11%–12%), and anosmia/hyposmia (60%) are the minor components of BBS.[5] According to this, at least four major criteria or three major and two minor criteria together are sufficient for a diagnosis.[5] Our case fulfilled five primary features for the diagnosis of BBS. Retinal dystrophy is the most common major manifestation present in BBS. The patient usually presents with night blindness which gradually progresses to blindness. The mean age at which patient complains of night blindness is 8.5 years (range: 1–34 years), and by 15.5 years (range: 8–43 years), most of them are registered blind.[1] The onset in BBS patients is, therefore, earlier than in isolated typical retinitis pigmentosa, and progression is rapid, with a mean of 7 years from diagnosis to blindness.[6] In our case, minimal night blindness complained of bilaterally retinitis pigmentosa. Obesity (current incidence: 72%–92%) is the second major feature in BBS patients; beginning in early childhood and becoming severe with age, it appears to be widespread and diffuse.[4] Some BBS patients develop type 2 diabetes which can be related to the degree of obesity.[4] Our case is morbidly obese (BMI- 41.02 kg/m2) with obesity complications such as DM, fatty liver, GERD, acanthosis nigricans, obstructive sleep apnea, depression, and cognitive impairments. Our case is interesting as the patient presented with morbid obesity and its complication, but the underlying cause of this morbid obesity is a rare genetic syndrome such as BBS beyond the common cause. This case report emphasizes that a young patient with morbid obesity can be due to a rare genetic disorder. Hence, one should also consider the rare possible etiologies besides the common ones. Hypogonadism manifest as delayed puberty or hypogonadism in males and genital abnormalities (59%–98%) in females.[4] Our case has hypogonadism (testicular volume bilaterally: 6mL, pubic hair stage 3, SPL-7cm, and bilateral gynecomastia). Neuropsychiatric manifestations have been described in BBS patients, including intellectual disability, learning difficulties (50%–61%), speech deficits, and behavioral problems such as autistic traits and psychosis. The primary cilium is one of the important organelles in human brain cells and is necessary for neurogenesis signaling and hippocampal development.[4] Our patient also has learning difficulties (he could not continue his education due to his low intelligence quotient). Polydactyly-type limb anomalies are the third major feature in BBS and may be the only clinical sign present at birth. Classically, polydactyly is postaxial (63%–81%) in BBS patients. Other limb defects such as brachydactyly or syndactyly (46%–100%) are frequently reported for both hands and feet.[4] Our patient had polydactyly in his left hand. Renal failure is a major cause of morbidity and mortality in BBS patients. The renal abnormalities (20%–53%) are variable but classically manifest with cystic tubular disease and anatomical malformations. Most BBS patients have been characterized as having urinary concentration defects with normal renal function and no major cysts.[4] Renal anomalies are seen in 20%–53% of children with BBS, the most common presentation being structural anomalies (renal parenchymal cysts, calyceal cysts, vesicoureteric reflux, and horseshoe kidney).[1] Some may manifest as chronic kidney disease and abnormal urine analysis.[1] An ultrasound scan of the abdomen of our patient showed no significant renal anomalies except left perirenal collection. A definite diagnosis of BBS requires genetic analysis, which shows mutation of the BBS gene.[1] Due to financial constraints, we could not arrange genetic analysis.


  Conclusion Top


A rare cause of obesity such as BBS should be sought besides the common one when a patient presents with other associated findings such as poor school performances, mental retardation, polydactyly, and hypogonadism. Good history, detailed clinical examination, and ocular examination help diagnose BBS in resource-poor countries even if the genetic analysis is not available.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Shrestha S, Chaudhary N. A rare case of obesity. Can it be Bardet-Biedl syndrome? Clin Case Rep 2019;7:1725-8.  Back to cited text no. 1
    
2.
Forsythe E, Kenny J, Bacchelli C, Beales PL. Managing Bardet-Biedl syndrome – Now and in the future. Front Pediatr 2018;6:23.  Back to cited text no. 2
    
3.
Dosi RV, Bhatt NR, Ambaliya AP, Sonune NN, Patell RD. Bardet Biedel syndrome: A very rare entity in India. J Clin Diagn Res 2013;7:2010-1.  Back to cited text no. 3
    
4.
M'hamdi O, Ouertani I, Chaabouni-Bouhamed H. Update on the genetics of Bardet-Biedl syndrome. Mol Syndromol 2014;5:51-6.  Back to cited text no. 4
    
5.
Sahin C, Huddam B, Akbaba G, Tunca H, Koca E, Levent M. Two brothers with Bardet-Biedl syndrome presenting with chronic renal failure. Case Rep Nephrol 2015;2015:764973.  Back to cited text no. 5
    
6.
Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA. New criteria for improved diagnosis of Bardet-Biedl syndrome: Results of a population survey. J Med Genet 1999;36:437-46.  Back to cited text no. 6
    

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Correspondence Address:
Mohammad Abdul Hannan,
Department of Endocrinology, North East Medical College, Sylhet
Bangladesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjem.bjem_6_22



    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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    -  Hannan MA
    -  Selim M A
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    -  Saifuddin M
    -  Selim S
    -  Kamrul-Hasan A B


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