L-Carnitine, an amino acid derivative critical for fatty acid metabolism, exhibits anti-inflammatory, antioxidant, and cytoprotective properties, with emerging applications in dermatology. This review explores its therapeutic potential, both topically and systemically, and its role as a biomarker in various skin disorders. A systematic search of Medline, EMBASE, and PubMed (1946-January 2025) was conducted, focusing on L-carnitine and dermatologic conditions, excluding acetyltransferases, acyltransferases, breast, and genetic metabolic diseases. From 420 articles, 59 were included after screening in Covidence. Data on study design, sample size, carnitine type, and outcomes were extracted and validated by two authors. Topically, L-carnitine (1%-5%) reduces acne lesions, sebum production, post-inflammatory hyperpigmentation, and cellulite, particularly when combined with agents like licochalcone-A or salicylic acid. Systemic L-carnitine mitigates inflammation, oxidative stress, and treatment-related side effects (eg, from corticosteroids, isotretinoin, vismodegib) while improving skin elasticity, microcirculation, wound healing, and fibrosis in conditions like Raynaud's disease, venous leg ulcers, and sclerotic disorders. As a biomarker, altered carnitine levels and metabolites reflect disease mechanisms in genodermatoses (eg, restrictive dermopathy, recessive dystrophic epidermolysis bullosa), inflammatory dermatoses, and melanoma, aiding diagnosis and monitoring. L-Carnitine shows promise as a therapeutic and diagnostic tool in dermatology, with benefits in acne, sebum control, post-inflammatory hyperpigmentation, cellulite, inflammation, and tissue repair. Its biomarker potential enhances disease insights and personalized care. Further dermatology-specific trials are needed to optimize dosing, formulations, and long-term safety, particularly regarding trimethylamine-N-oxide-related cardiovascular risks.

Restrictive Dermopathy (RD, OMIM #275210) is an ultra-rare, lethal genodermatosis caused by defects in lamins and related proteins. RD is caused by biallelic pathogenic variants in ZMPSTE24, which encodes zinc metallopeptidase ZMPSTE24, an enzyme essential for processing prelamin A, the precursor of lamin A. While null variants leading to a total loss of prelamin A processing have been related to neonatally lethal RD, variants preserving residual prelamin A processing function cause an allelic disorder called Mandibuloacral Dysplasia Type B (MAD-B). RD is characterized by taut translucent skin, visible superficial vessels, joint contractures, and dysmorphic features, with death usually occurring within the first month of life. Cardiac anomalies, including ASD and PDA, have been reported in a few patients, most of whom were not genetically confirmed, and transposition of the great arteries (TGA) has been described only once, also without molecular confirmation. We report a patient with restrictive dermatopathy (RD) presenting with double outlet right ventricle (DORV) and pulmonary valve atresia which have not been previously reported in association with RD. Exome Sequencing (ES) was performed, revealing a novel homozygous splice-site variant in ZMPSTE24 (c.1203 + 1G>T). Segregation analysis was performed in the mother and two siblings. To our knowledge, DORV has not previously been reported in an RD patient. This case expands the genotypic spectrum of RD and suggests a possible link with complex cardiac malformations.

Restrictive dermopathy (RD) is a rare, lethal, congenital autosomal recessive laminopathy syndrome characterized by generalised tight translucent skin, dysmorphic facies, arthrogryposis multiplex congenita, and pulmonary hypoplasia. It is caused by mutations in either ZMPSTE24 or LMNA. Variants in these genes, which disrupt the production of lamin A, and hence the structural integrity of the nuclear envelope, can also cause survivable syndromes such as mandibuloacral dysplasia (MAD). We report the first son of non-related Caucasian parents delivered via emergency LSCS at 34 weeks following preeclampsia, gestational diabetes and polyhydramnios. Extraction was difficult due to arthrogryposis. At birth (weight 1.65 kg), he showed the typical features of RD. Genetic testing revealed a homozygous pathogenic ZMPSTE24 frameshift variant c.1085dup p. (Leu362PhefsTer19) previously reported in mandibuloacral dysplasia (Agarwal AK, Fryns JP, Auchus RJ, Garg A. Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum Mol Genet 2003;12:1995-2001). Parents were heterozygous carriers. The baby received palliative care and died on day 2. The longest survival in RD is 120 days, in contrast to other laminopathies. Similar or identical mutation within the LMNA gene produces varied phenotypes which expands the spectrum. Currently, there is no curative therapy for RD. Our main aim to diagnose this condition is to offer counselling, genetic testing for future pregnancies, prevent unnecessary interventions and support the family through compassion and dignity.

Restrictive dermopathy is a lethal autosomal recessive disease characterized by tightly adherent skin, distinctive facial dysmorphisms, arthrogryposis, and pulmonary hypoplasia. While clinical findings are unique, histopathology and genetic analysis are critical for early diagnostic confirmation and to initiate appropriate management for this lethal disease. We report on a preterm Hutterite male neonate with biallelic ZMPSTE24 mutations to highlight the clinical and histopathological features of restrictive dermopathy and share our skin-directed management strategies.