Metabolic and other morbid complications in congenital generalized lipodystrophy type 4.

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.

Bone marrow granuloma in typhoid Fever: a morphological approach and literature review.

Typhoid fever is one of the few bacterial infections in humans where bone marrow evaluation is routinely recommended. However, the morphological aspect of typhoid fever in bone marrow has been rarely described in the literature. We describe a 25-year-old male patient who presented with prolonged fever suspected to be of tubercular etiology. Bone marrow examination showed well-formed histiocytic and epithelioid granulomas and erythrophagocytosis; and the bone marrow aspirate culture grew Salmonella typhi A. In view of potential clinical implications, typhoid fever should be considered as a differential diagnosis to tuberculosis in the evaluation of prolonged fever; especially in high prevalent areas. We suggest that erythrophagocytosis may serve as a morphological marker in typhoid granulomas in the bone marrow; and bone marrow culture should be submitted in every suspected case for appropriate patient management.