A five year old female presented, shortly after migration from Africa, with chronic scalp infection and otitis media. She was noted to have symptomatic hyperglycaemia, with a history dating back possibly to two years of age. She was observed to have several cutaneous and facial features typical of the RMS phenotype (Figure 1).
Biochemical insulin resistance was documented, with elevated fasting plasma insulin level of 1836 pmol/L (normal laboratory value: 9-80 pmol/L). At age six, diabetes mellitus was diagnosed with the classical pattern of daytime postprandial hyperglycaemia, but paradoxical nocturnal fasting hypoglycaemia. Genetic testing demonstrated a homozygote mutation at position 119 of the mature alpha subunit of the insulin receptor, but a normal beta subunit. She is of African ethnicity, and was born of a consanguineous union between first cousins. There is no other family history of insulin resistance.
Her diabetes was initially managed with Metformin (currently 3 grams/day) followed by a brief trial of added pioglitazone. She rapidly progressed to insulin, with a current insulin requirement of 2100 units per day (>50 units/kg/day). Despite this, her glycaemic control remains suboptimal, with an HbA1c of 75 mmol/mol (9%). She has a current weight of 36 kg, height of 148 cm (Z score -1.1) and BMI of 16.6 kg/m2.
Enlarged kidneys were noted from six years of age. Ultrasonography revealed persistent renal sizes greater than two standard deviations for her age (11 cm diameter left, 10 cm diameter right), with poorly defined medullary renal pyramids, loss of normal cortico-medullary differentiation, and a mildly dilated right collecting system. There were no renal cysts or duplex system. Nephrocalcinosis was identified, and appropriate biochemical studies were done, revealing hypercalciuria (Table 1). At age of eight years a mercaptoacetyl triglycine MAG 3 renogram demonstrated normal function bilaterally with an effective renal plasma flow (ERPF) from right kidney of 379 mL/min and left kidney of 404 mL/min (normal ERPF>300 ml/min).
At the age of eleven years she presented with recurrent left flank pain, associated microscopic haematuria, and albuminuria on dipstick examination. There were no features to suggest an infective or traumatic aetiology to her symptoms. She was pre-pubertal. Ultrasonography showed a right kidney of 12.3 cm, left kidney of 13.2 cm, with multiple bilateral renal calculi, the largest 10mm in diameter. The right renal pelvis was dilated (1.2 cm), and a simple 10 mm cyst seen in the left kidney. The bladder was normal. A CT urogram revealed a 2 mm calcification seen to the left of the true renal pelvis, suggestive of an intraluminal ureteric calculus. Intravenous pyelogram further demonstrated paintbrush-like appearances of the renal pyramids, consistent with MSK (Figure 2). The patient had the most severe form of MSK, grade 4, with involvement of all the calyces in both kidneys.
Her nephrocalcinosis was actively managed by optimising fluid intake and a trial of thiazide diuretic. Treatment was ceased at 3 months, at the request of the family as she remained asymptomatic from her nephrocalcinosis. No further acute episodes of nephrocalcinosis or pain have recurred.