Severe Pressure Ulcers in Two Patients With Adrenoleukodystrophy

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TL;DR

This case report describes two male patients with adrenoleukodystrophy (ALD) who developed severe pressure ulcers with bone exposure in the pelvic region and feet, a complication not previously reported in ALD. Both patients had immobility, incontinence, and poor nutrition, which contributed to ulcer formation; one patient died from bronchopneumonia at age 31. The findings highlight that ALD patients with progressive neurological decline are at high risk for severe pressure ulcers, warranting early multidisciplinary preventive care.

Full summary

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**Background:** Adrenoleukodystrophy (ALD) is a rare X-linked disorder caused by pathogenic variants in the ABCD1 gene, leading to impaired peroxisomal beta-oxidation and accumulation of very long-chain fatty acids (VLCFAs). ALD presents with four primary phenotypes: cerebral ALD, adrenomyeloneuropathy (AMN), Addison's disease, and female ALD. Patients experience progressive spastic paraplegia, sensory disturbance, cognitive deterioration, adrenocortical insufficiency, and bladder/bowel abnormalities. Although these symptoms place patients at high risk for pressure ulcers, this complication has never been formally reported in the ALD literature.

**Methods:** This is a case report of two male patients with genetically confirmed ALD who presented with severe pressure ulcers. Both patients underwent clinical examination, laboratory testing (including VLCFA analysis, ACTH, cortisol), MRI imaging, and genetic testing via next-generation sequencing and Sanger sequencing of the ABCD1 gene. Patient 1 also underwent SPAST gene sequencing due to a family history of spastic paraplegia.

**Key Results:** Patient 1 was a 27-year-old male with adolescent cerebral-type ALD who presented with septic shock (temperature 39.4°C, BP 73/51 mmHg, pulse 129 bpm) and deep pressure ulcers with black necrotic tissue and abscess formation on the sacral and bilateral greater trochanter regions. Laboratory findings showed severe inflammation (CRP 22.7 mg/dL, procalcitonin 8.27 ng/mL, WBC 19,370/μL) and hypoalbuminemia (albumin 1.5 g/dL). Blood and tissue cultures grew Proteus mirabilis. He had elevated ACTH (135.2 pg/mL), low cortisol (2.0 μg/dL), and elevated C26/C22 VLCFA ratio (0.072; reference 0.007–0.017). Genetic testing revealed a hemizygous likely pathogenic variant in ABCD1 (c.892G>A, p.Gly298Ser) and a heterozygous variant of uncertain significance in SPAST (c.815T>C, p.Leu272Ser). Brain MRI showed symmetric posterior deep white matter lesions with gadolinium enhancement at the margins. Despite treatment with meropenem, norepinephrine, and surgical debridement, he developed septic arthritis of the left hip requiring two arthrotomies. Ulcers eventually became scar tissue over 13 months, but his cognitive function declined further, and he died at age 31 from respiratory failure due to bronchopneumonia.

Patient 2 was a 64-year-old male with the AMN phenotype who presented with fever (39.2°C), dehydration, and deep pressure ulcers with black necrotic tissue on the sacral, bilateral lateral malleus, and left lateral heel regions. He had a 5 cm bullae on both heels that had ruptured. Laboratory findings showed inflammation (CRP 13.2 mg/dL, WBC 12,400/μL) and hypoalbuminemia (albumin 2.1 g/dL). ACTH (56.6 pg/mL) and cortisol (8.8 μg/dL) were within normal limits, but the C26/C22 VLCFA ratio was elevated (0.057). He had the same ABCD1 p.Gly298Ser variant but no SPAST variant. Spinal MRI showed thoracic and lumbar spinal cord atrophy; brain MRI was normal. Nerve conduction studies showed absent compound motor action potentials and sensory nerve action potentials in the lower extremities. He was treated with meropenem and surgical debridement; foot ulcers epithelialized after 3 months, and the sacral ulcer required negative pressure wound therapy (NPWT) and healed after 8 months.

**Clinical Implications:** This is the first report identifying severe pressure ulcers as a complication of ALD. The authors hypothesize that immobility from progressive neurological deterioration, poor nutrition, urinary/fecal incontinence, and loss of pain perception due to cerebral and spinal involvement all contribute to pressure ulcer development. In patient 1, cognitive withdrawal and psychiatric symptoms exacerbated immobility; in patient 2, inadequate caregiving after his father's death was a contributing factor. The co-occurrence of SPAST and ABCD1 variants in patient 1 and his mother initially led to a misdiagnosis of SPG4 (hereditary spastic paraplegia type 4), delaying ALD diagnosis and corticosteroid therapy. The authors emphasize that ALD should be considered in male patients with progressive spastic paraplegia, especially when accompanied by elevated ACTH, skin pigmentation, or abnormal VLCFA ratios. Proactive identification of ALD patients and early multidisciplinary intervention—including wound care, nutritional support, incontinence management, and caregiver education—are essential to prevent the development of severe, life-threatening pressure ulcers.