Dual Molecular Diagnoses of Recessive Disorders in a Child from Consanguineous Parents: Case Report and Literature Review.

The widespread use of whole exome sequencing (WES) resulted in the discovery of multilocus pathogenic variations (MPV), defined as two or more distinct or overlapping Mendelian disorders occurring in a patient, leading to a blended phenotype. In this study, we report on a child with autosomal recessive primary microcephaly-5 (MCPH5) and nephropathic cystinosis. The proband is the first child of consanguineous parents, presenting a complex phenotype including neurodevelopmental delay, microcephaly, growth restriction, significant delay of bone maturation, lissencephaly, and abnormality of neuronal migration, photophobia, and renal tubular acidosis. WES revealed two pathogenic and homozygous variants: a c.4174C>T variant in the ASPM gene and a c.382C>T variant in the CTNS gene, explaining the complex phenotype. The literature review showed that most of the patients harboring two variants in recessive disease genes are born to consanguineous parents. To the best of our knowledge, the patient herein described is the first one harboring pathogenic variants in both the ASPM and CTNS genes. These findings highlight the importance of searching for MPV in patients with complex phenotypes investigated by genome-wide testing methods, especially for those patients born to consanguineous parents.

Cristales oportunos: cistinosis nefropática. Reporte de caso / Timely cristals: nephropathic cystinosis. Case report

Objetivo: Describir el caso clínico de un paciente con Cistinosis Nefropática diagnosticado a muy temprana edad. Método: Reporte de caso. Resultados: Se reporta el caso de una paciente de 7 meses de edad, quien consulta con poliuria, piolidipsia, glucosuria y bajo peso para la edad. De acuerdo a protocolos de evaluación interdisciplinaria establecidos con el servicio de Pediatría se logra evidenciar hallazgos oculares que orientan al diagnóstico final de la paciente. Conclusión: La Cistinosis es una enfermedad rara, cursa con manifestaciones oculares que podrían orientar un diagnóstico temprano e incluso predecir la severidad de la enfermedad y brindar la posibilidad de un tratamiento temprano. Es importante establecer protocolos interdisciplinarios, de apoyo diagnóstico, ante la sospecha de enfermedades sistémicas con posible compromiso ocular, en lugar de desistir ante la dificultad para valorar a los niños en la consulta de oftalmología, sobre todo en aquellos menores de un año. Se demuestra este caso con fines académicos teniendo en cuenta la baja incidencia de la enfermedad, pero también para destacar la importancia de contar con protocolos de atención interdisciplinaria ante la sospecha de enfermedades metabólicas en todas las edades.

Purpose: To describe a case of an infant with Nephropathic Cystinosis and the ocular fi ndings that leads to the diagnosis. Method: Case report. Results: Th is report describe a prompt and accurate diagnosis of a 7 months old patient, who consults with polyuria, piolidipsia, glucosuria and low weight. According to interdisciplinary evaluation protocols previusly established with Pediatrics services, it was possible to demonstrate ocular fi ndings of the disease, guiding the physician to the fi nal diagnosis. Conclusion: Cystinosis is a rare disease, its clinical presentation has ocular manifestations that could guide diagnosis and even predict its severity, off ering the possibility of an early treatment. When one suspect a systemic disease, It is important to establish interdisciplinary protocol, instead of surrendering to the challenge of an ophthalmological examination of an infant. We choose this case due to its low incidence, but also to highlight the importance of having interdisciplinary care protocols when a metabolic disease is suspected.

CTNS gene analysis emphasizes diagnostic value of eye examination in patients with cystinosis.

Classic nephropathic cystinosis (CNC) is an autosomal recessive and infrequent inborn metabolic disease that should be suspected in all children who show failure to thrive and renal Fanconi syndrome (RFS). Slit-lamp examination reveals pathognomonic corneal deposits of cystine crystals in virtually all affected individuals after 12-16 mo of age. A diagnosis of CNC is difficult to confirm in children living in Mexico and most Latin American countries, because cystine levels can be measured only at a few locations. We report the cystinosin genotype findings in 15 Latin American patients with a high clinical suspicion of CNC mainly due to RFS (n =13), although five of them lacked proper ophthalmologic assessment, despite being more than 1-year-old. Molecular analysis confirmed diagnosis of CNC in six (40%) of the 15 patients, five of them with RFS and cystine crystals. The remaining nine (60%) patients had a normal genotype. The predominance of a normal cystinosin genotype in eight of 13 patients with RFS (61.50%) reinforces the need to perform slit-lamp examinations in all patients with RFS over 1 yr of age, prior to measuring cystine or performing molecular cystinosin study, both methods not readily available throughout Latin America.