Low Bone Mineral Density in a Patient with Atypical Progeria Syndrome: A Case Report

Presentation Number: SUN 318
Date of Presentation: April 2nd, 2017

Megan Crawford* and Leila Zeinab Khan
Cleveland Clinic, Cleveland, OH


Background: Hutchinson-Gilford Progeria syndrome (HGPS) is an autosomal dominant syndrome caused by a heterozogous de novo point mutation in codon 608 of exon 11 Lamin A/C (LMNA) gene that is extremely rare with estimated frequency of 1 in 8 million live births (1) . Atypical forms of the disease, termed atypical progeria syndromes (APS) are even less frequent and are characterized by heterogeneous phenotypic presentation and clinical course with certain discrete features from HGPS. While accelerated progression to osteoporosis has been described in HGPS, the presence of premature metabolic bone disease in APS is varied.

Clinical Case: We describe a 24 year old Caucasian male with a diagnosis of atypical progeria syndrome who presented to our clinic for evaluation of low bone density on bone densitometry (DXA). The patient was diagnosed with APS at age 8 years of age, he began to show signs of failure to thrive with progeroid features including micrognathia/retrognathia, prominent eyes, drooping shoulders and short stature. Subsequent genetic analysis revealed a novel missense mutation in exon 1 of the LMNA gene resulting in p.Gly111Lys amino acid change (2). As part of research protocol at an outside institution, the patient had DXA done at age 16 which revealed low bone density expected for age with a Z score of -3.2 at the left femoral neck and Z score of -3.1 in the lumbar spine. Calcium and vitamin D supplementation was initiated. The patient later had three episodes of calcium oxalate renal stones and calcium supplementation was discontinued. The patient’s only noted fracture to date was a heel stress fracture after landing on his heel subsequent to slipping down stairs around age 14. At the time of presentation to our clinic, the patient was 5’5” tall and weighed 95 lb (BMI: 16.03 kg/m2) noting stable weight over the past year. The patient’s exam at follow-up in our clinic also revealed pectus excavatum, prominent front teeth, large nose, and a grade 5/6 systolic murmur secondary to severe aortic stenosis with moderate aortic regurgitation. He was undergoing evaluation by cardiology for aortic valve replacement at the time of the visit. Other notable findings on workup during our evaluation included an elevated TSH at 9.30 (N:0.40-5.50 µU/mL), borderline 25-hydroxyvitamin D of 31.3 (N: 31-80 ng/mL), PTH 23 (N:25-65 pg/mL), total testosterone 282 (N: 220-100 ng/dL), HbA1C of 4.8% (N<5.6%), negative Celiac screening, and normal C-telopeptide of type 1 collagen (CTX) of 33.2 (N: 21.9 - 75.0 nM/mM Creat). The patient was started on levothyroxine 50 mcg daily and recommended to take 2000 IU vitamin D3 daily.

Conclusion: The course of APS due to mutation in exon 1 of the LMNA gene leading to p.Gly111Lys, which has solely been reported in our patient to date, involves accelerated bone density loss for age, valvulopathy and hypothyroidism in early adulthood.


Nothing to Disclose: MC, LZK