A New Case of PCSK1 Pathogenic Variant With Congenital Proprotein Convertase 1/3 Deficiency and Literature Review.
J Clin Endocrinol Metab
; 104(4): 985-993, 2019 04 01.
Article
en En
| MEDLINE
| ID: mdl-30383237
ABSTRACT
Issue To report a homozygous pathogenic variant in PCSK1 in a boy affected with proprotein convertase 1/3 (PC1/3) deficiency. Case Description and Literature Review A male infant born to consanguineous Turkish parents presented in the first week of life with transient central diabetes insipidus, watery diarrhea, micropenis due to hypogonadotropic hypogonadism and GH deficiency, and transient asymptomatic hypoglycemia. Further endocrine defects gradually appeared, including central hypothyroidism and mild central hypocortisolism (at 1 year), central diabetes insipidus that reappeared progressively (at 2.5 years), and obesity (at 2 years). Whole-exome sequencing revealed a homozygous nonsense pathogenic variant (NM_000439.4) c. 595 C>T in exon 5 of PCSK1, not yet reported in cases of PC1/3 deficiency. To date, 26 cases of PC1/3 deficiency have been reported in the literature. All individuals had early and severe malabsorptive diarrhea and 83% had polyuria-polydipsia syndrome (before 5 years). Most (79%) had early onset obesity. Various endocrine disorders were present, including GH deficiency (44%), mild central hypothyroidism (56%), central hypogonadism (44%), central hypocortisolism (57%), and postprandial hypoglycemia (52%). When described (n = 15), proinsulin levels were consistently high between 8 and 154 times the upper limit of normal (mean 74). Conclusion:
We described a homozygous nonsense pathogenic variant (NM_000439.4) c. 595 C>T in exon 5 of PCSK1 in a boy with congenital PC1/3 deficiency. Elevated proinsulin could be useful in the diagnosis of this condition.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_diarrhea
Asunto principal:
Proinsulina
/
Enfermedades Raras
/
Proproteína Convertasa 1
/
Enfermedades del Sistema Endocrino
/
Obesidad
Tipo de estudio:
Diagnostic_studies
Límite:
Child, preschool
/
Humans
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia