Introduction:Congenital adrenal hyperplasia (CAH) is the most common cause of primary adrenal insufficiency. It is a
rare monogenic recessive disorder. In African setting in absence of neonatal
screening, the diagnosis is still late, based on a clinical approach. During
this clinical enquiry, information from past history or pedigree of the patient
is of a huge importance and may revealed surprises.Patients and Methods: In this observational study, we retrospectively
included all patients with a diagnosis of CAH. The diagnosis of CAH was
retained based on a high 17 hydroxyprogesterone level in addition to clinical
and morphological findings. From patients’ files, we extracted data on family history of disease, pedigree, clinical
findings and genetics when available of 39 patients from two
endocrinopeadiatric centers. Results: In 13 (30%) families, we found 20 reported deaths of
infant less than 12 months. In these 13 families, half of the patients followed
had 21 hydroxylase deficiencies and had 11
hydroxylase deficiencies. Unsurprisingly, we suspected adrenal
insufficiency in these patients at verbal autopsy even in families with a
patient with 11 hydroxylase deficiency. Other
non DSD malformations or genetic disorders with apparently no link with
CAH were reported in 3 families. The father of a patient reported to have
hypospadias. Conclusion: Each diagnosis of CAH made in our context is visible part of an iceberg.
Behind a diagnosis of CAH made in our setting, is a long course of care, a
dramatic past history revealing access to appropriate care disparity. Neonatal
screening should thus be considered as an emergency.
References
[1]
Auer, M.K., Nordenström, A., Lajic, S. and Reisch, N. (2023) Congenital Adrenal Hyperplasia. Lancet, 401, 227-244. https://doi.org/10.1016/S0140-6736(22)01330-7
[2]
El-Maouche, D., Arlt, W. and Merke, D.P. (2017) Congenital Adrenal Hyperplasia. Lancet, 390, 2194-210. https://doi.org/10.1016/S0140-6736(17)31431-9
[3]
Narasimhan, M.L. and Khattab, A. (2019) Genetics of Congenital Adrenal Hyperplasia and Genotype-Phenotype Correlation. Fertility and Sterility, 111, 24-29.
https://doi.org/10.1016/j.fertnstert.2018.11.007
[4]
Abdullah, M.A., Saeed, U., Abass, A., Lubna, K., Weam, A., Ali, A.S. and Elmwla, I.F. (2012) Disorders of Sex Development among Sudanese Children: 5-Year Experience of a Pediatric Endocrinology Unit. Journal of Pediatric Endocrinology and Metabolism, 25, 1065-1072. https://doi.org/10.1515/jpem-2011-0467
[5]
Sap Ngo Um, S., Mbono Betoko, R., Mekone, I., Bodieu Chetcha, A., Tardy, V., Dahoun, S., Mure, P.Y, Plotton, I., Etoa Etoga, M., Tony, J., Moifo, B., Muaf Tambo, F., Sobngwi, E. and Koki Ndomb, P.O. (2022) Clinical, Biochemical and Biomolecular Aspects of Congenital Adrenal Hyperplasia in a Group of Cameroonian Children and Adolescents. Journal of Pediatric Endocrinology and Metabolism, 35, 777-783. https://doi.org/10.1515/jpem-2021-0696
[6]
WHO (2007) Verbal Autopsy Standards: Ascertaining and Attributing Cause of Death. WHO, Geneva, 117.
[7]
Snow, R.W., Amstrong, J.R., Foster, D., Winstanley, M.T., Marsh, V.M., Newton, C.R., et al. (1992) Childhood Death in Africa: Uses and Limitations of Verbal Autopsies. Lancet, 340, 351-356. https://doi.org/10.1016/0140-6736(92)91414-4
[8]
Rushworth, R.L., Torpy, D.J., Stratakis, C.A. and Falhammar, H. (2018) Adrenal Crises in Children: Perspectives and Research Directions. Hormone Research in Paediatrics, 89, 341-351. https://doi.org/10.1159/000481660
[9]
Ali, S.R., Bryce, J., Haghpanahan H., Lewsey, J.D., Tan, L.E., Atapattu, N., Birkebaek, N.H., Blankenstein, O., Neumann, U., Balsamo, A., Ortolano, R., Bonfig, W., Claahsen-van der Grinten, H.L., Cools, M., Costa, E.C., Darendeliler, F., Poyrazoglu, S., Elsedfy, H., Finken, M.J.J., Fluck, C.E., Gevers, E., Korbonits, M., Guaragna-Filho, G., Guran, T., Guven, A., Hannema, S.E., Higham, C., Hughes, I.A., Tadokoro-Cuccaro, R., Thankamony, A., Iotova, V., Krone, N.P., Krone, R., Lichiardopol, C., Luczay, A., Mendonca, B.B., Bachega, T.A.S.S., Miranda M.C., Milenkovic, T., Mohnike, K., Nordenstrom, A., Einaudi, S., van der Kamp, H., Vieites, A., de Vries, L., Ross, R.J.M. and Ahmed, S.F. (2021) Real-World Estimates of Adrenal Insufficiency-Related Adverse Events in Children with Congenital Adrenal Hyperplasia. Journal of Clinical Endocrinology & Metabolism, 106, e192-e203.
https://doi.org/10.1210/clinem/dgaa694
[10]
Kopacek, C., de Castro, S.M., Prado, M.J., da Sylva, C.M., Beltrao, L.A. and Spritzer, P.M. (2017) Neonatla Screening in Southern Brazil: A Population Based Study with 108,409 Infants. BMC Pediatrics, 17, 22. https://doi.org/10.1186/s12887-016-0772-x
[11]
Güran, T., Tezel, B., Gürbüz, F., Selver Eklioglu, B., Hatipoglu, N., Kara, C., Simsek, E., Cizmecioglu, F.M., Ozon, A., Bas, F., Aydin, M. and Darendeliler, F. (2019) Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: A Pilot Study with 38,935 Infants. Journal of Clinical Research in Pediatric Endocrinology, 11, 13-23.
https://doi.org/10.4274/jcrpe.galenos.2018.2018.0117
[12]
Serino, D., Camassei, F.D., Delalande, O., Marras, C.E., Specchio, N., Vigevano, F. and Fusco, L. (2014) Hemiconvulsion-Hemiplegia-Epilepsy Syndrome Associated with Inflammatory-Degenerative Hystopathological Findings in Child with Congenital Adrenal Hyperplasia. European Journal of Paediatric Neurology, 18, 416-419.
https://doi.org/10.1016/j.ejpn.2013.11.001
[13]
Abe, Y., Sakai, T., Okumura, A., Akaboshi, S., Fukuda, M., Haginoya, K., Hamano, S., Hirano, K., Kikuchi, K., Kubota, M., Lee, S., Maegaki, Y., Sanefuji, M., Shimozato, S., Suzuki, M., Suzuki, Y., Takahashi, M., Watanabe, K., Mizuguchi, M. and Yamanouchi, H. (2016) Manifestations and Characteristics of Congenital Adrenal Hyperplasia-Associated Encephalopathy. Brain and Development, 38, 638-647.
https://doi.org/10.1016/j.braindev.2016.01.007