Researchers have diagnosed an infant with two rare conditions, Sanfilippo syndrome type B and skeletal dysplasia, using a genetic technique that examines all protein-coding genes in the body’s cells.
The finding underlines the value of using genome sequencing for precise diagnostics, particularly in rare and complex diseases.
The study “Mucopolysaccharidosis IIIB and mild skeletal anomalies: coexistence of NAGLU and CYP26B1 missense variations in the same patient in a Chinese family” was published in the journal BMC Medical Genetics.
A Chinese newborn (10 days) was admitted to the hospital with symptoms of limb rigidity, pulling up with head lag and frequent convulsions. Examinations revealed excessive spinal curvature, muscle stiffness, skull deformity, and umbilical and inguinal hernia — soft out-pouching around the belly-button and the abdomen. Video-encephalogram examinations also revealed progressive decline in brain activity.
Laboratory tests for cerebrospinal fluid, blood and urine were normal, and were negative for metabolic disorders. According to his symptoms, the infant was diagnosed with epilepsy and early onset epileptic encephalopathy.
The parents already had a newborn daughter who presented skull deformities and died soon after birth, which raised suspicions of a family history of genetic disorders.
To provide a more precise diagnosis, researchers sequenced the genome of the child and the parents using a technique called whole exome sequencing, which targets all the genes in our cells that code for proteins.
Disease-causing mutations, with genetic variations not previously observed, were found in two genes: NAGLU (responsible for Sanfilippo type B) and CYP26B1 (associated with skeletal dysplasia). a group of rare bone and cartilage disorders that affect the fetus’ skeleton.
Both parents carried the genetic mutations found in the child, as did his deceased sister (whose blood samples had been preserved for examination), confirming their inheritance.
The enzymatic activity of NAGLU was decreased greatly in the patient, confirming that the mutations disturbed NAGLU function.
Considering his genetic profile and symptoms, the infant was given a definite diagnosis of Sanfilippo type B and skeletal dysplasia. However, his disease manifestations were quite different from those characteristic for each disease and consisted more in combinations of the two.
The presence of these two rare conditions in the same patient is very unlikely and could be indicated only by using whole exome sequencing, reinforcing the utility of genome sequencing for diagnosis, particularly in rare and complex conditions.
The development of genome sequencing has made genetic testing more convenient. “When encountering a rare disease of unknown origin, we should perform a comprehensive genetic test to confirm the diagnosis,” researchers wrote.