LBODP030 A Rare Case Of Partial Lipodystrophy From Mpdl (mandibular Hypoplasia, Deafness, Progeroid, Lipodystrophy Syndrome) Due To Pold1 Gene Mutation
Authors: Majumdar Sujoyeeta , Gaba Ruchi , Ram Nalini , Force Bahar Kapoor 
Published: November 2022

MDPL (Mandibular hypoplasia, Deafness, Progeroid, Lipodystrophy syndrome) caused by a mutation in the polymerase delta 1 (POLD1) gene is an extremely rare progeroid syndrome associated with partial lipodystrophy. Currently, there are about 24 cases reported worldwide(1), mostly in people of European descent. We are reporting one such rare case in a Hispanic patient. The patient is a 37 year old male from Honduras who was referred to us by genetics for diabetes management. Family members noted extremely thin limbs and he did not walk till 2 years of age. Family history was negative with 8 full siblings, all reportedly healthy. On examination, his BMI was 15.19 kg/m2. He was noted to have birdlike facies with mid-face hypoplasia, beaked nose, retrognathia, dental malocclusion, and protruding maxillary teeth. He also had bilateral proptosis. His extremities were thin, lacking subcutaneous fat and muscle bulk with distal joint contractures in elbow, hands and feet. Genitourinary showed low testicular volumes (&lt;3 ml). Genetic testing revealed a recurring mutation in the active site of POLD1 gene, which is diagnostic for MDPL. His clinical presentation was classic with dysmorphism, deafness, lipodystrophy and metabolic abnormalities. Due to the rarity of the disorder, there is very limited data on management of these patients. A symptom-based management was recommended. In terms of his diabetes, it was diagnosed at age 33 when his HbA1c was 11.2 and he was started on insulin. Patients with this syndrome tend to have insulin resistance. C-peptide was 2.88 ng/ml (ref. range: 0.78 - 5.19 ng/mL) with glucose 160 mg/dL indicating adequate beta-cell reserve; GAD-65 and anti-pancreatic islet cell antibodies were negative. Insulin was weaned off and currently, his diabetes is being managed with diet and lifestyle changes. He was found to have elevated total cholesterol and triglycerides. Hepatic steatosis was seen on liver ultrasonography. He was started on fenofibrate and low-fat diet; lipid panel has normalized. His echocardiogram was normal. In addition, males are known to have hypogonadotropic hypogonadism however this patient had a low testosterone and high FSH and LH, indicative of primary hypogonadism. A scrotal ultrasound was ordered. DXA scan showed low bone mineral density with the lowest Z-score of -3.6 at the lumbar spine. He was started on testosterone replacement with Vitamin D. Testosterone therapy will help replace the testosterone deficiency in addition to slowing down bone loss. MDPL syndrome is an exceedingly rare clinical entity associated with multiple endocrinopathies. We plan to periodically monitor labs and imaging to continue managing this patient with a symptom-based approach. (1) Wang, Xiu-Wen; Lu, Ling-Yun; Xie, Ying1; Yu, Xi-Jie1 A Chinese girl with (MDPL) diagnosed via POLD1 mutation detection, Chinese Medical Journal: August 20, 2020 - Volume 133 - Issue 16 - p 2009-2011

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