Endocrine Abstracts

Introduction: Early onset diabetes mellitus and poor glycaemic control can predispose to various long-term complications. NICE recommends regular assessment starting at 12 years of age to diagnose micro/macro vascular complications and neuropathy for appropriate management. Rare undiagnosed metabolic disorders could pose diagnostic and management challenges. We report an unusual presentation of a rare metabolic disorder in an adolescent with type-1 diabetes mellitus (T1D).

Case report: A 14-year-old boy with early onset diabetes at 18 months of age presented with abdominal pain, hepatomegaly and weight loss (Weight SDS −4.3, Height SDS −2.9). Hepatological assessment showed deranged transaminases (ALT & AST elevated up to 150–250 IU/l) and hypercholesterolaemia (total cholesterol >9.5 mmol/l & LDL >6 mmol/l) but normal screening bloods for common liver disorders. The liver biopsy showed fatty infiltration suggestive of steatohepatitis.

Over the next 3 years he was admitted with multiple DKA episodes precipitated by infections including recurrent axillary abscesses requiring surgical interventions. During these episodes he was noted to have very high transaminases (ALT >1000, AST > 4000 IU/l) and persistently high lactate levels (4–8 mmol/l). Interestingly the transaminase levels improved quickly whenever DKA/infection resolved. Urine organic acid analysis revealed 3-methylglutaconic aciduria. A mitochondrial respiratory chain study in muscle was normal and exome sequencing did not reveal any mutation in the genes related to mitochondrial disorders.

Subsequently he developed severe burning sensation and electric shock like shooting pain in his lower limbs suggestive of peripheral neuropathy. His deep tendon reflexes and sensory assessment using monofilament were normal. Serum B₁₂ and folate levels and thyroid function tests were normal. Doppler of his lower limbs was normal and his symptoms were managed with Pregabalin and Amitriptyline with limited success. Echocardiogram revealed mild ventricular hypertrophy. The constellation of clinical features including peripheral neuropathy, steatohepatitis, hepatomegaly, cardiac hypertrophy and methyl glutaconic aciduria points towards a new genetic/metabolic syndrome related to diabetes mellitus.

Conclusion: The case illustrates the importance of investigating for underlying rare metabolic disorders in patients with T1D presenting with recurrent episodes of DKA and lactic acidosis.