Lost bones: differential diagnosis of acro-osteolysis seen by the pediatric rheumatologist

Limenis, Elizaveta; Stimec, Jennifer; Kannu, Peter; Laxer, Ronald M.

doi:10.1186/s12969-021-00596-0

Cited by 13 publications

(8 citation statements)

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“…These findings fulfilled the diagnostic criteria of acro‐osteolysis, a type of “vanishing bone” status, on the fingertip that may be caused by heterogeneous disorders, including hormonal alterations, ischemia, traumatic changes, and neurological disorders. [ 10,11 ] However, in addition to the acro‐osteolysis, we noticed the patient had multiple osteolytic lesions in other parts of the fingers (Fig. 1 B ).…”

Section: Resultsmentioning

confidence: 95%

Identification of a Biallelic Missense Variant in Gasdermin D (c.823G > C, p.Asp275His) in a Patient of Atypical Gorham‐Stout Disease in a Consanguineous Family

et al. 2023

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Gorham–Stout disease (GSD), also called vanishing bone disease, is a rare osteolytic disease, frequently associated with lymphangiomatous tissue proliferation. The causative genetic background has not been noted except for a case with a somatic mutation in KRAS. However, in the present study, we encountered a case of GSD from a consanguineous family member. Whole‐exome sequencing (WES) analysis focusing on rare recessive variants with zero homozygotes in population databases identified a homozygous missense variant (c.823G > C, p.Asp275His) in gasdermin D (GSDMD) in the patient and heterozygous in his unaffected brother. Because this variant affects the Asp275 residue that is involved in proteolytic cleavage by caspase‐11 (as well as ‐4 and ‐5) to generate an activating p30 fragment required for pyroptotic cell death and proinflammation, we confirmed the absence of this cleavage product in peripheral monocytic fractions from the patient. A recent study indicated that a shorter p20 fragment, generated by further cleavage at Asp88, has a cell‐autonomous function to suppress the maturation of osteoclasts to resorb bone matrix. Thus, the present study suggests for the first time the existence of hereditary GSD cases or novel GSD‐like diseases caused by GSDMD deficiency. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Section: Resultsmentioning

confidence: 95%

Identification of a Biallelic Missense Variant in Gasdermin D (c.823G > C, p.Asp275His) in a Patient of Atypical Gorham‐Stout Disease in a Consanguineous Family

et al. 2023

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“…Acro-osteolysis, a symptom of PHO, was also observed in our case. A reasonable theory is that chronically elevated levels of PGE2 due to HPGD deficiency lead to limb bone ablation by stimulating osteoclast activity on the one hand and bone resorption through the promotion of vascular endothelial growth factor (VEGF) ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Novel homozygous HPGD variant leads to primary hypertrophic osteoarthropathy with intussusception and acro-osteolysis in a Chinese family

Liu¹,

Wu²,

Tang³

et al. 2023

Front. Pediatr.

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ObjectiveTo perform molecular genetic analysis of a patient diagnosed with primary hypertrophic osteoarthropathy (PHO) with malnourishment, intussusception, and acro-osteolysis.Case presentationAt the age of 7 years, a boy born to a consanguineous couple was diagnosed with PHO attributed to delayed closure of the cranial suture, eczema, clubbing of fingers, and swelling of the knee and ankle. Clinical characteristics and follow-up data for 3 years were collected and analyzed. Trio whole-exome sequencing (WES) and copy number variant sequencing were used to screen for causative genetic variants. Candidate variants of the patient and his parents were confirmed by Sanger sequencing. When he was 7 years old, trio WES found that he had biallelic novel variants c.498 + 1G > A, inherited from his parents, in the HPGD gene. The patient was markedly malnourished. Ultrasonography and computed tomography showed intussusception with a gradual expansion of the duodenum, localized intestinal wall thickening, and acro-osteolysis. Cross-sectional blood tests showed that the patient had continuously decreased levels of serum 25-hydroxy vitamin D and serum ferritin at the age of 7and 10 years.ConclusionPHO due to HPGD defects is rare in pediatric patients, and finding homozygous novel c.498 + 1G > A has expanded the spectrum of causative variants of HPGD and provided a clue for genotype-phenotype correlation analysis. Similar to mouse model results, human HPGD deficiency may also cause abnormal digestive tract development, and related secondary vitamin D deficiency and acro-osteolysis should be considered in HPGD-related PHO.

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“…Three patients described by Gray et al presented AO, cortical irregularity of long bones and metadiaphyseal enchondromatosis [ 18 ]. Recently Limenis et al published a review on differential diagnosis of AO and its distinguishing features, with particular attention paid to types more commonly encountered in paediatrics [ 21 ]. Our article reports new findings on the relationship between this amplification and this disease expressed by an AO and an anomaly of the long bones.…”

Section: Discussionmentioning

confidence: 99%

Is an association of acro-osteolysis, bone fragility, and enchondromatosis a newfound disease caused by an amplification of PTHLH? A case report

et al. 2022

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Background Acro-osteolysis (AO) refers to resorption of the distal finger and toe phalanges. It displays two patterns: (i) diffuse AO and (ii) transverse or bandlike AO. AO can be a sign of local distress (e.g. of toxic origin), but is very often a sign of a constitutional or systemic acquired disorder. Case presentation A 15-year-old girl was referred to a paediatric rheumatologist for recurrent pain in her fingertips. She presented a particular cross-sectional AO associated with the presence of intraosseous cysts and bone fragility with atypical fractures. Initial laboratory tests and radiological examination did not allow an etiological diagnosis. Genetic studies revealed a 12p11.22-p11.23 microduplication of 900 kb including the PTHLH (parathyroid hormone-like hormone) gene, which encodes for a hormone involved in the regulation of endochondral ossification and differentiation of chondrocytes, via its PTHLH receptor. Conclusions To date, 12p11.22-p11.23 duplications have been reported in five families with skeletal abnormalities, and in particular AO and enchondromatosis associated with bone fragility. This new observation, added to the other reported cases, suggests a close relationship between the presence of this microduplication and the skeletal abnormalities found in the patient. We suggest the descriptive name ABES (acro-osteolysis, bone fragility and enchondromatosis syndrome) to designate this disorder.

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Lost bones: differential diagnosis of acro-osteolysis seen by the pediatric rheumatologist

Cited by 13 publications

References 50 publications

Identification of a Biallelic Missense Variant in Gasdermin D (c.823G > C, p.Asp275His) in a Patient of Atypical Gorham‐Stout Disease in a Consanguineous Family

Identification of a Biallelic Missense Variant in Gasdermin D (c.823G > C, p.Asp275His) in a Patient of Atypical Gorham‐Stout Disease in a Consanguineous Family

Case report: Novel homozygous HPGD variant leads to primary hypertrophic osteoarthropathy with intussusception and acro-osteolysis in a Chinese family

Is an association of acro-osteolysis, bone fragility, and enchondromatosis a newfound disease caused by an amplification of PTHLH? A case report

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