Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2019) 7 P112 | DOI: 10.1530/boneabs.7.P112

ICCBH2019 Poster Presentations (1) (226 abstracts)

Case report: investigation of an osteolytic lesion leading to the diagnosis of congenital generalized lipodystrophy due to a novel AGPAT2 mutation

Avivit Brener 1, , Erella Elkon-Tamir 1, , Leonid Zeitlin 2, & Yael Lebenthal 1,

1Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children’s Hospital, Tel Aviv, Israel; 2Pediatric Orthopedic Department, Dana-Dwek Children’s Hospital, Tel Aviv, Israel; 3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Osteolytic lesions can be the presenting manifestation of various medical conditions, including bone tumors (benign and malignant) and infectious and endocrine diseases.

Presenting problem: A 19-year-old Bedouin male from a consanguineous family was referred to our medical center for orthopedic consultation due to a pathological fracture and a cystic lesion in his right ulna. A skeletal survey revealed another cystic lesion in the left tibia. A SPECT bone scan ruled out additional bone pathology. A bone biopsy revealed normal cortical bone with no evidence of malignancy. During hospitalization he was referred for endocrine evaluation due to poorly controlled diabetes.

Clinical management: Physical examination revealed prominent muscles, an acromegaloid appearance, marked acanthosis nigricans, and skin papillomatosis. Anthropometric measurements: height 170 cm, weight 77.2 kg, and BMI 26.3 kg/m2. Body composition (bioelectrical impedance scale): 13% fat (normal range 10–20%), muscle mass 63.6 kg (49.7–63 kg), normal estimated bone mass 3.3 kg, basal metabolic rate 2000 kcal, and a muscular physique.

Laboratory evaluation: Diabetes with severe insulin resistance (fasting glucose 189 mg/dl [10.5 mmol/l], fasting insulin 70.95 μu/ml, HOMA-IR 33). Comorbidities: dyslipidemia with mildly elevated triglycerides 177 mg/dl (elevated ≥150 mg/dl), and low high-density lipoprotein 29 mg/dl (normal in males >40 mg/dl), non-alcoholic fatty liver disease – hepatic fat deposition with moderate fibrosis, and microalbuminuria. There was no evidence of heart disease. The clinical phenotypic features were highly suggestive of congenital generalized lipodystrophy due to AGPAT2 mutation. Undetectable serum leptin levels supported this diagnosis. Next-Generation Sequencing targeting the AGPAT2 gene identified a novel homozygous frameshift mutation. Deterioration of glycemic control with progressive increase in insulin requirements to 7 Units/kg per day led to initiation of metreleptin (recombinant human methionyl leptin). Leptin replacement therapy, the only medication approved specifically for lipodystrophy, resulted in a remarkable improvement in glycemic control and reduction in insulin requirements, with no change in the osteolytic long bone lesions.

Discussion: Congenital generalized lipodystrophy syndromes comprise a rare, heterogeneous group of conditions characterized by a distinctive muscular physique. Osteolytic lesions in long bones in the context of lipodystrophy point towards the diagnosis of AGPAT2 gene mutations. The precise diagnosis enables the clinician to avoid unnecessary invasive procedures and provide appropriate management.

Disclosure: The authors declared no competing interests.

Volume 7

9th International Conference on Children's Bone Health


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