Introduction: Wolman Disease [WD] is a rare, autosomal recessive disease caused by lysosomal acid lipase deficiency and characterized by accumulation of cholesterol-esters and triglycerides primarily in the liver and spleen. Patients present within the first year of life with a rapidly progressive disease.
Case: A girl born to consanguineous parents was diagnosed with WD due to characteristic manifestations and family history (genetically confirmed). At the age of 2 months (ms) she underwent allogeneic cord blood transplantation (SCT) with conditioning therapy of TBI, antithymocytic globulin & Cytoxan. The girl continued follow-up for 16 years (yrs) at a single center.
Growth: At 5yrs, she underwent growth hormone (GH) stimulation testing due to short stature (height −2.4s.d.), with normal GH secretion. Due to continued growth deceleration (height −3.1s.d.) at the age of 7.5yrs, GH axis was reassessed with normal response. IGF-1 levels were mildly elevated with continuous increase above +2SD over time. All other pituitary hormones were normal. OGTT showed normal GH suppression. IGF-1 receptor gene analysis revealed a novel heterozygous benign variant. By 14yrs, final height was reached (−4.5s.d.) and IGF-1 levels normalized spontaneously.
Puberty: Adrenarche started at the age of 9.6yrs, gonadarche started 8ms later and proceeded spontaneously despite elevated FSH and low AMH levels. She had menarche at the age of 11.4yrs with regular menses since then. At the age of 15.7yrs, AMH levels were sub-normal, with a decrease in FSH levels to normal range.
Thyroid: Immediately after BMT, she developed hypothyroidism and was treated with thyroxin replacement.
Adrenal: Normal response of cortisol post standard-dose ACTH stimulation tests at diagnosis and throughout follow-up.
Metabolic: BMI was constant at the 50th percentile. OGTT at 10.4yrs demonstrated impaired glucose tolerance. After completion of puberty, we observed continued elevation of HbA1c levels up to 6.6% (normal 4.65.7%) with impaired fasting glucose, impaired glucose tolerance and hyperinsulinemia. At the age of 12yrs, she developed hypertriglyceridemia. At the age of 13.5yrs she was diagnosed with non-alcoholic fatty liver. Metformin treatment with dietary changes partially improved HbA1c levels (6.2%), hypertriglyceridemia and non-alcoholic fatty liver disease.
Conclusion: WD is a rare disease. We present long term follow-up of a girl with WD treated with SCT at the age of 2ms, formerly presented at the age of 4yrs with only hypothyroidism. Continuous follow-up for more than 16yrs revealed significant endocrine and metabolic consequences. We recommend continued follow-up for development of endocrine and metabolic complications.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology