RESUMO
BACKGROUND: Mandibuloacral Dysplasia with type B lipodystrophy (MADB) is a rare premature aging disorder with an autosomal recessive inheritance pattern. MADB is characterized by brittle hair, mottled, atrophic skin, generalized lipodystrophy, insulin resistance, metabolic complications and skeletal features like stunted growth, mandibular and clavicular hypoplasia and acro-osteolysis of the distal phalanges. MADB is caused by reduced activity of the enzyme zinc metalloprotease ZMPSTE24 resulting from compound heterozygous or homozygous mutations in ZMPSTE24. METHODS: In 2012, and again in 2018, eight related patients from the remote tropical rainforest of inland Suriname were analysed for dysmorphic features. DNA analysis was performed and clinical features were documented. We also analysed all previously reported genetically confirmed MADB patients from literature (n = 12) for their clinical features. Based on the features of all cases (n = 20) we defined major criteria as those present in 85-100% of all MADB patients and minor criteria as those present in 70-84% of patients. RESULTS: All the Surinamese patients are of African descent and share the same homozygous c.1196A > G, p.(Tyr399Cys) missense variant in the ZMPSTE24 gene, confirming MADB. Major criteria were found to be: short stature, clavicular hypoplasia, delayed closure of cranial sutures, high palate, mandibular hypoplasia, dental crowding, acro-osteolysis of the distal phalanges, hypoplastic nails, brittle and/or sparse hair, mottled pigmentation, atrophic and sclerodermic skin, and calcified skin nodules. Minor criteria were (generalized or partial) lipoatrophy of the extremities, joint contractures and shortened phalanges. Based on our detailed clinical observations, and a review of previously described cases, we propose that the clinical diagnosis of MADB is highly likely if a patient exhibits ≥4 major clinical criteria OR ≥ 3 major clinical criteria and ≥ 2 minor clinical criteria. CONCLUSIONS: We report on eight related Surinamese patients with MADB due to a homozygous founder mutation in ZMPSTE24. In low-income countries laboratory facilities for molecular genetic testing are scarce or lacking. However, because diagnosing MADB is essential for guiding clinical management and for family counselling, we defined clinical diagnostic criteria and suggest management guidelines.
Assuntos
Anormalidades Craniofaciais/genética , Lipodistrofia/genética , Proteínas de Membrana/genética , Metaloendopeptidases/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Homozigoto , Humanos , Masculino , Mutação/genética , Linhagem , Fenótipo , Suriname , Adulto JovemRESUMO
OBJECTIVE: To determine whether the increase in the percentage of stunted growth in Bush Negro infants in the interior of Surinam is related to an absolute food (i.e. energy) shortage or to a shortage of protein. DESIGN: Descriptive. METHOD: In the villages of Dan and Botopasi, children aged 2-5 years from two schools and their mothers were examined. Growth during the first year of life, duration of breastfeeding, age of introduction of and composition of complementary feeding and current nutritional status of mother and child were determined. RESULTS: Sixteen children and their mothers were included. Compared to the Dutch growth charts, birth weight was significantly lower (p = 0.03). After the age of 6 months there was a significant dropping off in weight gain (p = 0.018). Five of the 16 children received protein-poor complementary feeding, which did not lead to catch-up growth. Between the ages of 2-5, 6 of the 16 children showed stunted growth but none of the children or their mothers was wasted. Five of the 16 mothers had a body mass index > 25. CONCLUSION: The nutritional status of the mothers showed that there was no absolute shortage of energy. The protein content coming from the complementary food for the Bush Negroes in our research group was below recommended levels. Stunted growth in these children is better explained by a shortage of well-balanced complementary feeding rather than by an absolute shortage of energy. Education about food recommendations for the young child is of great importance in the prevention of chronic malnutrition.