|Year : 2013 | Volume
| Issue : 1 | Page : 43-45
The curious case of ageing
Dilip Gude, Aslam Abbas, MAW Zubair
Department of Internal Medicine/Critical Care, Princess Durru Shehvar Children's and General Hospital, Purani Haveli, Hyderabad, Andhra Pradesh, India
|Date of Web Publication||17-Apr-2013|
Department of Internal Medicine/Critical Care, Princess Durru-Shehvar Children's and General Hospital, Purani Haveli, Hyderabad, Andhra Pradesh
Source of Support: Medwin Hospital, Nampally, Hyderabad, Andhra
Pradesh, India,, Conflict of Interest: None
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare hereditary disease characterized by multisystem involvement. Although the patients may sport normal intelligence, the disease takes a considerable toll both physically and psychologically resulting in a debilitating state. It may also be compounded by catastrophic/fatal events of accelerated atherosclerosis such as stroke and myocardial infarction. We discuss our experience with HGPS and review the literature.
Keywords: Atherosclerosis, hutchinson gilford syndrome, progeria
|How to cite this article:|
Gude D, Abbas A, Zubair M. The curious case of ageing. Int J Health Allied Sci 2013;2:43-5
| Introduction|| |
Hutchinson Gilford progeria syndrome (HGPS) is a rare disease with an occurrence of about 1 in 4 million  and throughout the literature only about 100 cases have been reported.  The role of a kid affected by progeria, aptly portrayed by Amitabh Bachchan, in the recent movie 'Paa', brought to notice the knowledge about such a syndrome in the general public. Characterized by rapid ageing, HGPS is an entity of significant cardiovascular and cerebrovascular morbidity secondary to heightened atherosclerosis. We report one such case and discuss the literature.
| Case Report|| |
A 22-year-old male patient presented with progressive shortness of breath for 1 month and increasing drowsiness and bed-ridden state from 10 days. Prior to the onset of symptoms, he was fully functional working at a software teaching center. On examination, he appeared grossly old for his age [Figure 1] along with short stature, significant alopecia and shiny, indurated skin over extremities. His voice had a high pitch and oral exam showed poor hygiene and crowding of teeth. Testicular volume was diminished bilaterally at 10 ml. His blood pressure was 170/96 mm of Hg, heart rate was 112/min, respiratory rate was 24/min and temperature was 100.2F. His jugular venous pressure was elevated at 12 cm. On auscultation, Velcro-crepitations were heard bilaterally. Cardiovascular examination was notable for loud second heart sound. Arterial blood gas analysis showed type II respiratory failure with pCO 2 of 82 mm. Owing to the attendants' collective decision against intubating the patient, he was started on continuous positive airway pressure. Chest X-ray showed bilateral rib crowding and scoliosis, fish-mouth vertebrae, bilateral ground glass appearance of lungs, cardiomegaly and generalized osteopenia [Figure 2]. 2D echo showed dilated right atrium and ventricle with pulmonary arterial hypertension (PAH) of 52 mm of Hg and left ventricular hypertrophy with ejection fraction of 42%. Hb was 12.8 g/dl, Total WBC count was 14,800 with neutrophilia (89%). Lipid profile showed Low density Lipoprotein (LDL)-133 mg/dl, total cholesterol 180 mg/dl, triglycerides 148 mg/dl and HDL-29 mg/dl. Prothrombin time was prolonged at 19 s and platelet count was 450,000. A diagnosis of HGPS was made. Along with Continuous Positive Airway Pressure (CPAP), steroids, aspirin and amoxicillin/clavulanic acid and levofloxacin were added. Telmisartan for blood pressure, wardenafil for PAH and other supportive measures were continued. However, patient deteriorated with worsening hypoxia and succumbed to death.
|Figure 1: Clinical photograph of a patient of Hutchinson-Gilford progeria More Details syndrome showing gross alopecia, atrophic skin, crowded dentition and short stature|
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|Figure 2: Chest X-ray (AP view) of the patient showing crowding of ribs, scoliosis, cardiomegaly (thick arrow), acral osteolysis of distal clavicles (thin arrows) and ground-glass opacities of lung fields|
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| Discussion|| |
HGPS results from mutations in the gene LMNA, which encodes the nuclear matrix protein lamin A. There is activation of a cryptic splice donor site in exon 11, producing an abnormal lamin A protein termed progerin,  the accumulation of which perturbs the integrity of the nuclear scaffold leading to nuclear blebbing. Lamin A production also results in decreased telomere length via a direct effect. Apart from telomere attrition, HGPS has accelerated pathological changes that govern ageing, including genomic instability, premature senescence and defective stem cell homeostasis.  Lipofuscin, an important marker of aging, is extensively deposited in various organs like kidneys, brain, adrenal glands, liver, testes, and heart.  Another similar factor that mirrors the underlying ageing process is the increased excretion of hyaluronic acid.  HGPS sports a greatly amplified cardiovascular disease resulting in death either myocardial infarction or stroke. Although the average life expectancy in HGPS is 13 years (range of 7-27 years),  our patient lived until 22 years. A study found that the accelerated atherosclerosis in HGPS is similar in cardiovascular histopathology to geriatric patients, although with more prominent adventitial fibrosis. 
The accelerated atherosclerosis, an integral feature of HGPS, might have resulted in hypertension, ischemic cardiomyopathy and left ventricular failure in our patient. Our patient manifested most of the quintessential clinical features of HGPS such as high-pitched voice, short stature and low weight for height, incomplete sexual maturation (low testicular volume and features of hypogonadism), generalized osteoporosis, crowded dentition and hypertension. There was restrictive lung disease from rib crowding/chest wall deformity and interstitial lung disease, which may explain his type II respiratory failure, PAH and right heart failure. He also displayed the classical low HDL with other lipid parameters being normal (which may have played a role in the accelerated atherosclerosis). Elevated prothrombin time and thrombocytosis described in our patient are also commonly reported. Skin and underlying muscle atrophy, osteoporosis, arthritis, poor growth, and alopecia were a few other cardinal features that our case featured.
Histopathologically HGPS patients may show marked loss of vascular smooth muscle cells within the great vessels, arteries, and arterioles associated with sclerosis, fibrosis and narrowing of the lumen.  Imaging studies may show diffuse osteopenia, fish mouthed vertebral bodies, widened metaphyses, epiphyseal overgrowth, and narrow diaphyses and acroosteolysis (distal bone resorption) of the phalanges and distal clavicles (all found in our patient). In addition there may be Coxa valga and avascular necrosis of the femoral head.
Although no standard therapy is available currently to treat HGPS, supportive management with low-dose aspirin, physical and occupational therapy, hydrotherapy (joints and arthritis), adequate nutritional intake via a gastrostomy tube with high protein supplements may make some difference in the quality of life. Growth hormone,  rapamycin (in experimental models)  and farnesyl transferase inhibitors (FTIs)  have all shown some benefit in various studies. A combination of FTIs with pravastatin and zoledronic acid is currently being investigated and has fruitful effects so far. 
| Conclusion|| |
Early diagnosis, supportive therapy with physiotherapy and anti-platelet drugs and statins and early initiation of specific therapies targeted against cardiovascular and cerebrovascular morbidity form the cornerstone of management in HGPS.
| Acknowledgment|| |
We thank our colleagues and staff of Internal medicine. Author thank the patient for providing consent to use clinical photographs.
| References|| |
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[Figure 1], [Figure 2]