Case Quiz (May 2025)

A 9-y-old girl, the only child of non-consanguineous parents, with no relevant family history presented with abnormal urinalysis test. Her developmental milestones were normal. Her past medical history was largely unremarkable, except for consistently being in the lower percentiles for growth and episodes of nausea, vomiting and occasional diarrhea after taking heavy protein meals.

A routine urinalysis revealed microscopic hematuria, proteinuria, and mild glycosuria. An abdominal ultrasound showed hyperechogenic renal cortex and splenomegaly. Further investigations indicated impaired renal function, nonselective proteinuria, elevated urinary beta2-microglobulin levels, and tubular dysfunction. Her venous blood gases revealed compensated metabolic acidosis. Apart from mild degree of hypokalemia and hypophosphatemia, all electrolytes were normal.

Additional laboratory findings included thrombocytopenia, borderline normal hemoglobin, elevated lactate dehydrogenase (LDH), hypertriglyceridemia, hyperferritinemia, and intermittently elevated transaminases. Renal biopsy findings was non-significant.

Protein distribution in granulocytes on peripheral blood smear ruled out MYH9-related disorders. Genetic testing for hereditary amyloidosis with primary renal involvement, Dent disease type 1, and a panel of 94 genes associated with proteinuric nephropathies yielded negative results.

A definitive diagnostic test was done.

Case Answer (May 2025)

    Lysinuric protein intolerance (LPI)
LPI is a rare inherited metabolic disorder caused by autosomal recessive pathogenic variants in the SLC7A7 gene. It exhibits wide clinical variability without a clear genotype–phenotype correlation. The underlying defect leads to a shortage of substrates required for normal hepatic urea cycle function, resulting in chronic protein aversion and postprandial drowsiness after protein-rich meals. Over time, this contributes to malnutrition, failure to thrive, osteoporosis, and an acute risk of postprandial hyperammonemia with potential neurological complications.

Renal involvement is a common manifestation of LPI. The earliest indicator is often isolated mild proteinuria. Proximal tubular dysfunction (Fanconi syndrome) and associated proximal renal tubular acidosis can lead to hypercalciuria and nephrocalcinosis. Elevated urinary β2-microglobulin is observed in approximately 90% of patients. Histological findings may include isolated nephrocalcinosis, chronic tubulointerstitial nephritis, diffuse membranoproliferative glomerulonephritis, and glomerular amyloidosis.