Mitochondrial Disease (MELAS Syndrome) Discovered at the Start of Pregnancy in a Patient with Advanced CKD: A Clinical and Ethical Challenge

Abstract

Pregnancy is a challenge in the life of a woman with chronic kidney disease (CKD), but also represents an occasion for physicians to make or reconsider diagnosis of kidney disease. Counselling is particularly challenging in cases in which a genetic disease with a heterogeneous and unpredictable phenotype is discovered in pregnancy. The case reported regards a young woman with Stage-4 CKD, in which “Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes” (MELAS syndrome), was diagnosed during an unplanned pregnancy. A 31-year-old Caucasian woman, being followed for Stage-4 CKD, sought her nephrologist’s advice at the start of an unplanned pregnancy. Her most recent data included serum creatinine 2–2.2 mg/dL, Blood urea nitrogen (BUN) 50 mg/dL, creatinine clearance 20–25 mL/min, proteinuria at about 2 g/day, and mild hypertension which was well controlled by angiotensin-converting enzyme inhibitors (ACEi); her body mass index (BMI) was 21 kg/m2 (height 152 cm, weight 47.5 kg). Her medical history was characterized by non-insulin-dependent diabetes mellitus (at the age of 25), Hashimoto’s thyroiditis, and focal segmental glomerulosclerosis. The patient’s mother was diabetic and had mild CKD. Mild hearing impairment and cardiac hypertrophy were also detected, thus leading to suspect a mitochondrial disease (i.e., MELAS syndrome), subsequently confirmed by genetic analysis. The presence of advanced CKD, hypertension, and proteinuria is associated with a high, but difficult to quantify, risk of preterm delivery and progression of kidney damage in the mother; MELAS syndrome is per se associated with an increased risk of preeclampsia. Preterm delivery, associated with neurological impairment and low nephron number can worsen the prognosis of MELAS in an unpredictable way. This case underlines the importance of pregnancy as an occasion to detect CKD and reconsider diagnosis. It also suggests that mitochondrial disorders should be considered in the differential diagnosis of kidney impairment in patients who display an array of other signs and symptoms, mainly type-2 diabetes, kidney disease, and vascular problems, and highlights the difficulties encountered in counselling and the need for further studies on CKD in pregnancy.